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Citalopram versus other anti-depressive agents for depression

  1. Andrea Cipriani1,*,
  2. Marianna Purgato1,
  3. Toshi A Furukawa2,
  4. Carlotta Trespidi1,
  5. Giuseppe Imperadore1,
  6. Alessandra Signoretti1,
  7. Rachel Churchill3,
  8. Norio Watanabe4,
  9. Corrado Barbui1

Editorial Group: Cochrane Common Mental Disorders Group

Published Online: 11 JUL 2012

Assessed as up-to-date: 1 FEB 2012

DOI: 10.1002/14651858.CD006534.pub2


How to Cite

Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, Churchill R, Watanabe N, Barbui C. Citalopram versus other anti-depressive agents for depression. Cochrane Database of Systematic Reviews 2012, Issue 7. Art. No.: CD006534. DOI: 10.1002/14651858.CD006534.pub2.

Author Information

  1. 1

    University of Verona, Department of Public Health and Community Medicine, Section of Psychiatry, Verona, Italy

  2. 2

    Kyoto University Graduate School of Medicine / School of Public Health, Department of Health Promotion and Human Behavior, Kyoto, Japan

  3. 3

    University of Bristol, Academic Unit of Psychiatry, School of Social and Community Medicine, Bristol, UK

  4. 4

    Nagoya City University Graduate School of Medical Sciences, Department of Psychiatry & Cognitive-Behavioral Medicine, Nagoya, Aichi, Japan

*Andrea Cipriani, Department of Public Health and Community Medicine, Section of Psychiatry, University of Verona, Policlinico "G.B.Rossi", Piazzale L.A. Scuro, 10, Verona, 37134, Italy. andrea.cipriani@univr.it. andrea.cipriani@psych.ox.ac.uk.

Publication History

  1. Publication Status: New
  2. Published Online: 11 JUL 2012

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Characteristics of included studies [ordered by study ID]
29060/785

MethodsSix-week, double-blind, placebo-controlled, multicentre, parallel group, randomised study.


ParticipantsPatients with major depressive disorder (DSM-IV criteria), with a Montgomery and Asberg Depression Rating Scale (MADRS) score of at least 17 (both at the screening and baseline visits).

Exclusion criteria: patient who have taken other psychotropic drugs, had a history of schizophrenia or schizoaffective disorder, had current (or within 6 months prior to screening) Axis I anxiety disorder or Axis I affective disorder other than major depressive disorder. Patient who, in the investigator's judgement, posed a current homicidal or suicidal risk. Women who had a positive pregnancy test or who were lactating, women of child-bearing potential who were not practicing a clinically accepted method of contraception. Patient with a serious medical disorder or condition that, in the investigator's opinion, precluded the administration of paroxetine controlled release (CR) or citalopram. Patient undergoing any form of psychotherapy.

Age range: 18-65 years.


InterventionsCitalopram 20 mg/day: 107 participants

Citalopram 40 mg/day: 100 participants

Paroxetine CR 12.5 mg/day: 96 participants

Paroxetine CR 25 mg/day: 103 participants

Placebo: 105 participants


OutcomesPrimary outcome: proportion of MADRS responders at the week 6 (last observation carried forward at endpoint). Response was defined as reduction of 50% or more in the MADRS total score, relative to the baseline total score.

Secondary outcomes: mean change from baseline in the MADRS total score; proportion of subjects with a positive response (score of 1 or 2) on the global improvement rating of the Clinical Global Impression (CGI); mean change from baseline in Hamilton Anxiety Rating Scale (HAM-A) total score; mean change from baseline in CGI severity of illness rating; mean change from baseline in Hospital Anxiety and Depression Scale (HAD) total score; mean change from baseline in HAD, Anxiety and Depression sub-scales and mean change from baseline in Sheehan Disability Scale (SDS) total score. Safety was assessed via adverse event monitoring, vital signs, laboratory evaluation, serum pregnancy test, ECGs, physical exam and weight.


NotesThis study was funded by GSK (paroxetine manufacturer).

One death for suicide in the placebo group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Subjects were randomized (1:1:1:1:1) to either paroxetine CR 12.5 mg, paroxetine CR 25 mg, citalopram 20 mg, citalopram 40 mg, or placebo".

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "paroxetine CR and citalopram were provided as over-encapsulated tablets (...) placebo capsules were identical in appearance to the active study medication capsules".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "all subjects who were randomized to double-blind medication and had at least one valid post baseline efficacy assessment comprised the Intention-to-treat (ITT) efficacy population. The Last Observation Carried Forward (LOCF) data at week 6 were the primary dataset of interest".

Selective reporting (reporting bias)High riskRemission rate are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Allard 2004

MethodsTwenty-two-week, double-blind, randomised, parallel group study.


ParticipantsOutpatients meeting DSM-IV criteria for major depression, having a minimum score of 20 on Montgomery and Asberg Depression Rating Scale (MADRS) and a ≤ 20% change in MADRS score between pre-study and baseline visits, which were one-week apart.

Age-range: 64-89 years


InterventionsVenlafaxine: 76 participants.

Citalopram: 75 participants

Venlafaxine dose range: 75-150 mg/day

Citalopram dose range: 20-40 mg/day

Zopiclone (≤ 7.5 mg/day) or zolpidem (≤ 5 mg/day) for insomnia and medications for treatment of somatic disorders were allowed.


OutcomesPrimary outcome: change in MADRS score from baseline to week 8.

Secondary outcomes: Clinical Global Impression (CGI), subscale Severity of Illness and Global Improvement.

Geriatric Depression Scale (GDS-20).


NotesThis study was funded by Wyeth (venlafaxine manufacturer).

One death in the citalopram group (unknown cause of death).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "the study was designed as a randomized". Probably done.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "both venlafaxine and citalopram were administered orally in identically appearing capsules to maintain the double-blind integrity of the study".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskEven though an Intention-to-treat (ITT) approach was used, no reliable information was provided in the paper to check the consistency between methods and results (for instance, see figures in  Table 1 of the published paper).

Quote: "Analyses of the efficacy variables were performed on an ITT patient population, defined as all randomised patients who had received at least one dose of study medication and with at least one efficacy evaluation while on treatment [...] In case of missing values at 8 or 22 weeks, the last prior on-therapy value was carried forward (LOCF). Analyses of safety were performed on all patients who had received at least one dose of study medication."

Selective reporting (reporting bias)High riskNo clear data about dropout rate in each group. Quote: "There were 33 withdrawals, nine of which due to adverse events (...). 118 patients completed the 6-month study...".

Other biasUnclear riskSponsorship bias cannot be ruled out.

Andersen 1986

MethodsFive-week controlled, double-blind, multicentre study


ParticipantsIn-patients having a total score of ≥ 18 on the Hamilton Depression Rating Scale (HDRS) or a score of ≥ 9 on the Hamilton Depression Sub-scale (HDSS).

Exclusion criteria: patients with age below 19 or above 65 years, schizophrenia, paranoid psychoses, oligophrenia, organic brain syndrome, chronic drug or alcohol abuse or serious somatic disease, such as myocardial infarction within the last 6 months, acute glaucoma, severe liver disease, hypertension, endocrine disorder, etc...Patients treated with MAO inhibitors or tricyclic antidepressants within the last 3 weeks were also excluded. Other reasons for exclusion were pregnancy, current depressive episode of more than 12 months duration, and severe retardation or suicidal behaviour (requiring ECT)


InterventionsCitalopram: 57 participants

Clomipramine: 57 participants

Citalopram: 40 mg/day

Clomipramine: 150 mg/day

Additional medication was restricted to oxazepam or nitrazepam as sedative/hypnotic. Other sedatives or neuroleptics were not allowed. Some patients received occasional doses of acetylsalicylic acid.


OutcomesPrimary outcome: change in HDRS and HDSS that is assumed to represent core symptoms in depressed patients.


NotesData on rating scale score at baseline are missing.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients meeting the inclusion criteria were stratified according to diagnostic rating (endogenous versus non- endogenous) and department before being randomly allocated in a double blind fashion to treatment with either citalopram or clomipramine for five weeks".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskInformation provided is "double blind", without clear description of method.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information provided.

Selective reporting (reporting bias)High riskData on rating scale score at baseline are missing. Information about side-effects are missing.

Other biasUnclear riskThis study was not sponsored by pharmaceutical industry.

Berlanga 2006

MethodsEight-week double-blind clinical trial.


ParticipantsPatients between 18 and 40 years, meeting the DSM-IV criteria for Major Depressive Disorder after two independent clinical interviews, and scoring at least 18 in the 21-item Hamilton Depression Rating Scale (HDRS).

Patients were excluded if psychotic symptoms were present or a history of past manic, hypomanic or mixed episodes was confirmed. Also participants with uncontrolled medical illnesses, evidence of drug abuse or severe personality disorders were not included. In the case of women individuals with irregular menstrual cycles, pregnancy, breastfeeding, current hormonal treatments and biological or surgical menopause were also excluded.


InterventionsCitalopram: 54 participants

Reboxetine: 47 participants

Citalopram dose range: 20-40 mg/day (mean dose: 25.8 SD 3.7).

Reboxetine dose range: 4-8 mg/day (mean dose: 5.8 SD 1.5)


OutcomesChange in HDRS scores from baseline to endpoint.


NotesThis study was funded by Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "subjects were randomly assigned to an 8-week double blind comparative trial with reboxetine or citalopram". Probably done.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "drugs were administered orally at bedtime using identical capsules containing 4 mg of reboxetine or 20 mg of citalopram as starting doses".

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "comparison were done only with patients having at least five evaluations (basal and four weeks of treatment). In patients who had a minimum of five evaluations but did not complete the 8-week of follow-up, Last Observation Carried Forward (LOCF) procedure was used.

Selective reporting (reporting bias)High riskContinous data about the two groups are missing. The paper reported only data for men or for women.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Bouchard 1987

MethodsSix-week multicentre, controlled, double-blind trial.


ParticipantsPatients who suffered from a depression which required drug treatment and which was of a severity corresponding to a total score of at least 15 on the Montgomery and Asberg Depression Rating Scale (MADRS) after a wash-out period of 3-7 days. The depression was classified as endogenous, doubtfully endogenous or non-endogenous, using the Newcastle rating scale and the DSM-III, as belonging to one of the following groups: major depressive episode with melancholia, major depressive episode without melancholia, atypical depression.

Exclusion criteria: pregnancy or absence of use of an effective contraceptive methods, severe somatic disease (particularly severe cardiac, renal or hepatic disease), organic brain syndrome, schizophrenia or paranoid psychosis, epilepsy, abuse of alcohol or narcotics, treatment with MAO-inhibitors within the last 3 weeks preceding entry into the trial, previous unsuccessful treatment with one of the test drugs, patient's refusal to participate in the trial.


InterventionsCitalopram: 48 participants

Maprotiline: 48 participants

Citalopram dose range: 40-60 mg/day

Maprotiline dose range: 75-150 mg/day

Among psychotropic drugs, only benzodiazepines were allowed.


OutcomesPrimary outcome: mean score on MADRS or Clinical Global Impression (CGI).


NotesThis study was funded Lundbeck (citalopram manufacturer).

One death for suicide in the citalopram group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "the patients were allocated at random in blocks of four to double-blind treatment with either citalopram or maprotiline once daily for a period of 6 weeks". Probably done.

Allocation concealment (selection bias)Unclear riskNo data provided

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "Using the double- dummy half patients received active citalopram tablets and placebo maprotiline tablets and the other half was given placebo citalopram tablets and active maprotiline tablets". Probably done.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo clear data provided

Selective reporting (reporting bias)High riskCGI-S score at baseline are missing. Remission rate are reported only at endpoint (week 1-4 are missing).

Other biasUnclear riskSponsorship bias cannot be ruled out.

Bougerol 1997a

MethodsEight-week double-blind, multicentre study in a psychiatrist setting.


ParticipantsIn- and outpatients fulfilling DSM-III-R criteria for a major depressive disorder or bipolar disorder. The severity of depression should be 25 or more on the Montgomery and Asberg Depression Rating Scale (MADRS).
Age range: 18-65 years old.
Exclusion criteria: pregnancy, lactation, failure to use a safetable contraceptive method, alcohol or drug abuse within the last year, patients with severe somatic, neurologic or psychiatric disease, treatment with MAOI within 2 weeks prior to entry the trial, hypersensitivity to study drugs, suicide risk.


InterventionsFluoxetine: 158 participants.
Citalopram: 158 participants.
Fluoxetine dose: 20 mg.
Citalopram dose range: 20-40 mg/day.
Concomitant psychotropic medication was prohibited, but use of benzodiazepines for insomnia was allowed.


OutcomesPrimary outcome: MADRS.
Secondary outcomes: Hamilton Depression Rating Scale (HDRS-17), Clinical Global Impression (CGI).


NotesThree attempted suicides in citalopram group, and three attempted suicides in fluoxetine group.

This study was funded Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo clear data provided

Allocation concealment (selection bias)Unclear riskNo data provided

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "due to the different appearance of the two drugs the "double-dummy" principle was used to blind the study".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "patients populations were defined as the Intention-to-treat (ITT) group and the Efficacy (EFF) group. The ITT population comprised all randomized patients. The EFF population consisted of all patients who fulfilled the entry criteria and had completed at least 14 days double-blind treatment. All efficacy analyses were made on the basis of the EFF population".

Selective reporting (reporting bias)High riskSome endpoint scores and baseline scores are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Bougerol 1997b

MethodsEight-week, double-blind, multicentre, parallel group study in general practice.


ParticipantsOutpatients (primary care) fulfilling DSM-III-R criteria for a major depressive disorder. The severity of depression should be 22 or more on the Montgomery and Asberg Depression Rating Scale (MADRS).
Age range: 18-70 years.

Exclusion criteria: pregnancy, lactation, failure to use a safetable contraceptive method, alcohol or drug abuse within the last year, patients with severe somatic, neurologic or psychiatric disease, treatment with MAOI within two weeks prior to entry the trial, hypersensitivity to study drugs, suicide risk.


InterventionsFluoxetine: 184 participants.
Citalopram: 173 participants.
Fluoxetine dose: 20 mg.
Citalopram dose: 20 mg/day.
Concomitant psychotropic medication was prohibited, but use of benzodiazepines for insomnia.


OutcomesPrimary outcome: MADRS.
Secondary outcomes: Hamilton Rating Scale for Depression (HDRS-17), Clinical Global Impression (CGI).


NotesThis study was funded Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomized to double blind treatment". Probably done.

Allocation concealment (selection bias)Unclear riskNo data provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "due to the different appearance of the two drugs the "double-dummy" principle was used to blind the study".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: " patients populations were defined as the Intention-to-treat (ITT) group and the Efficacy (EFF) group. The ITT population comprised all randomized patients. The EFF population consisted of all patients who fulfilled the entry criteria and had completed at least 14 days double-blind treatment. All efficacy analyses were made on the basis of the EFF population".

Selective reporting (reporting bias)Unclear riskSome endpoint scores and baseline scores are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Burke 2002

MethodsEight-week, double-blind, randomised, parallel group, multicentre study.


ParticipantsOutpatients meeting DSM-IV criteria for Major Depressive Disorder, having a minimum score of 22 on Montgomery-Asberg Depression Rating Scale (MADRS) and a minimum score of 2 on Item 1 of Hamilton Depression Rating Scale (HDRS).
Age range: 18-65 years.
Exclusion criteria: any DSM-IV Axis I disorder other than major depression, any personality disorder, a history of substance abuse, a suicide attempt within the past year or evidence of active suicidal ideation (as indicated by a score of at least 5 on item 10 of the MADRS), pregnancy, lactation, women of childbearing potential if they didn't agree to use a medically acceptable method of contraception, concomitant psychotropic medication.


InterventionsEscitalopram: 252 participants.
Citalopram: 127 participants.
Escitalopram dose range: 10-20 mg/day.
Citalopram dose: 40 mg/day.
Zolpidem for insomnia was allowed (no more than three times per week).


OutcomesPrimary Outcome: Change from baseline to week 8 in MADRS, HDRS-24, HDRS Depressed Mood Item, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S).
Secondary Outcomes: change in Hamilton Rating Scale for Anxiety (HAM-A), Center for Epidemiological Studies-Depression Scale (CES-D), Quality of Life Questionnaire (QOL) and a 16-item instrument derived from the QOL enjoyment and satisfaction questionnaire from baseline to endpoint.


NotesThis study was funded by escitalopram manufacturer.

One suicide attempted in escitalopram 20 mg group. One intentional overdose in placebo group. One non-intentional overdose in citalopram 40 mg group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients meeting eligibility criteria at a screening visit entered a 1-week, single blind, placebo lead-in period, returning for a baseline visit at the end of the lead-in period. Patients completing the placebo lead-in, who continued to meet all entry criteria, were then randomly assigned to receive 8 weeks of double blind treatment".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "in order to maintain the blind, all double blind study medication was administered as one capsule per day, regardless of dose of treatment group. No further adjustment of dosage was permitted".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Efficacy was assessed in the Intention-to-treat (ITT) population which included all patients who had received at least 1 dose of double blind study medication and had at least 1 post-baseline MADRS assessment".

Selective reporting (reporting bias)Low riskRemission rate are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Castanedo de Alba 1998

MethodsSix-week, open-label, controlled study.


ParticipantsForty-two patients of both sexes ranging in age from 18 to 65 years were included in this trial if they fulfilled the criteria of major depressive disorder according to the DSM-III-R and had a minimum score of 17 on Hamilton Depression Rating Scale 17 Item (HDRS-17). All patients gave their written informed consent.

The exclusion criteria were: patients with severe depression and suicidal tendencies, patients with psychotic symptoms, pregnant women, alcoholic or drug abuse patients, patients with epilepsy, with schizophrenia or other form of psychosis, patients with hepatic and/or renal disease, cardiac patients, patients with acquired immunodeficiency syndrome, with hepatitis or diabetes, patients who are been treated with other antidepressants within two weeks before the study, and patients with known hypersensitivity or resistance to citalopram or moclobemide.


InterventionsCitalopram: 22 participants.

Moclobemide: 20 participants.

Citalopram dose range: 20-60 mg/day (mean dose: 28.0 mg)

Moclobemide dose range: 300-600 mg/day (mean dose: 545 mg)


OutcomesPrimary Outcome: Change from baseline to week 6 in HDRS-17.


NotesThis study was not sponsored by pharmaceutical industry.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomly allocated to two groups..."

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
High riskQuote: "this was an open label study..."

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "data from patients who withdrew from the study were not taken into account for the final analysis and were considered only for the statistical analysis of adverse reactions".

Selective reporting (reporting bias)Unclear riskResponse rate and remission rate are missing.

Other biasUnclear riskThis study was not sponsored by pharmaceutical industry.

Colonna 2005

MethodsTwenty-four-week, double-blind, randomised, parallel group, multicentre study.


ParticipantsOutpatients meeting DSM-IV criteria for Major Depressive Disorder, having a total score between 22 and 40 on Montgomery-Asberg Depression Rating Scale (MADRS).
Age range: 18-65 years.
Exclusion criteria: other serious illnesses on the basis of medical history and the screening results of a physical examination, electrocardiogram (ECG) and clinical laboratory tests, pregnancy, breast-feeding, non adequate contraception at time of screening, mania or any bipolar disorder, schizophrenia or any psychotic disorder, obsessive-compulsive disorder, eating disorders, mental retardation or any pervasive developmental or cognitive disorder, MADRS score >= 5 on item 10, concomitant treatment with antipsychotics, antidepressants, hypnotics, anxiolytics, antiepileptics, barbiturates, chloral hydrate, 5-HT receptor agonists, electroconvulsive treatment, behaviour therapy or psychotherapy, use of any investigational drug within the past 30 days, history of schizophrenia, psychotic disorder or drug abuse, history of severe drug allergy or hypersensitivity (including to citalopram), a lack of response to more than one antidepressant treatment (including citalopram) during the present depressive episode.


InterventionsEscitalopram: 175 participants.
Citalopram: 182 participants.
Escitalopram dose: 10 mg/day.
Citalopram dose: 20 mg/day.
Benzodiazepines in low doses for insomnia were allowed.


OutcomesPrimary Outcome: Change from baseline in the mean of the MADRS during the 24 weeks.
Secondary Outcomes: MADRS single items, Clinical Global Impression - Improvement (CGI-I), Clinical Global Impression - Severity (CGI-S).


NotesThis study was funded by Lundbeck.

Three suicide attempted in citalopram group; three suicide attempted in escitalopram group.

Remission: a score equal or less than 12 on MADRS.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "There was an initial 1-week single-blind, placebo period, followed by randomization of patients in a 1:1 ratio to treatment (...). Patients were assigned to escitalopram or citalopram treatment according to a computer-generated randomization list drawn-up by Lundbeck".

Allocation concealment (selection bias)Low riskQuote: "The details of the randomization series were unknown to any of the investigators and were contained in a set of sealed opaque envelopes. At each study centre, sequentially enrolled patients were assigned the lowest randomization number available".

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "all study personnel and participants were blinded (...), the study products were tablets of identical appearance, taste and smell".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Intention-to-treat (ITT) population included all randomised patients who took at least one dose of double-blind study product and who had at least one valid post-baseline MADRS assessment."

Selective reporting (reporting bias)High riskMissing standard deviations.

Other biasUnclear riskSponsorship bias cannot be ruled out.

de Wilde 1985

MethodsSix-week controlled, double-blind, randomised trial.


ParticipantsIn-patients suffering from endogenous depression or chronic dysthymic disorder (Spitzer's research Diagnostic Criteria), with a total score of at least 25 on the 10-item Comprehensive Psychopathological Rating Scale (CPRS) sub-scale for depression.

Age range: 18-70 years

Exclusion criteria: pregnancy/lactation, serious somatic disease (particularly of the heart, liver or kidneys), organic brain syndrome, need for ECT, abuse of alcohol or drugs, and treatment with MAO inhibitors within the previous 3 weeks.


InterventionsCitalopram: 30 participants

Mianserin: 30 participants

Citalopram dose range: 40-80 mg/die

Mianserin dose range:60-120 mg/die

Additional medication with benzodiazepine as sedatives/hypnotics was permitted.


OutcomesPrimary outcome: mean change at endpoint on the 10-item CPRS sub-scale for depression and on Clinical Global Impression - Severity (CGI-S).


NotesThis study was funded by Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: " Patients were randomly allocated". Probably done.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "double blind treatment with either citalopram or mianserin, administered as identically looking capsules".

Incomplete outcome data (attrition bias)
All outcomes
High riskObserved-case (completers) analysis only

Selective reporting (reporting bias)High riskNo reliable data about response rate.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Ekselius 1997

MethodsTwenty four-week, double-blind, randomised multicentre study.


ParticipantsGeneral Practice patients fulfilling DSM-III-R criteria for major depression with a minimum baseline score of 21 on Montgomery-Asberg Depression Rating Scale (MADRS).
Age range: 18-70 years old.
Exclusion criteria: pregnancy, lactating, inadequate method of contraception, severe depression of psychotic dimension, history of serious suicide attempt or suicide risk, therapy refractory depression, previous treatment with sertraline or citalopram without significant effect, bipolar disorder, previous or present history of alcohol or drug abuse, history of epilepsy, known intolerance or allergic reactions to SSRIs, therapy with lithium within the preceding month, currently receiving and unable to discontinue any other psychotropic medication, except for a hypnotic for insomnia or a daytime anxiolytic, currently receiving treatment with cimetidine, warfarin or tryptophan, significant hepatic or renal disease, previous participation in the study. Patients who had been receiving antidepressants drugs required to have a washout period of at least 3 weeks.


InterventionsSertraline: 200 participants.
Citalopram: 200 participants.
Sertraline dose: 50-150 mg/day.
Citalopram dose: 20-60 mg/day.
Permitted Nitrazepam 2.5-10 mg/day, flunitrazepam 0.5-2 mg/day and oxazepam 15-25 mg/day.


OutcomesPrimary Outcome: change in MADRS, Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I).


NotesThis study was funded by Pfizer (sertraline manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "randomized". Probably done, as a similar trial by these investigators included the same phrase and used a proper method of allocation.

Allocation concealment (selection bias)Unclear riskInsufficient information.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "double-dummy" but we have no other information.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskMissing standard deviations on MADRS data.

Selective reporting (reporting bias)Unclear riskThe study protocol is not available.

Other biasUnclear riskInsufficient information to assess whether an important risk of bias exists.

Gastpar 2006

MethodsSix-week, double-blind, multicentre, placebo-controlled, randomised study.


ParticipantsOutpatients with a moderate depressive episode having depression with a score of 20-24 on the first 17 items of the 21-item Hamilton Depression Rating Scale (HDRS-21) and diagnosis of moderate depression (first manifestation or recurrent depressive disorder) defined by ICD-10 criteria or according to DSM-IV criteria for major depressive episode and recurrent major depression; females taking adequate contraceptive or without child-bearing potential.

Exclusion criteria: diagnosis of resistance to depression treatment, known schizophrenia, psychosis or dementia, depressive mood due to a serious general disease, known hypersensitivity to study medication, known photosensitivity, specific psychotherapy during the last two months or treatment with psychoactive drugs (antidepressants, neuroleptic drugs, anxiolytic drugs, etc...) during the last 3 weeks (6 weeks for fluoxetine) prior to study enrolment, and determined suicidal tendency by scores of > 2 in item 3 of HDRS-21 scale or known attempted suicide.


InterventionsCitalopram: 127 participants.

Hypericum extract STW3-VI: 131 participants.

Placebo: 130 participants.

Citalopram: 20 mg/day

Hypericum extract STW3-VI: 900 mg/day


OutcomesPrimary outcome: endpoint total score on HDRS.

Secondary outcomes: endpoint total score on the Von Zerssen's Adjective Mood Scale (BfS) and Clinical Global Impression (CGI) scale.


NotesThis study was funded by STW3-VI manufacturer (EPA EuroPharma).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "according to a randomization schedule using the randomization program IDV-Rancode 3.6, patients were chronologically randomized by the investigators to treatment groups by assigning them the lowest yet unassigned treatment number available at the trial centre".

Allocation concealment (selection bias)Unclear riskNo information reported.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "the double-dummy technique was used to guarantee complete blinding for both investigator and patient at any time in the trial".

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "the tests for superiority (STW3-VI over placebo) were carried out on the Intention-to-treat (ITT) population, the test for non-inferiority (of STW3-VI to citalopram) on the Per Protocol (PP) population."

Selective reporting (reporting bias)Unclear riskNo clear data about dropout rate in each group.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Gravem 1987

MethodsSix-week, double-blind, multicentre trial


ParticipantsIn- and out-patients who were referred to hospital for a depression requiring drug treatment. The patient's depression was classified as endogenous or non-endogenous by means of the Newcastle Depression Scale I.

Age range: 18-70 years

Exclusion criteria: serious physical disease, pregnancy, previous resistance to therapy with amitriptyline or citalopram in doses considered to be adequate.


InterventionsCitalopram: 27 participants

Amitriptyline: 24 participants

Citalopram dose range: 20-60 mg/day

Amitriptyline dose range: 75-225 mg/day

Additionally treatment was not allowed apart from low doses of diazepam or nitrazepam for severe anxiety or insomnia, if necessary.


OutcomesPrimary outcome: endpoint total score on the 10-item Comprehensive Psychopathological Rating Scale (CPRS) sub-scale for depression.


NotesThis study was funded by Lundbeck (citalopram manufacturer).

No signed informed consent was required, neither from the patient nor from his relatives. The clinician informed the patient of the object of the study and that he/she was quite free to participate. At that time there were no ethical committees in Norway to evaluate the design of study (Health Autorities approved the study).

One suicide attempted in citalopram group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo reliable information provided (no data about sequence generation).

Allocation concealment (selection bias)Unclear riskNo information reported.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "tablets of identical appearance were prepared".

Probably done.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information about incomplete data in each group.

Selective reporting (reporting bias)High riskNo MADRS scores were reported (neither at baseline nor at endpoint). Response rate and remission rate are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Hosak 1999

MethodsFour-week, randomised and open study.


ParticipantsHospitalised patients. Diagnoses for inclusion (according to the ICD-10 criteria) were: bipolar affective disorder, most recent episode depressed (8 participants); major depressive episode, single (44 participants), major depressive episode, recurrent (38 participants).

Average age: 44.5 years (SD14.3).


InterventionsCitalopram: 29 participants.

Amitriptyline: 31 participants.

Fluoxetine: 30 participants.

Citalopram dose range: 20-60 mg/day

Amitriptyline dose range: 150-300 mg/day

Fluoxetine: 20-60 mg/day


OutcomesPrimary Outcome: mean change on Hamilton Depression Rating Scale 21-item (HDRS-21).


NotesStudy report published only in Czech.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "the subjects were randomized to the study antidepressant using computer randomization program (Excel) at the beginning of the initial hospitalization at the Dpt. of Psychiatry in Hradec Kralovc."

Allocation concealment (selection bias)Unclear riskNo information reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo information reported.

Incomplete outcome data (attrition bias)
All outcomes
High riskNo information reported.

Selective reporting (reporting bias)Unclear riskNo information reported.

Other biasUnclear riskNo information reported.

Hsu 2011

MethodsSix-week, randomised, double-blind study.


ParticipantsOutpatients aged between 20 and 65 years, who met the DSM-IV criteria for MDD, experiencing a drug naive first depressive episode, exhibited a total score on the Montgomery-Asberg Depression Rating Scale (MADRS) (MADRS of > or = 25 at screening, and displayed a < or = 20% decrease in MADRS score between screening and baseline visits).

Patients were excluded from the trial if they had a history of severe allergy or major medical illness. Were also excluded patients who displayed acutely suicidal tendencies, or had a history of drug or alcohol dependence or abuse. In addition, patients were excluded if they had previously received treatment of any antidepressant or had taken monoamine oxidase inhibitors. Women who were pregnant, lactating, and women with childbearing potential who were not using a medically acceptable form of contraception were also excluded.


InterventionsCitalopram: 25 participants.

Sertraline: 26 participants.

Citalopram dose: 20 mg/day.

Setraline dose: 50 mg/day.


OutcomesPrimary outcomes: MADRS total score, response and remission rates.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomly assigned". Likely done

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "The primary efficacy end points were the mean difference in MADRS total score at baseline and weeks 1, 3, and 6. Other efficacy end points included the percentage of patients with MADRS remission (MADRS total scores e10) and response (Q50% reduction from randomization in MADRS total score) at treatment week 6. Tolerability was assessed as the percentage of patients who developed specific adverse events during the
treatment period."

Selective reporting (reporting bias)High riskMADRS scores were reported only in figures.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Karlsson 2000

MethodsTwelve-week, randomised, multicentre, double-blind study.


ParticipantsIn- or out-patients being treated in psychiatric hospitals, psychiatric specialist or general practices, or geriatrics units. Patients were to have a diagnosis of major depression (DSM-III-R criteria), a Montgomery and Asberg Rating Scale for Depression (MADRS) total score of ≥ 20 and a Mini Mental State Examination (MMSE) total score of at least 16. For patients with a MMSE score of 16-24, the DSM-III-R diagnosis forms for dementia were completed.

Exclusion criteria: patients having schizophrenia or related psychotic disorder, neurological disease other than vascular or primary degenerative dementia, focal cortical deficit or chronic drug or alcohol abuse. Patients with severe somatic disorders, such as cardiac, renal, hepatic or endocrinological disorders or blood laboratory abnormalities, which, in the opinion of investigator, interfered with participation in the study. Patients were not to have received other antidepressants during previous 4-7 days; irreversible MAO-inhibitors (A or B), lithium or carbamazepine during the previous 2 weeks, or fluoxetine during the previous 5 weeks. Patients were also excluded if they had received electroconvulsive therapy within the previous 8 weeks, oral or parenteral neuroleptics during the previous week, depot neuroleptics during the previous 4 weeks, an investigational drug during the previous 3 months, or were known to be intolerant to or have had a non-response to the study drugs. Patients at risk for suicide in the investigator's opinion and patients treated with oral anticoagulants.

Age: 65 years or older.


InterventionsCitalopram: 163 participants.

Mianserin: 173 participants.

Citalopram dose range: 20-40 mg/day

Mianserin dose range: 30-60 mg/day


OutcomesPrimary outcome: mean change at endpoint on MADRS.

Secondary outcomes: mean change in Clinical Global Impression-Severity (CGI-S) of Illness and Clinical Global Impression- Improvement (CGI-I) scales, Gottfries-Brane-Steen (GBS) sub-scale 3 ("emotional functions") and sub-scale 4 ("symptoms common in dementia disorders") and MMSE. In addition, a modified Well-Being Questionnaire was completed at baseline and week 12.


NotesThis study was funded by Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo clear information about sequence generation.

Quote: "Patients were randomly assigned".

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "to ensure blinding, the citalopram and mianserin tablets were identical in appearance and were taken once daily, preferably in the evening".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "two different populations were analysed: for primary efficacy analysis the efficacy population was chosen. (...) For secondary analysis, the Intention-to-treat (ITT) population was chosen. Primary and secondary efficacy variables were evaluated in both of these populations".

Selective reporting (reporting bias)High riskMADRS score and remission rate are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Khanzode 2003

MethodsTwelve-week, prospective, open-label, randomised study


ParticipantsPatients with major depression according to the DSM-IV criteria.

Exclusion criteria: patients having a score less than 14 were excluded from the study, patients with other axis I and axis II diagnoses besides major depression. Medical illnesses including endocrine, metabolic or autoimmune disorders known to affect free radical status


InterventionsCitalopram: 33 participants.

Fluoxetine: 34 participants.

Citalopram dose: 20 mg/day.

Fluoxetine dose: 20 mg/die.


OutcomesPrimary outcome: MDA and SOD concentration levels.

Secondary outcomes: change in Hamilton Depression Rating Scale (HDRS) score from baseline to week 12.


NotesIndian study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients who were suitable for drug treatment were allocated randomly".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen label study.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information provided.

Selective reporting (reporting bias)Unclear riskNo information provided.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Kyle 1998

MethodsEight-week, double-blind, parallel group, multicentre study.


ParticipantsPatients over 65 years of age diagnosed with major depression as defined by DSM-III-R criteria, with a Mini Mental State Examination (MMSE) score ≥ 24 and a score ≥ 22 on the Montgomery and Asberg Rating Scale for Depression (MADRS) at both the screening (day 7) and baseline visits (day 0).

Exclusion criteria: patients with renal or hepatic disorders, cardiovascular disorders, prostatism or urinary retention, glaucoma, epilepsy, organic mental disease, marked mental retardation, other psychiatric disorders, alcohol or drug dependence, uncontrolled diabetes or other endocrine disease, or uncontrolled hypertension, or if they required treatment with guanethidine or bethanidine. Patients receiving treatment with a psychotropic medication, those considered at suicide risk, with a recent depressive episode lasting less than 2 weeks, those with a known resistance to treatment with an SSRI or TCA, those who had taken MAO inhibitors in the last 2 weeks, and those who had taken fluoxetine in the last 5 weeks.

Age range: 65-90 in citalopram group. 65-89 in amitriptyline group.


InterventionsCitalopram: 179 participants.

Amitriptyline: 186 participants.

Citalopram dose range: 20-40 mg/day

Amitriptyline dose range: 50-100 mg/day


OutcomesPrimary outcome: mean change on MADRS score from baseline to endpoint of study.


NotesThis study was funded by Lundbeck (citalopram manufacturer).

Information about suicide attempts are not clear. Quote: "suicide attempts were observed exclusively in the amitriptyline group".


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients (...) were randomly assigned to receive citalopram or amitriptyline".

Allocation concealment (selection bias)Unclear riskNo information reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "double-blind, "double-dummy".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "all analyses were performed on data from all randomized patients who had at least one post-baseline measurement (ITT population). Patients who remained in therapy for at least 4 weeks with an average compliance of at least 50% constituted the efficacy (EFF) population".

Selective reporting (reporting bias)High riskHamilton Depression Rating Scale (HDRS) and Clinical Global Impression (CGI) scores are missing. MADRS score at baseline is missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Lalit 2004

MethodsFour-week controlled, randomised, double-blind study.


ParticipantsOutpatients, 18 to 65 years of age, with ICD-10 diagnosis of Major Depressive Episode and a minimum score of 18 on the Hamilton Rating Scale for Depression.

Patients were excluded if they had recent ongoing significant non-psychiatric medical disorder, a history of substance abuse, chronic suicidal ideation and behaviour, participated in any drug trial within 4 weeks, schizoaffective or bipolar disorder, seizure disorder, anorexia nervosa, hepatic and renal system dysfunction, therapy with lithium within the preceding month, treatment with cimetidine, warfarin or MAO inhibitors, hypersensitivity to citalopram, escitalopram and sertraline and non responders to citalopram and sertraline. Women of childbearing age not using contraceptives, pregnant women, lactating mothers, women desiring to have children were also excluded.


InterventionsCitalopram: 74 participants.

Escitalopram: 69 participants.

Sertraline: 71 participants.

Citalopram dose: 20-40 mg/day.

Escitalopram dose: 10-20 mg/day.

Sertraline dose: 100-150 mg/day.


OutcomesPrimary outcomes: change in Hamilton Rating Scale for Depression, Clinical Global Impression scores, response rate, remission rate.


NotesThis study was sponsored by Torrent pharmaceuticals.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "randomized". Likely done

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskNo clear information provided. Probably done Quote: "...double–blind, single dummy, titratable dose, parallel group, multi-centric study". And "...In order to maintain the blind, all double blind study medication was administered in alu - alu (aluminum – aluminum) strips."

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information about secondary outcome were reported. Quote: "Primary Efficacy Measures: 1) Change in HAM-D total score (The sum of all 17 items); 2) CGI –S score and CGI –I score; 3) Response rate: HAM-D score decrease by 50% from baseline; 4) Remission rate: HAM-D score below 8.

Selective reporting (reporting bias)High riskPrimary outcomes data such as HDRS total scores and CGI total scores were reported only in figures.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Langworth 2006

MethodsTwenty-four-week, double-blind, parallel group, randomised, multicentre study


ParticipantsOutpatients or day hospital clinic patients having a total score of 22 or more on the 21-item Hamilton Depression Rating Scale (HDRS-21) at screening and baseline, with major depressive disorder without psychotic features, diagnosed using DSM-IV criteria.

Age range: 16-71 years.

Exclusion criteria: medical complication or physical finding that could interfere with study activities or drug absorption, distribution, metabolism or excretion, a history of electroconvulsive therapy within the previous 6 months, hypersensitivity or a lack of response to a previous course of reboxetine or citalopram, or a positive serum pregnancy test or breast-feeding.


InterventionsCitalopram: 176 participants.

Reboxetine: 181 participants.

Citalopram: 20-40 mg/day

Reboxetine: 8-10 mg/day

Sedatives/hypnotics taken on an as-needed basis for sleep were allowed. Other psychotropic medications were not allowed.


OutcomesPrimary outcome: endpoint score on the HDRS-21.

Secondary outcomes: change from baseline in total score on Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression (CGI), Social Adaptation Self-evaluation Scale (SASS) and Sexual Function Scale (SF), response rate (reduction of at least 50% in HDRS total score from baseline), remission rate (HDRS total score of 10 or less at each post-baseline visit), time to response and time to remission.


NotesThis study was founded by Pfizer (reboxetine manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskInsufficient information to assess whether adequate sequence generation was made. Quote "patients were randomized to receive 24 weeks of treatment with reboxetine or citalopram".

Allocation concealment (selection bias)Unclear riskNo information reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo information provided.

Incomplete outcome data (attrition bias)
All outcomes
High riskQuote: "two types of analyses were performed for the primary variable (HDRS total score), namely Last Observation Carried Forward (LOCF) and Observed Cases (OC). (...) when data were analysing, it was however concluded that the LOCF analysis was less valid because there was a huge amount of missing data. Another reason for nor using the LOCF was that the treatment effect was increasing over time, which would have been ignored in an LOCF analysis. The OC was therefore finally considered as the most valid analysis for the primary efficacy variable".

Selective reporting (reporting bias)High riskNo clear data about dropout rate in each group.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Leinonen 1999

MethodsEight-week, double-blind, multicentre, randomised study.


ParticipantsPatients fulfilling the DSM-IV criteria for a major depressive episode according to the DSM-IV check-list with a total score of ≥ 22 on the Montgomery and Asberg Rating Scale for Depression (MADRS).

Exclusion criteria: patients with a history or presence of bipolar disorder, depressive disorder (not otherwise specified), schizophrenia, adjustment disorder, schizotypal or borderline personality disorder, organic mental disorder, anxiety disorders preceding depression, or presence of eating disorders (anorexia or bulimia nervosa), post-partum depression, epilepsy or a history of seizure disorder or treatment with anticonvulsant medication for epilepsy or seizures, alcohol or substance abuse during the lat 12 months, with actual risk of committing suicide defined as MADRS score 5 or 6 or assessed by investigators as being at high risk of committing suicide. Patients with a previous history or actual presence of any meaningful renal, hepatic, respiratory, cardiovascular or cerebrovascular disease or other serious, progressive physical disease, or with any clinically meaningful abnormal finding uncovered during the physical examination and/or clinically significant abnormal laboratory results at screen and still present at baseline. Non-responders to antidepressant treatment. Patients participating in any other clinical trials or treated before the start of active treatment with MAO inhibitors (2 weeks), fluoxetine (4 weeks), citalopram (current episode), electroconvulsive therapy (3 months), benzodiazepines (2 weeks), other psychotropic drugs (1 week). Women pregnant or lactating, or women who intended to become pregnant during the course of the study were not eligible for participation.


InterventionsCitalopram: 133 participants.

Mirtazapine: 137 participants.

Citalopram dose range: 20-60 mg/day (mean: 36,6 sd: 9,7)

Mirtazapine dose range: 15-60 mg/day (mean: 35,0 sd: 6,9)


OutcomesOutcomes: mean change on MADRS, Hamilton Anxiety Scale (HAM-A), Clinica Global impression (CGI), Leeds Sleep Evaluation Questionnaire (LSEQ) and Quality of Life Enjoyment and Satisfaction Questionnaire (QLESQ) score.


NotesThis study was founded by Mirtazapine manufacturer (Organon).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were allocated to treatment with either mirtazapine or citalopram, according to the centrally prepared randomization list".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "active medication was prepared as indistinguishable looking tablets and packaging was performed using a double-dummy technique".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "efficacy analyses were based on Intention-to-treat (ITT) patient sample, thus including all randomized subject who received at least one dose of study medication and had at least one post-baseline efficacy assessment on MADRS, using the Last Observation Carried forward (LOCF) method.

Selective reporting (reporting bias)Unclear riskNo information reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Lepola 2003

MethodsEight-week, double-blind, randomised, multicentre study.


ParticipantsOutpatients meeting DSM-IV criteria for Major Depressive Disorder and having a total score on Montgomery-Asberg Depression Rating Scale (MADRS) between 22 and 40.
Age range: 18-65 years.
Exclusion criteria: mania or any bipolar disorder, schizophrenia or any psychotic disorder, obsessive-compulsive disorder, eating disorder, mental retardation, any pervasive developmental disorder or cognitive disorder (according to DSM-IV criteria), MADRS score >= 5 on item 10, treatment with antipsychotics, antidepressants, hypnotics, anxiolytics, barbiturates, chloral hydrate or other 5-hydroxytryptamine receptor agonists, electroconvulsive treatment, treatment with behaviour therapy or psychotherapy.


InterventionsEscitalopram: 156 participants.

Citalopram: 161 participants.
Escitalopram dose range: 10-20 mg/day.
Citalopram dose range: 20-40 mg/day.
Benzodiazepines for insomnia were allowed.


OutcomesPrimary outcome: Change from baseline to week 8 in MADRS.
Secondary Outcomes: Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S), MADRS Individuals Items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, suicidal thoughts).


NotesThis study was funded by escitalopram manufacturer.

One fetal death in female patient treated with citalopram; one unintended pregnancy in female patient treated with escitalopram.

Remission: a score equal or less than 12 on MADRS.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Patients were randomized". Probably done.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: " there was an initial single blind placebo period, followed by randomization of eligible patients in a 1:1:1 ratio of escitalopram, citalopram and placebo treatment". The following weeks are in double-blind conditions.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Intention-to-treat (ITT) population included all randomized patients who took at least one dose of double-blind study product and who had at least one valid post-baseline MADRS assessment."

Selective reporting (reporting bias)High riskMany rating scales listed in Methods, but only a few reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Lewis 2011

MethodsTwelve-week, randomised controlled trial.


ParticipantsPatients with depression, recruited in primary care, aged 18-74 years who had already agreed with their general practitioner that antidepressant should be prescribed.

Patients who had taken antidepressant medication within the 2-weeks prior to the baseline assessment and those who could not complete self-administered scales were excluded. General practitioner also excluded those with medical contraindications, psychosis, bipolar affective disorder, major substance or alcohol misuse and others whose participation was deemed inappropriate.


InterventionsCitalopram: 298 participants.

Reboxetine: 303 participants.

Citalopram dose: 20 mg/day.

Reboxetine dose: 8 mg/day.


OutcomesPrimary outcome: total Beck depression Inventory Score (BDI) at 6-weeks.

Secondary outcomes: remission rates (defined as BDI score < 10) at 6-weeks, Short Form Health Survey mental and physical sub-scale scores and Hospital Anxiety and Depression Scale total scores.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was conducted using a computer-generated code, administered centrally and communicated by telephone and thereby concealed in advance from the researcher. Allocation was stratified by severity of symptoms and by centre, using variable block sized to maximise concealment".

Allocation concealment (selection bias)Low riskQuote: "(Randomization was) concealed in advance from the researcher. Allocation was stratified by severity of symptoms and by centre, using variable block sized to maximise concealment".

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo data reported

Incomplete outcome data (attrition bias)
All outcomes
High riskHigh attrition rate and unbalance between treatment groups (about 20% of lost to follow up in the citalopram group and about 30% in the reboxetine group)

Selective reporting (reporting bias)Low riskPrimary outcome data were reported.

Other biasLow riskSponsorship bias can be ruled out.

Lu 10-171, 83-01

MethodsSix-week, randomised, double-blind study.


ParticipantsIn-and outpatients of either sex, 18-65 years old, who had given their informed consent to participate in the study, and who were suffering from a major depressive episode (DSM-III classification) of a severity corresponding to a total score of at least 18 points on the HDRS-17 items.

Exclusion criteria: concurrent somatic disease (particularly severe liver, heart or kidney disease); pregnancy or absence of use of an effective contraceptive method; a history of epilepsy, glaucoma, urinary retention, alcoholism, pyloric stenosis or symptomatic prostatic hypertrophy, marked mental subnormality, need of ECT or administration of ECT during the previous month, treatment with TCA in adequate dosage (100 mg/day of amitriptyline or equivalent) during the last month or with a MAO-I during the last 2 weeks prior to entry into the study.


InterventionsCitalopram: 23 participants.

Citalopram dose range: 20-60 mg/day.

Imipramine: 22 participants.

Imipramine dose range: 50-150 mg/day.


OutcomesOutcomes: Change from baseline to week 6 in HDRS-17 items, Leeds self rating scale.


NotesThis study was funded by Lundbeck.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "the randomization was made in block of 4 according to a code prepared by the Biostatistical Department of Lundbeck".

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "double blind study".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information reported.

Selective reporting (reporting bias)Unclear riskNo information reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Lu 10-171,79-01

MethodsEight-week, double-blind, randomised study.


ParticipantsHospitalised depressed patients who needed antidepressant medication.

Age range: 18-65 years.

Exclusion criteria: patients with severe somatic disorders (particularly in heart, liver and kidney), pregnant patients and patients who did not wish to participate after having been informed of the trial.


InterventionsCitalopram: 21 participants.

Citalopram dose range: 40-60 mg/day.
Nortriptyline: 22 participants.

Nortriptyline dose range: 50-150 mg/day.


OutcomesOutcomes: change in the severity of depression assessed using the HDRS and CGI scores.


NotesThis study was funded by Lundbeck.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients fulfilling the inclusion criteria were allocated randomly".

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "in order to ensure blindness, the nortriptyline tablets were supplemented with placebo tablets up to a total of 4 tablets. The initial dose of nortriptyline was estimated for all patients, and in accordance with the randomization list the drugs were packed by the hospital laboratory in doses boxes containing citalopram only or nortriptyline plus any necessary placebo tablets".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information reported.

Selective reporting (reporting bias)Unclear riskNo information reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Matreja 2007

MethodsSix-week, open-label, prospective, randomised study.


ParticipantsPatients suffering from Major Depressive Disorder as per DSM-IV criteria were enrolled in the study, with Hamilton Depression Rating Scale (HDRS) score >18.

Age range: 18-75 years.


InterventionsCitalopram: 50 participants.

Sertraline: 50 participants.

Citalopram dose range: 20-60 mg/day (mean dose: 33 sd: 13).

Sertraline dose range: 50-150 mg/day (mean dose 96 sd: 35).


OutcomesOutcomes: change in the severity of depression assessed using the HDRS, Montgomery and Asberg Rating Scale for Depression (MADRS) and Amritstar Depressive Inventory (ADI) scores.


NotesNo information provided about study sponsorship.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "a total of 100 patients were randomized into two groups as per random number table". Probably done.

Allocation concealment (selection bias)Unclear riskNo information about allocation concealment.

Blinding (performance bias and detection bias)
All outcomes
High riskOpen-label study.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "the primary statistical analysis was Intention-to-treat (ITT) for all safety and efficacy variables with the Last Observation Carried Forward (LOCF) for those patients who had at least 2 weeks data".

Selective reporting (reporting bias)High riskAlso data about individual side-effects are missing.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Moeller 2003

MethodsFour-week, prospective, randomised study.


ParticipantsIn-patients fulfilling DSM-IV criteria for unipolar depression.

Exclusion criteria: patients who were not physically healthy, needed further medication, had a history of endocrine disorders, were pregnant or were suffering from alcohol or drug abuse.

Age range: 19-67 in citalopram group; 16-64 in reboxetine group.


InterventionsCitalopram: 19 participants.

Reboxetine: 17 participants.

Citalopram fixed dose: 40 mg/day.

Reboxetine fixed dose: 8 mg/day.

Only diazepam and zaleplon were allowed as additional medications.


OutcomesPrimary outcome: basal prolactin levels from baseline to endpoint.

Secondary outcomes: mean change on Hamilton Depression Rating Scale (HDRS) and Montgomery and Asberg Rating Scale for Depression (MADRS) scores from baseline to endpoint.


NotesThree days before tests started, patients were treated exclusively with diazepam (for agitation) and zaleplon (for insomnia) in order to wash out previous antidepressant medication.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "Patients were assigned randomly".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "patients were not blinded about medication".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information provided

Selective reporting (reporting bias)Unclear riskNo information provided

Other biasUnclear riskSponsorship bias cannot be ruled out.

Moore 2005

MethodsEight-week, double-blind, prospective, multicentre, randomised study.


ParticipantsOutpatients meeting DSM-IV criteria for Major Depressive Disorder (MDD) and having a Montgomery-Asberg Depression Rating Scale (MADRS) total score at baseline of at least 30.

Age range: 18-65 years.

Exclusion criteria: patients meeting criteria for primary diagnoses of any axis I disorder other than MDD, or those with a history of mania, bipolar disorder, schizophrenia or other psychotic disorder, obsessive- compulsive disorder, cognitive disorder including mental retardation or personality disorder. Patients who met DSM criteria for substance abuse or dependence within the past 12 months, or who used a depot antipsychotic within 6 months before study inclusion, or any antipsychotic, anxiolytic or anticonvulsant medication within 2 weeks before the first administration of study medication.


InterventionsEscitalopram: 138 participants.

Citalopram: 142 participants.

Escitalopram fixed dose: 20 mg/day.

Citalopram fixed dose: 40 mg/day.


OutcomesPrimary outcome: mean change from baseline to endpoint on the MADRS.

Change from baseline to last assessment score in the Clinical Global Impression-Severity Scale (CGI-S).


NotesThis study was funding by H. Lundbeck A/S.

One suicide completed in citalopram group after 12 days of treatment.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients meeting eligibility criteria were randomly assigned (...) with equal block randomization at baseline".

Allocation concealment (selection bias)Unclear riskInsufficient information.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "double-blind" but author not give other information.

Incomplete outcome data (attrition bias)
All outcomes
Low riskEfficacy analysis on Intention-to-treat (ITT) population (all patients who took at least one dose of study medication and who had at least one valid post-baseline MADRS assessment).

Selective reporting (reporting bias)High riskMany rating scales listed in Methods, but only a few reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Navarro 2001

MethodsTwelve-week, randomised, single-blind study.


ParticipantsIn- and out-patients with unipolar major depression fulfilling the DSM-IV criteria for a current major depressive episode, with or without endogenous or psychotic features. Only elderly patients with late-onset depression were included (depression late-onset had to have begun after the age of 50).

Age: 60 years or over.

Exclusion criteria: patients with significant abnormal biological findings on electrocardiographic or laboratory examination, those with focal neurological findings or systemic neurological disorder (e.g. seizure disorders, stroke, Parkinson's disease) and those with uncontrolled medical illness at the time of recruitment. Patients with a manic or hypomanic episode, any history of psychosis, current substance dependence and electroconvulsive therapy within 6 months of recruitment.


InterventionsCitalopram: 29 participants.

Nortriptyline: 29 participants.

Citalopram dose range: 30-40 mg/day (mean dose: 33.45; SD 4.84)

Nortriptyline dose range: 50-100 mg/day (mean dose: 61.11; SD 17.45)

Lorazepam up to 4 mg/day was allowed for management of anxiety or insomnia.


OutcomesPrimary outcome: mean change in Hamilton Depression Rating Scale (HDRS) score from baseline to endpoint.


NotesSix patients with psychotic symptoms (two in nortriptyline group and four in citalopram group) received haloperidol up to 4 mg/day during the first 4 weeks.

Eligible patients underwent a 2-week washout period. Rapid wash-out responders (HDRS decreased by 25% or more) were excluded from the study.

This study was partially supported by a research grant from the Investicacions Biomediques August Pi i Sunyer Institut (IDIBAPS) to Victor Navarro and by FIS grant 99/0171.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "subjects were randomly divided into two subgroups".

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "single-blind", but author not give other information.

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "statistical analyses of safety data were conducted on all patients randomized to treatment who took at last one dose of study medication. Efficacy analyses included all modified intent to treat patients: that is all patients randomized to treatment who took their assigned medication for 4 weeks or more".

Selective reporting (reporting bias)Unclear riskNo reliable data provided.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Ou 2010

MethodsSix-week, randomised, parallel group, controlled study.


ParticipantsIn- and out-patients were recruited if they met the following criteria: age 18-65 years, diagnosis of Major depressive Disorder (MDD) as defined as Axis I of the DSM-IV, total score of the Hamilton Depression Rating Scale 17 Item (HDRS-17) > or = 17, in the opinion of the treating psychiatrist, potential benefit from treatment with one or the other study drugs.

Exclusion criteria: patients were excluded if they met DSM-IV Axis I criteria for mania or any bipolar disorder, schizophrenia or any psychotic disorder or displayed any psychotic features, obsessive-compulsive disorder, mental retardation or any pervasive developmental disorder, eating disorder (anorexia nervosa or bulimia nervosa), dementia, or alcohol or drug abuse within the previous 12 months. further exclusion criteria were a history of severe drug allergy or hypersensitivity, other serious illness or sequela of serious illness, citalopram or escitalopram treatment within 60 days prior to inclusion, and/or inability to comply with the protocol in the investigator's opinion. Patients were also excluded if they serious tended to suicide. Patients who had joined any other clinical trial or who received oral antipsychotic drugs, monoamine oxidase inhibitors, or electroconvulsive therapy within 4 weeks prior to initiation of the study were also excluded. Women who were pregnant or breast feeding were also excluded.


InterventionsCitalopram: 120 participants.

Escitalopram: 120 participants.

Citalopram dose range: 20 mg/day.

Escitalopram dose range: 10 mg/day.


OutcomesPrimary outcome: change in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint.

Secondary outcome: patients who responded to treatment, patients who remitted.


NotesEligible patients underwent a 1- to 7-day washout period. This study was funded by the National institutes of Pharmaceutical Research and Development Co., Ltd., and all drugs were provided by the company. The sponsor’s only role was in the design and monitoring. The company had no further role in data collection, analysis, and interpretation or writing of this paper, or in the decision to submit the paper for publication.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were randomized (without restriction or stratification) through a computer-generated table to one of the two treatments in blocks of four to ensure approximately equal numbers in the two treatment groups".

Allocation concealment (selection bias)Low riskQuote: "to ensure concealment of the randomization, which was conducted independently of the investigators by a research pharmacist at a separate facility, medication was provided in coded packages".

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "medication was provided in coded packages containing the drugs, which were identical in appearance, taste and odor".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "Efficacy analysis was conducted in the Intention-to-treat population, which included all patients who received at least one dose of medication and had data available from at least one valid post-baseline efficacy assessment".

Selective reporting (reporting bias)Unclear riskNo reliable data provided.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Rosenberg 1994

MethodsTwenty-two-week, multicentre study. The primary treatment period was 6 weeks. However, patients who in the opinion of the investigator would benefit from further treatment could continue treatment under double-blind conditions for a further 16 weeks, i.e. for a total of 22 weeks.


ParticipantsDepressed patients of either sex, who were assessed as being in need of antidepressant treatment and who had a total score of 14 or more on the Hamilton Depression Rating Scale (HDRS)

Age range: 18-65 years.

Exclusion criteria: pregnancy, failure to use an acceptable contraceptive method, known alcohol or drug abuse within the past year, psychosis, serious somatic disease, treatment with MAO inhibitors within the last 2 weeks or with other antidepressants within the last week before inclusion and hypersensitivity to test drugs. Patients who required psychiatric in-patient treatment were also excluded.


InterventionsCitalopram 10-30 mg/day: 187 participants.

Citalopram 20-60 mg/day: 193 participants.

Imipramine 50-150 mg/day: 92 participants.

Benzodiazepines or sedatives antihistamines could be prescribed for sleep disturbance, but other psychotropic drugs were not allowed.


OutcomesPrimary outcome: mean change in HDRS score from baseline to endpoint.

Secondary outcomes: mean change in Clinical Global Impression (CGI) and Visual Analogue Scale (VAS) score, HDRS factors as depression, sleep disturbances, anxiety/somatization, retardation.


NotesThis study was funded by Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Patients were randomly allocated to one or two dose levels of citalopram or imipramine treatment. In each block of five patients one patient received imipramine and two pairs of patients each received one of the two citalopram dose". Randomization ratio 1:2:2.

Allocation concealment (selection bias)Unclear riskNo data provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "This study was a double blind comparison (...) tablets of identical appearance were used".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: "All patients receiving at least one tablet constituted the Intention-to-treat (ITT) population. Patients who met the inclusion and exclusion criteria, had a compliance of 50% or higher and who completed at least 14 days of treatment constituted the Efficacy Population (EFF).

Selective reporting (reporting bias)Unclear riskNo clear information reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

SCT-MD-02

MethodsEight-week, double-blind, randomised, multicentre study.


ParticipantsOutpatients meeting DSM-IV criteria for Major Depressive Disorder (MDD) and having a minimum score of 22 on Montgomery-Asberg Depression Rating Scale (MADRS) and a minimum score of 2 on Item 1 of Hamilton Depression Rating Scale (HDRS).
Age range: 18-80 years.


InterventionsEscitalopram: 129 participants.
Citalopram: 128 participants.
Escitalopram dose range: 10-20 mg/day.
Citalopram dose range: 20-40 mg/day.


OutcomesPrimary Outcome: Change from baseline to week 8 in MADRS.
Secondary outcomes: HDRS, HDRS Depressed Mood Item, Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity (CGI-S).


NotesThis study was funded by escitalopram manufacturer.

Only unpublished data.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "randomized". Probably done.

Allocation concealment (selection bias)Unclear riskNo clear information reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "double-blind".

Incomplete outcome data (attrition bias)
All outcomes
Low riskQuote: Intention-to-treat (ITT) analysis ("all patients with at least one post-baseline assessment of MADRS").

Selective reporting (reporting bias)Unclear riskNo clear information reported.

Other biasUnclear riskNo reliable information reported.

Shaw 1986

MethodsSix-week, double-blind, randomised study.


ParticipantsIn- and out-patients who met the DSM-III criteria for Major Depressive illness, scored 18 or more on the 17-item Hamilton Depression Rating Scale Scale (HDRS). All participants entered into the trial within 36 hours of admission (48 hours at week end).

Age range: 18-70 years.


InterventionsCitalopram: 29 participants.

Amitriptyline: 30 participants.

Citalopram dose range: 30-60 mg/day.

Amitriptyline dose range: 112.5-225 mg/day.


OutcomesOutcomes: mean change on HDRS and Montgomery-Asberg Depression Rating Scale (MADRS), Newcastle Scale, Leeds Self-rating Depression Scale.


NotesThe study was funded by Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "the trial was randomized in blocks of four".

Allocation concealment (selection bias)Unclear riskNo reliable information reported.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote: "double blind".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo reliable information reported.

Selective reporting (reporting bias)Unclear riskNo reliable information reported.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Stahl 2000

MethodsTwenty-four-week, eight centres, double-blind randomised trial.


ParticipantsPatients who satisfied DSM-IV criteria for Major Depressive Disorder (MDD) with a minimum 2 months duration of illness, with a score of at least 22 on the Hamilton Depression Rating Scale (HDRS) , a minimum score of 2 on Depressed Mood Item and a minimum score of 8 on Raskin Depression Scale together with a lower score on the Covi Anxiety Scale.
Age range: 18-60 years old.

Exclusion criteria: pregnancy, inadequate contraception, another DSM-IV Axis I diagnosis, use of other psychotropic medication, increased risk of suicide, treatment resistance, history of sertraline intolerance or SSRI hypersensitivity reactions, history of alcohol or substance abuse.


InterventionsSertraline: 108 participants.
Citalopram: 107 participants.
Placebo: 108 participants.
Sertraline dose range: 50-150 mg/day.
Citalopram dose range: 20-60 mg/day.
Chloral Hydrate was permitted.


Outcomes21-HDRS, MADRS, Clinical Global Impression-Severity (CGI-S) andClinical Global Impression-Improvement (CGI-I), Hamilton Anxiety Scale (HAM-A), Symptom Checklist-56 (SCL-56), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).


NotesThis study was funded by Lundbeck (citalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote "randomized". Probably done, as a similar trial by these investigators included the same phrase and used a proper method of allocation.

Allocation concealment (selection bias)Unclear riskInsufficient information.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskQuote "double-blind" but authors did not give other information.

Incomplete outcome data (attrition bias)
All outcomes
High riskMissing data and standard deviations.

Selective reporting (reporting bias)Unclear riskThe study protocol is not available.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Timmerman 1993

MethodsSix-week, double-blind, randomised, parallel group, multicentre study.


ParticipantsCooperative out-patients of either sex with a reasonable knowledge of the Dutch language, who met the DSM-III-R criteria for "Major Depression, single episode", "Major Depression, recurrent", "Bipolar Disorder, depressed", with a score of a least 16 on the 17 items Hamilton Depression Rating Scale (HDRS).

Age range: 18-70 years.

Exclusion criteria: patients who had been treated with MAO inhibitors or fluoxetine within the last 3 weeks or with other psychotropic drugs within the last week, with the exception of benzodiazepines. Patients with another primary psychiatric diagnosis than the above mentioned, or with a history of epilepsy, alcohol and/or drug abuse, pregnant or lactating women and women with childbearing potential failing to use standard birth control methods as well as patients with renal, hepatic, cardiovascular, neurological or somatic disorders, and/or significant abnormal laboratory findings.


InterventionsCitalopram: 108 participants.

Fluvoxamine: 109 participants.

Citalopram dose range: 20-40 mg/day

Fluvoxamine dose range: 100-200 mg/day


OutcomesPrimary outcome: mean change on HDRS score from baseline to endpoint.

Secondary outcomes: change in Clinical Global Impression-Severity (CGI-S) score, in the Zung Self-rating Scale for depression score.


NotesThe study was funded by Lundbeck (citalopram manufacturer).

One suicide completed in citalopram group, one fatal myocardial infarction in citalopram group, two suicide attempted in fluvoxamine group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were randomly assigned".

Allocation concealment (selection bias)Unclear riskNo reliable information reported.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "patients were randomly assigned to double-blind treatment".

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskQuote: "the Intention-to-treat (ITT) population included all patients who had been allocated a randomization number to entry of double-blind treatment".

Selective reporting (reporting bias)Unclear riskThe study protocol is not available.

Other biasUnclear riskSponsorship bias cannot be ruled out.

Yevtushenko 2007

MethodsSix-week, prospective, randomised, double-blind, active-controlled trial was conducted at eight psychiatric outpatient clinics across the Federation of Russia.


ParticipantsOutpatients, aged 25 (this minimum age limit was a requirement of one of the ethics committees) to 45 years, with a diagnosis of Major Depressive Disorder (MDD), as defined in the DSM-IV criteria and a total score more than or equal to 25 on Montgomery-Asberg Depression Rating Scale (MADRS). Patients were not eligible if they met DSM-IV criteria for mania or any bipolar disorder, schizophrenia, or any psychotic disorder, or displayed any psychotic features, obsessive-compulsive disorder, mental retardation or any pervasive developmental disorder, eating disorder (anorexia nervosa or bulimia nervosa), dementia, or alcohol or drug abuse within the previous12 months, a history of severe drug allergy or hypersensitivity, other serious illness or sequela of serious illness, citalopram or escitalopram treatment within 60 days prior to inclusion. Patients were also excluded if they had received an oral antipsychotic drug or monoamine oxidase inhibitor within 2 weeks prior to inclusion; a depot antipsychotic preparation within 6 months prior to inclusion; an SSRI (except fluoxetine), a serotonin-noradrenaline reuptake inhibitor, or a TCA within 1 week prior to inclusion; or fluoxetine within 5 weeks before inclusion; an antiparkinsonian compound, barbiturate, chloral hydrate, lithium, anticonvulsant, or hypnotic and anxiolytic (except for benzodiazepines used for insomnia at a stable dose for the previous 6 months or used episodically at a lower recommended dose). Women who were pregnant or breast feeding were also excluded from the study.


InterventionsUsing equal (˜110 patients per group) block randomisation, patients were assigned to receive a once-daily fixed dose of escitalopram 10 mg (109 participants), citalopram10 mg (111 participants), or citalopram 20 mg (110 participants) for 6 weeks.


OutcomesThe primary efficacy measure was the change in the MADRS total score from baseline to end of study. Secondary efficacy measures were changes from baseline in MADRS total score in a subgroup of severely depressed patients (MADRS total score more than or equal to 35), MADRS core depression subscale score (in the overall population and severely depressed subgroup), Clinical Global impression- Severity (CGI-S), and Clinical Global impression- Improvement (CGI-I). In addition, the proportions of patients classified a priori as responders (decrease in MADRS total score by at least 50% of the baseline value) or remitters (primary definition, MADRS total score less than or equal to 12; secondary definition, less than or equal to 10) were analysed.


NotesThe present study was part of the S-citalopram development program for approval in some European Countries through a bridging procedure using results from studies of the racemate, citalopram. Care and medication were free of charge for the patients enrolled in the trial. This study was specifically designed a priori as a superiority study. The sample size was calculated using Singer’s method. The largest between-group difference was estimated at 5 points, with an SD of 12. Given this assumption, and with an a level of 5% (2-tailed) and a b level of 20%, it was calculated that 100 patients per arm would be needed to achieve sufficient power. Assuming a 10% withdrawal rate, 10 additional patients per arm were included in the design to ensure sufficient power, giving 110 patients per arm (330 patients in total). This research was sponsored by OOO ARBACOM (Moscow, Federation of Russia) (it's unclear the relationship with the escitalopram manufacturer).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "...Eight equal block randomizations were generated, 1 per center." Probably done.

Allocation concealment (selection bias)Unclear riskNo information provided.

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "To maintain blinding, all study medication was provided in capsules (tablets were encapsulated in a lactose powder) that were identical in appearance, taste, and odor.Investigators and patients were blinded to treatment."

Incomplete outcome data (attrition bias)
All outcomes
Low riskLast Observation Carried Forward (LOCF) method of replacing missing values.

Selective reporting (reporting bias)Unclear riskThe study protocol is not available.

Other biasUnclear riskSponsorship bias cannot be ruled out.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Adli 2008Wrong design (non-randomised).

Altamura 2008Wrong intervention.

Altamura 2008bWrong intervention.

Amiaz 2008Wrong diagnosis.

Amsterdam 2006Wrong design (non-randomised).

Amsterdam 2008Medical/psychiatric comorbidity.

Anderer 2002Wrong comparison.

Andersen 1993Post-stroke depression.

Angermann 2007Depressed heart failure patients.

Anon 1995Not compared with other antidepressive agents.

Anonymous 2011Wrong design (not randomised).

Azorin 2004This study pooled from three different clinical trials.

Baldwin 2006Duplicate publication.

Barone 2011Medical/psychiatric comorbidity.

Bauer 2010Wrong comparison.

Baumann 1998aNot compared with other antidepressive agents.

Baumann 1998bNot compared with other antidepressive agents.

Benkelfat 1987Only two patients randomised to citalopram.

Berney 2008Not compared with other antidepressive agents.

Bersani 1997Not compared with other antidepressive agents.

Beving 1985Non-randomised study.

Bhagwagar 2004Patients with a previous history of depression.

Bigos 2008Wrong population.

Bijl 2004Wrong comparison (Escitalopram for depression).

Bjerkenstedt 1985Not compared with other antidepressive agents.

Blier 2006Patients randomised to various treatment strategies, including augmentation strategies and psychotherapy (STAR*D study).

Bouchard 1997Wrong formulation of intervention (e.v.).

Boulenger 2010Wrong comparison.

Bowden 1998Wrong diagnosis (bipolar patients were included).

Brown 2004Not compared with other antidepressive agents.

Bryan 2007Association of diabetes mellitus with response to depression treatment.

Bun'kova KMWrong comparison.

Carman 2002Patients with major depression or bipolar disorder.

Chakravarti 2002Wrong design.

Chan 2009Medical comorbidity.

Chen 2005Post-stroke depression.

Conte 1997Not compared with other antidepressive agents.

Cooper-Kazaz 2011Double publication of Stahl 2000.

Court 2010Wrong diagnosis.

Culang 2009Wrong comparison.

Daly 2011Wrong design (not randomised).

Davis 2006Patients randomizsd to various treatment strategies, including augmentation strategies and psychotherapy (STAR*D study).

Davis 2010Wrong comparison.

Davis 2010bWrong design (non-randomised).

Deakin 2002Not compared with other antidepressive agents.

DeBattista 2011Wrong comparison.

Dell'Agnello 2001Medical/psychiatric comorbidity.

Dell'Osso 2008Wrong comparison.

Deng 2006Wrong comparison (citalopram combined with quetiapine).

Denko 2007Patients randomized to various treatment strategies, including augmentation strategies and psychotherapy (STAR*D study).

Devos 2008Medical/psychiatric comorbidity.

Di Simplicio 2010Wrong design (non-randomised).

Diniz 2010Wrong diagnosis.

Doggrell 2006Wrong diagnosis (resistant depression).

Domelas 2007Patients with coronary artery disease.

Doree 2007Quetiapine augmentation for treatment resistant depression.

Dougherty 2009Wrong diagnosis.

Dozois 2009Wrong comparison.

Dunbar 2010Wrong comparison.

Eriksson 1996Wrong diagnosis.

Eyding 2010systematic review and meta-analysis (citalopram studies already included in the present review).

Fava 2006Patients randomised to various treatment strategies, including augmentation strategies and psychotherapy (STAR*D study).

Feighner 1997Not compared with other antidepressive agents.

Feighner 1997bWrong comparison.

Feighner 1999Not compared with other antidepressive agents.

Fernandez 2005Double reference.

Fernandez 2009Medical/psychiatric comorbidity.

Flicker 1998Patients with or without dementia.

Ford 2010Wrong comparison.

Fraguas 2009Medical/psychiatric comorbidity.

Frank 2004Wrong design.

Garriock 2010Wrong design (non-randomised).

Gilbert 2008Wrong design (non-randomised).

Gilmer 2008Wrong design (non-randomised).

Glod 2004Patients are adolescents.

Goder 2011Wrong design (not randomised).

Gommol 2010Wrong comparison.

Gonsai 2000Wrong population.

Gorman 2002aWrong design.

Gorwood 2007Escitalopram for preventing relapse.

Guelfi 1998Not compared with other antidepressive agents.

Hannestad 2011Wrong comparison.

Harrington 2002Not compared with other antidepressive agents.

Hegerl 2005Non randomised design.

Hellerstein 2010Wrong comparison.

Hemels 2004Economic evaluation.

Herrera-Guzman 2009Wrong comparison.

Hflich 2011Wrong design.

Hindmarch 2000Discontinuation treatment.

Hochstrasser 2001Maintenance therapy.

Holtzheimer 2008Wrong comparison.

Howland 2011Wrong design.

Huezo-Diaz 2009Wrong comparison.

Johnson 2002Wrong design.

Judge 2000Non randomised design.

Kapitany 1999Not compared with other antidepressive agents.

Kasckow 2010Wrong diagnosis.

Kasper 2009Wrong comparison.

Ketter 2006Wrong diagnosis.

Khazaie 2006Not randomised design.

Khazaie 2011Medical comorbidity.

Kiosses 2010Wrong intervention.

Klysner 2000Not compared with other antidepressive agents.

Kornstein 2006Escitalopram for relapse prevention.

Kovacs 1998Not compared with other antidepressive agents.

Kraus 2008Medical/psychiatric comorbidity.

Kroenke 2009Medical/psychiatric comorbidity.

Kuhn 2003Medical comorbidity.

Kupfer 2000Double reference.

Lakey 2008Non major depression.

Lam 2008Wrong comparison.

Lavretsky 2010Wrong comparison.

Leuchter 2009Wrong comparison.

Li WQ 2006Vascular depression.

Lindsley 2010Wrong comparison.

Linnet 1996Wrong design.

Liu 2006bMedical/psychiatric comorbidity.

Liu 2006cMedical/psychiatric comorbidity.

Llacer 2007Depressed patients with anxiety and insomnia.

Lydiatt 2006Wrong population.

Maas 2010Wrong comparison.

Maksinczyk 1997Bipolar depression.

Malik 2002Treatment for depression as risk factor for ischemic heart disease.

Mannu 2009Wrong comparison.

Martinez 2012Wrong design.

Martini 2007Not compared with other antidepressive agents.

Martiny 2004Not compared with other antidepressive agents.

Martire 2008Wrong population.

McCabe 2010Wrong population (healthy people).

Mcgrath 2008Wrong design (non-randomised).

Mendels 1990Not compared with other antidepressive agents.

Meyer 2001Not randomised design.

Miao 2004Post-stroke depression.

Minelli 2010Wrong comparison.

Miskowiak 2009Wrong comparison.

Moltzen 2005Wrong comparison.

Morasco 2010Medical/psychiatric comorbidity.

Moretti 2002Depression and Alzheimer’s disease.

Muhonen 2008Medical/psychiatric comorbidity.

NCT00048815Wrong diagnosis.

Nierenberg 2004Minor depression.

Nowak 2003Zinc supplementation on antidepressant therapy.

Nunez 1999Not compared with other antidepressive agents.

Nurnberg 2008Wrong comparison.

Nyth 1990Not compared with other antidepressive agents.

Oberpichler-Schwenk 2000Wrong design.

Pae 2011Wrong comparison.

Palmer 2002Not compared with other antidepressive agents.

Papakostas 2000Not compared with other antidepressive agents.

Parvin 2011Wrong intervention.

Perlis 2009Wrong comparison.

Petersen 1998Double reference.

Pogosova 2004Not compared with other antidepressants.

Portella 2010Wrong comparison.

Prasko 2003Cognitive behavioural therapy (short or long term) combined with pharmacotherapy.

Quante 2010Wrong comparison.

Raisi 2007Combination of citalopram and nortriptyline.

Rampello 2004Wrong population.

Rampello 2004aCitalopram alone or in combination with amitriptyline; patients with different diagnosis in comorbidity.

Rampello 2004bPost-stroke depression.

Rampello 2006Treatment for panic attack.

Rapaport 2010Wrong comparison.

Rapaport 2011Wrong diagnosis.

Rapoport 2010Wrong comparison.

Raskin 2011Wrong population.

Rasmussen 1992Not compared with other antidepressive agents.

Riva 2006Evaluation of integrated pharmacologic and psychotherapeutic treatment.

Robinson 2008Post-stroke depression.

Robinson 2009Wrong population.

Rocca 2005Non major depression.

Roose 2004Not compared with other antidepressants.

Rosenthal 2002Wrong comparison.

Rush 2008Wrong comparison.

Salloway 2002Not compared with other antidepressants.

Schaefer 2008Medical/psychiatric comorbidity.

Schfer 2010Medical/psychiatric comorbidity.

Schmitt 2006Escitalopram as continuation treatment of intravenous citalopram.

Segal 2010Wrong population.

Serfaty 2010Wrong comparison.

Sharp 2010Wrong comparison.

Smith 2011Wrong intervention.

Sneed 2007Wrong comparison.

Soares 2006Peri and post menopausal women.

Soares 2010Wrong comparison.

Souery 2010Wrong population.

Stein 2001Wrong diagnosis.

Stein 2005Psychotherapy plus pharmacotherapy for drug users.

Sun 2004Refractory depression.

Swartz 2008Wrong comparison.

Talati 2007Patients randomised to various treatment strategies, including augmentation strategies and psychotherapy (STAR*D study).

Targacept 2008Wrong design and wrong intervention.

Thase 2010Pooled-analysis (citalopram studies already included in the present review)

Thase 2011Wrong design.

Thorell 1999Seasonal affective disorder.

Uher 2010Wrong comparison.

Van Bemmel 1993Not compared with other antidepressants.

Voirol 1999Wrong design (non-randomised).

Wade 2000Not compared with other antidepressants.

Wade 2006Wrong intervention.

Wagner 2002Patients are children and adolescents.

Wang 2005Diagnosis is “depression induced by Alzheimer”.

Warden 2009Wrong intervention.

Wermuth 1998Parkinson’s disease; not compared with other antidepressants.

Wise 2011Wrong population.

Wisniewski 2009Wrong intervention.

Wu 2008Wrong design (non-randomised).

Yang 2005Refractory depression.

Yang 2010Wrong intervention.

Zhao 2005Post stroke depression.

Zimbroff 2004Citalopram for non responders depressive-patients.

Zisook 2007Patients with schizophrenia.

Zisook 2010Wrong diagnosis.

Zou 2005Citalopram combined with psychological morning exercise.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Ahlfors 1988

MethodsFour-week, randomised, double-blind, multicentre study

ParticipantsPatients with depression, aged from 18 to 70 years and referred to a psychiatric hospital for a depression requiring treatment.

InterventionsCitalopram: 37 participants.

Mianserin: 34 participants.

Citalopram dose-range: 20-60 mg/day.

Mianserin dose-range: 60-90 mg/day.

OutcomesChange in Montgomery and Asberg Depression Rating Scale (MADRS) from baseline to endpoint.

NotesTwo patients in Mianserin group died (the reason could not be ascribed to the test treatment).

Akimova 2010

MethodsDouble-blind, randomised, longitudinal PET study using radioligand [11C]DASB

Participants18 patients

Interventions10 mg/d escitalopram or 20 mg/d citalopram, i.e. equal doses of the enantiomer S-Citalopram

OutcomesSerotonin transporter availability in the unmedicated state and SERT occupancy after a single-dose and later after the first 3 weeks of treatment with SSRIs. The Hamilton Depression Rating scale (HAM-D, 17 items) was assessed at the screening visit and before each PET scan.

NotesRadioligand [11C]DASB is a new, highly selective PET radiotracer that shows a high affinity for serotonin transporter

Akimova 2011

MethodsDouble-blind, longitudinal study.

ParticipantsPatients with MDD.

InterventionsCitalopram: 20mg/day.

Escitalpram: 10mg/day.

OutcomesAlterations in different brain regions assessed with PET scans using the radioligand [11C]DASB.

Notes

Aydemir 2011

MethodsIn the treatment of major depressive disorder, in addition to the remission of symptoms, improvement in functionality and subjective quality of life of the patients is desirable. In this study, we aimed to evaluate and compare the changes in quality of life measures in citalopram- versus escitalopram-treated major depressive disorder patients, and to compare the scores of the patients who achieved remission at the end of treatment with standard scores of the Turkish population.

Participants74 outpatients with major depressive disorder

InterventionsCitalopram was started at a dose of 20 mg/day, and escitalopram was started at a dose of 10 mg/day. At the end of the 6th week, the mean dose for the citalopram treated patients was 24.6 mg/day and for the escitalopram treated patients it was 11.8 mg/day.

OutcomesTreatment response was accepted as a 50% decrease in the index assessment and remission was accepted as HAM-D<=7

Notes

Du 2004

MethodsSix-week, (likely) randomised study.

ParticipantsPatients with depression according to CCM-II criteria.

InterventionsCitalopram: 32 participants.

Amitriptyline: 32 participants.

Citalopram dose-range: 20-40 mg/day.

Amitriptyline dose-range: 75-250 mg/day.

OutcomesChange in Hamilton Depression rating scale (HDRS) from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Fu 2006

MethodsSix-week, randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 34 participants.

Amitriptyline: 34 participants.

Citalopram dose-range: 20-60 mg/day (mean dose: 28.82 SD: 10.67).

Amitriptyline dose-range: 50-175 mg/day (mean dose: 113.24 SD: 29.02).

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Galecki 2004

MethodsSix- week study.

Participants89 elderly patients with a serious depressive episode were involved in the study.

InterventionsCitalopram: 44 participants.

Venlafaxine: 45 participants.

OutcomesThe clinical state of patients was assessed by Hamilton Depression rating Scale (HDRS), a geriatric depressive scale (GDS) and a clinical general impression scale (CGI). Cognitive functions were examined by Mini-Mental scale.

NotesWaiting for translation from Polish to English (only abstract available in English).

Gao 2005

MethodsSix-week, (likely) randomised study.

ParticipantsIn and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Amitriptyline: 30 participants.

Citalopram dose-rage: 20-50 mg/day.

Amitriptyline dose-range: 100-200 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Gong 2005

MethodsEight-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 49 participants.

Mirtazapine: 49 participants.

Citalopram dose-range: 20-40 mg/day (mean dose: 29.4 SD: 5.2).

Mirtazapine dose-range: 30-45 mg/day (mean dose: 37.2 SD: 5.7).

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Huang 2004

MethodsSix-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 29 participants.

Fluoxetine: 28 participants.

Citalopram dose-range: 20-40 mg/day.

Fluoxetine dose-range: 20-40 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17- Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Huang 2006

MethodsSix-week, randomised study.

ParticipantsIn and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Fluoxetine: 30 participants.

Citalopram dose-range: 10-40 mg/day (mean dose: 34 SD: 6.7).

Fluoxetine dose-range: 10-40 mg/day (mean dose: 33 SD: 6.5).

OutcomesChange in Hamilton Depression Rating Scale 17- Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Huang b 2006

MethodsEight-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 26 participants.

Fluoxetine: 25 participants.

Citalopram dose-range: 20-60 mg/day.

Fluoxetine dose-range: 20-60 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Juckel 2007

MethodsRandomized prospective study

Participants35 unmedicated in-patients with a DSM-IV or ICD-10 diagnosis of major depressive disorder

InterventionsCitalopram versus reboxetine (dose range not specified)

OutcomesChange on Hamilton Rating Scale for Depression

NotesWaiting for supplemental data about efficacy and tolerability from authors

Li 2004

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Amitriptyline: 30 participants.

Citalopram dose-rage: 20-40 mg/day (mean dose: 26 SD: 7.42).

Amitriptyline dose-range: 25-150 mg/day (mean dose116 SD: 24).

OutcomesChange in Hamilton Depression Rating Scale 21 item (HDRS-21) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Li 2005

MethodsSix-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 25 participants.

Venlafaxine: 25 participants.

Citalopram dose-range: 20-40 mg/day.

Venlafaxine dose-range: 25-250 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Li 2006

MethodsSix-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 28 participants.

Escitalopram: 28 participants.

Citalopram dose-range: 20-40 mg/day.

Escitalopram dose-range: 10-20 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Li DS 2006

MethodsSix-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 41 participants.

Paroxetinee: 41 participants.

Citalopram dose-rage: 20-40 mg/day.

Paroxetinee dose-range: 20-40 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Li X 2005

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Amitriptyline: 30 participants.

Citalopram dose-rage: 20-40 mg/day.

Amitriptyline dose-range: 50-200 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 24 Item (HDRS-24) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Li Z 2004

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 23 participants.

Amitriptyline: 23 participants.

Citalopram dose-rage: 20-40 mg/day.

Amitriptyline dose-range: 150-300 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Liang 2005

MethodsEight-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Fluoxetine: 30 participants.

Citalopram dose range: 10-60 mg/day.

Fluoxetine: dose range: 10-40 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 24 Item (HDRS-24) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Liang 2006

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 53 participants.

Mianserin: 53 participants.

Citalopram dose range: 10-40 mg/day (mean dose: 27.5 SD: 10.8).

Mianserin: dose range: 15-60 mg/day (mean dose: 40.3 SD: 12.2).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Lin 2001

MethodsSix-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-II-R criteria.

InterventionsCitalopram: 89 participants.

Amitriptyline: 89 participants.

Citalopram dose-rage: 20-40 mg/day (mean dose: 22 SD: 6).

Amitriptyline dose-range: 50-150 mg/day (mean dose: 100 SD: 10).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Liu 2006

MethodsEight-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-II-R criteria.

InterventionsCitalopram: 50 participants.

Amitriptyline: 50 participants.

Citalopram dose-rage: 20-40 mg/day.

Amitriptyline dose-range: 100-200 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 24 Item (HDRS-24) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Liu 2006d

MethodsRandomized study (likely)

ParticipantsPatients with senile depression

InterventionsCitalopram versus unclear comparator

OutcomesUnclear

NotesWaiting for abstract and full text to check for eligibility

Lu 2008

MethodsControl study.

ParticipantsPatients with depressive disorder.

InterventionsCitalopram

Doxepin

OutcomesUnclear (full text to retrieve).

Notes

Ma 2004

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD- III criteria.

InterventionsCitalopram: 30 participants.

Amitriptyline: 30 participants.

Citalopram dose-rage: 20 mg/day.

Amitriptyline dose-range: 25-175 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Moeller 1986

MethodsFour-week, double-blind study.

ParticipantsFemale in-patients with a Major Depressive Disorder (MDD) according to the DSM-III criteria, and with a pretreatment score of at least 18 on the Hamilton Depression Rating Scale-17 Item (HDRS-17).

Age range: 18-65 years.

Exclusion criteria: patients who did not give their informed consent, pregnant patients, patients with serious concomitant disease (heart, liver, kidney), patients with an organic cerebral syndrome, schizophrenics or patients with a paranoid psychosis, alcoholics or patients addicted to narcotics, patients with epilepsy, and patients having received MAO-inhibitors within the last 3 weeks.

InterventionsCitalopram: 14 participants.

Maprotiline: 13 participants.

Citalopram dose range: 40-60 mg/day.

Maprotiline dose range: 75-150 mg/day.

OutcomesPrimary outcome: plasma ratios of tryptophan (Trp) and Tyriosine (Tyr) to other large neutral amino acids.

NotesThis study was funded by Lundbeck (citalopram manufacturer).

One patient in maprotiline group committed suicide.

NCT00269334

MethodsRandomised, open-label study.

ParticipantsSelf-identified as of Taiwanese ethnic background, and report that both of their parents and all four of their grandparents are members of the same ethnic group;

non-responders: have a 21-item HDRS score of > 17; partial responders: have a 21-item HDRS score between 8 and 15; responders: have a 21-item HDRS score of < 7. Only the non-responder group will be included in Study II.

male or female, who, if of child-bearing potential, agrees to use effective contraception including the regular use of contraceptive pills, intra-uterine devises or abstinence;

age > 18;

capable of giving informed consent.

InterventionsCitalopram

Paroxetine

OutcomesStructured Clinical Interview for DSM-IV Disorders (SCID) at week baseline.

Hamilton Depression Rating Scale (HDRS) at week 1,2,4,6,8.

Beck Depression Inventory (BDI) at week 1,2,4,6,8.

Clinical Global Impression Scale (CGI) at week 1,2,4,6,8.

Patient's Global Improvement Scale (PGI) at week 1,2,4,6,8.

Treatment Emergent Symptoms Scale (TESS) at week 1,2,4,6,8.

Arizona Sexual Experience Scale (ASEX) at week 1,2,4,6,8.

Notes

NCT00993876

MethodsRandomised, open-label trial.

ParticipantsPatients with MDD according to DSM-IV criteria.

InterventionsCitalopram: 20-30 mg/day.

Reboxetine: 4-8 mg/day.

OutcomesCognitive performance with respect to cognitive flexibility, memory and attention.

Notes

Norra 2011

MethodsRandomised study.

ParticipantsUnmedicated patients with major depression and a healthy control group.

InterventionsCitalopram

Reboxetine

OutcomesComparison of Auditory Mismatch negativity (MMN) between unmedicated patients with major depression and a healthy control group, longitudinal examination of the patient group to investigate differential monoaminergic treatment effects of antidepressants on MMN.

Notes

Pan 2005

MethodsEight-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD- III criteria.

InterventionsCitalopram: 30 participants.

Paroxetine: 30 participants.

Venlafaxine: 30 participants.

Citalopram dose range: 20-60 mg/day.

Paroxetine dose range: 20-50 mg/day.

Venlafaxine dose range: 75-375 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Qiao 2005

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD- III criteria.

InterventionsCitalopram: 34 participants.

Paroxetinee: 34 participants.

Citalopram dose-rage: 30-60 mg/day.

Paroxetine dose-range: 20-60 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Qiu 2005

MethodsSix-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD- III criteria.

InterventionsCitalopram: 28 participants.

Amitriptyline: 28 participants.

Citalopram dose-rage: 20-40 mg/day.

Amitriptyline dose-range: 75-250 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Ren 2006

MethodsEight-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 54 participants.

Sertraline: 48 participants.

Citalopram dose range: 20-60 mg/day.

Sertraline dose range: 50-150 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 24 Item (HDRS-24) score from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Rutherford 2010

MethodsPreliminary results will be presented from a clinical trial and integrated functional Magnetic Resonance Imaging (fMRI) study randomising adult outpatients with MDD to 8 weeks of treatment in high vs. low expectancy conditions. Expectancy is measured using items 2 and 4 of the CES, which measure the subject’s expected likelihood and magnitude of improvement, respectively. Subjects are treated for 8 weeks with the study medication and are classified as responders (50% decrease from baseline HRSD) or remitters (HRSD < 7).

ParticipantsIncluded patients are men and women aged 18 to 65 years with unipolar MDD (DSM-IV) and 24-item HRSD score = 16.

InterventionsPatients are randomised to (1) Placebo-controlled Track (random assignment to escitalopram or placebo), or (2) Comparator Track (random assignment to escitalopram or citalopram) and are informed of their Track assignment but are blinded to their specific treatment assignment.

OutcomesWell-validated fMRI paradigms are used to investigate the activity of neural circuits underlying subjects’ response to emotional stimuli, reward processing, and memory retrieval.

Notes

Shi 2005

MethodsSix-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Maprotiline: 30 participants.

Citalopram dose range: 20 mg/day.

Maprotiline dose range: 100-200 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Song 2004

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 43 participants.

Fluoxetine: 46 participants.

Citalopram dose range: 20 mg/day.

Fluoxetine dose range: 20 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Tan 2004

MethodsSix-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 25 participants.

Amitriptyline: 26 participants.

Citalopram dose range: 20-40 mg/day.

Amitriptyline dose range: 100-200 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Tang 2005

MethodsEight-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 40 participants.

Amitriptyline: 40 participants.

Citalopram dose range: 20-60 mg/day (mean dose: 37.2 SD:17.4).

Amitriptyline dose range: 150-250 mg/day (mean dose: 191.3 SD: 37.8).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Tao 2005

MethodsSix-week, (likely) randomised study.

ParticipantsIn-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 33 participants.

Paroxetine: 30 participants.

Citalopram dose range: 20-40 mg/day.

Paroxetine dose range: 20-40 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Thomas 2008

MethodsTwelve-week, multi-centred randomised controlled trial.

ParticipantsPatients with depression according to ICD-10 criteria, recruited in primary care setting.

InterventionsCitalopram dose range: 20 mg/day.

Reboxetine dose range: 8 mg/day.

OutcomesChange in Beck Depression Inventory (BDI) from baseline to week 6.

NotesOnly study protocol available.

Wan 2006

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 35 participants.

Amitriptyline: 34 participants.

Citalopram dose range: 20 mg/day.

Amitriptyline dose range: 150mg/day .

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Wang 2003

MethodsSix-week, (likely) randomised study.

ParticipantsPatients with depression according to CCMD-III criteria.

InterventionsCitalopram: 39 participants.

Imipramine: 39 participants.

Citalopram dose range: 20-40 mg/day.

Imipramine dose range: 100-200 mg/day .

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Wang 2004

MethodsEight-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 42 participants.

Amitriptyline: 42 participants.

Citalopram dose range: 20-40 mg/day (mean dose: 28.6 SD: 5.2).

Amitriptyline dose range: 100-300 mg/day(mean dose: 220 SD: 48).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Wang 2006

MethodsEight-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 25 participants.

Mirtazapine: 25 participants.

Citalopram dose range: 20-40 mg/day.

mirtazapine dose range: 15-30 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Xu 2005

MethodsSix-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Amitriptyline: 30 participants.

Citalopram dose range: 20 - ? mg/day (the upper dose limit is unclear - mean dose: 25.5 SD: 15.5).

Amitriptyline dose range: 50 - ? mg/day (the upper dose limit is unclear - mean dose: 117.4 SD: 35.1).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment, number of patients who remitted.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Yu 2006

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 29 participants.

Venlafaxine: 29 participants.

Citalopram dose range: 10-40 mg/day (mean dose: 15 SD: 7.1).

Venlafaxine dose range: 50-200 mg/day (mean dose: 165 SD: 17).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Zhang 2005

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to DSM-IV criteria.

InterventionsCitalopram: 32 participants.

Venlafaxine: 34 participants.

Citalopram dose range: 10-40 mg/day.

Venlafaxine dose range: 50-225 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Zhang 2006

MethodsSix-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Maprotyline: 30 participants.

Citalopram dose range: 10-40 mg/day (mean dose: 21.90 SD:6.93).

Maprotyline dose range: 25-200 mg/day (mean dose: 141.52 SD: 30.4).

OutcomesChange in Hamilton Depression Rating Scale 17 Item (HDRS-17) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Zhao 2006

MethodsEight-week, (likely) randomised study.

ParticipantsIn- and out-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 30 participants.

Fluoxetine: 30 participants.

Citalopram dose range: 20-60 mg/day.

Fluoxetine dose range: 20-60 mg/day.

OutcomesChange in Hamilton Depression Rating Scale 24 Item (HDRS-24) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

Zhou 2005

MethodsSeven-week, (likely) randomised study.

ParticipantsOut-patients with depression according to CCMD-III criteria.

InterventionsCitalopram: 29 participants.

Venlafaxine: 28 participants.

Citalopram dose range: 20-40 mg/day.

Venlafaxine dose range: 50-300 mg/day.

OutcomesChange in Hamilton Depression Rating Scale (HDRS) score from baseline to endpoint, number of patients who responded to treatment.

NotesWaiting for translation from Chinese to English (only abstract available in English).

 
Characteristics of ongoing studies [ordered by study ID]
NCT01407094

Trial name or titleEstablishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (NCT01407094).

MethodsRandomised, double-blind study.

ParticipantsAdults, age 18-65.

Outpatients with a current diagnosis of nonpsychotic recurrent MDD per the SCID-I.

QIDS-SR score of ≥ 14 at Screening Visit and Randomization (Baseline) Visit.

No failed antidepressant trials of adequate dose and duration.

Agrees to, and is eligible for, all biomarkers procedures (EEG/psychological testing, MRI, and blood draws).

InterventionsCitalopram
Bupropion XL

Placebo

OutcomesPrimary Outcome Measure: HDRS score.

Starting dateJuly 2011.

Contact informationDavid W Morris, Ph.D. 214-648-0162 davidw.morris@utsouthwestern.edu
Ben T Kurian, M.D. 214-648-0158 benji.kurian@utsouthwestern.edu

Notes

NCT01473381

Trial name or titleSafety and Efficacy of Vilazodone in Major Depressive Disorder (NCT01473381).

MethodsRandomised, double-blind study.

ParticipantsPatients aged 18-70 years, with MDD (according to DSM-IV criteria).

The patient's current major depressive episode must be at least 8 weeks and no longer than 12 months in duration.

InterventionsVilazodone

Citalopram

Placebo

OutcomesPrimary Outcome Measure: MADRS score at 10 Weeks.

Starting dateNovember 2011.

Contact informationSandra Beaird, PhD 1-800-678-1605 ext 66297, info@forestpharm.com

Notes

 
Comparison 1. Failure to respond at endpoint (6-12 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs3888Odds Ratio (M-H, Random, 95% CI)1.10 [0.75, 1.63]

    1.1 Versus Amitriptyline
2416Odds Ratio (M-H, Random, 95% CI)1.44 [0.54, 3.87]

    1.2 Versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)1.00 [0.64, 1.58]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)1.05 [0.56, 1.96]

    2.1 Versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.67 [0.27, 1.62]

    2.2 Versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)1.31 [0.85, 2.04]

 3 Citalopram versus other SSRIs13Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
61806Odds Ratio (M-H, Random, 95% CI)1.47 [1.08, 2.02]

    3.2 Versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)1.03 [0.75, 1.43]

    3.3 Versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)0.90 [0.50, 1.62]

    3.4 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)0.65 [0.44, 0.96]

    3.5 Versus Sertraline
3551Odds Ratio (M-H, Random, 95% CI)0.53 [0.20, 1.42]

 4 Citalopram versus SNRI1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.91 [0.46, 1.78]

 5 Citalopram versus other conventional ADs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 Versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.76 [0.38, 1.52]

    5.2 Versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.63 [0.43, 0.91]

 6 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    6.1 Versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)0.93 [0.57, 1.52]

 
Comparison 2. Failure to respond (1-4 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs4751Odds Ratio (M-H, Random, 95% CI)0.95 [0.46, 1.98]

    1.1 versus Amitriptyline
3476Odds Ratio (M-H, Random, 95% CI)1.33 [0.76, 2.31]

    1.2 versus Imipramine
1275Odds Ratio (M-H, Random, 95% CI)0.45 [0.24, 0.86]

 2 Citalopram versus other SSRIs4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1143Odds Ratio (M-H, Random, 95% CI)1.46 [0.75, 2.82]

    2.2 Versus Fluoxetine
2416Odds Ratio (M-H, Random, 95% CI)0.89 [0.34, 2.34]

    2.3 Versus Sertraline
2245Odds Ratio (M-H, Random, 95% CI)1.14 [0.60, 2.15]

 3 Citalopram versus other conventional antidepressants2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.87 [0.27, 2.75]

 
Comparison 3. Failure to respond (16-24 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)1.09 [0.69, 1.72]

 2 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1357Odds Ratio (M-H, Random, 95% CI)1.04 [0.64, 1.68]

    2.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.72 [0.45, 1.17]

 3 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.89 [0.44, 1.82]

 4 Citalopram versus other conventional antidepressants1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.46 [0.30, 0.70]

 
Comparison 4. Failure to remission (1-4 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs3225Odds Ratio (M-H, Random, 95% CI)2.13 [0.98, 4.63]

    1.1 versus Amitriptyline
2111Odds Ratio (M-H, Random, 95% CI)2.29 [0.81, 6.48]

    1.2 versus Clomipramine
1114Odds Ratio (M-H, Random, 95% CI)1.95 [0.61, 6.23]

 2 Citalopram versus other SSRIs4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1143Odds Ratio (M-H, Random, 95% CI)1.53 [0.75, 3.15]

    2.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)0.78 [0.56, 1.10]

    2.3 Versus Sertraline
1145Odds Ratio (M-H, Random, 95% CI)1.86 [0.89, 3.88]

 3 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.75 [0.27, 2.05]

 
Comparison 5. Failure to remission (6-12 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs5256Odds Ratio (M-H, Random, 95% CI)1.32 [0.77, 2.26]

    1.1 versus Amitriptyline
2110Odds Ratio (M-H, Random, 95% CI)1.05 [0.48, 2.32]

    1.2 versus Nortriptyline
2101Odds Ratio (M-H, Random, 95% CI)2.06 [0.81, 5.29]

    1.3 versus Imipramine
145Odds Ratio (M-H, Random, 95% CI)1.09 [0.34, 3.51]

 2 Citalopram versus heterocyclics2156Odds Ratio (M-H, Random, 95% CI)0.66 [0.35, 1.24]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.71 [0.31, 1.60]

    2.2 versus Mianserin
160Odds Ratio (M-H, Random, 95% CI)0.58 [0.21, 1.62]

 3 Citalopram versus other SSRIs10Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
51427Odds Ratio (M-H, Random, 95% CI)1.94 [1.16, 3.26]

    3.2 Versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)0.94 [0.63, 1.42]

    3.3 Versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)0.56 [0.23, 1.34]

    3.4 Versus Sertraline
2151Odds Ratio (M-H, Random, 95% CI)0.56 [0.29, 1.08]

 4 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.66 [0.34, 1.26]

 5 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.59 [0.38, 0.92]

 
Comparison 6. Failure to remission (16-24 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1357Odds Ratio (M-H, Random, 95% CI)1.17 [0.74, 1.84]

 2 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.77 [0.35, 1.70]

 3 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.43 [0.28, 0.65]

 
Comparison 7. Standardised mean difference (1-4 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs4174Std. Mean Difference (IV, Random, 95% CI)0.10 [-0.20, 0.40]

    1.1 versus Amitriptyline
291Std. Mean Difference (IV, Random, 95% CI)0.03 [-0.38, 0.44]

    1.2 versus Nortriptyline
283Std. Mean Difference (IV, Random, 95% CI)0.22 [-0.35, 0.79]

 2 Citalopram versus heterocyclics2150Std. Mean Difference (IV, Random, 95% CI)-0.22 [-0.81, 0.37]

    2.1 versus Maprotiline
192Std. Mean Difference (IV, Random, 95% CI)0.06 [-0.35, 0.47]

    2.2 versus Mianserin
158Std. Mean Difference (IV, Random, 95% CI)-0.55 [-1.07, -0.02]

 3 Citalopram versus other SSRIs9Std. Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 versus Escitalopram
3657Std. Mean Difference (IV, Random, 95% CI)0.09 [-0.07, 0.24]

    3.2 versus Fluoxetine
4723Std. Mean Difference (IV, Random, 95% CI)-0.15 [-0.30, -0.01]

    3.3 versus Sertraline
3287Std. Mean Difference (IV, Random, 95% CI)-0.25 [-0.76, 0.25]

 4 Citalopram versus other conventional ADs1Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 versus Reboxetine
1317Mean Difference (IV, Random, 95% CI)-1.5 [-2.76, -0.24]

 
Comparison 8. Standardised mean difference at endpoint (6-12 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs5402Std. Mean Difference (IV, Random, 95% CI)0.06 [-0.15, 0.26]

    1.1 versus Amitriptyline
144Std. Mean Difference (IV, Random, 95% CI)-0.07 [-0.66, 0.53]

    1.2 versus Imipramine
2289Std. Mean Difference (IV, Random, 95% CI)-0.03 [-0.27, 0.22]

    1.3 versus Nortriptyline
269Std. Mean Difference (IV, Random, 95% CI)0.46 [-0.02, 0.94]

 2 Citalopram versus heterocyclics2131Std. Mean Difference (IV, Random, 95% CI)-0.18 [-0.65, 0.29]

    2.1 versus Maprotiline
173Std. Mean Difference (IV, Random, 95% CI)0.04 [-0.42, 0.50]

    2.2 versus Mianserin
158Std. Mean Difference (IV, Random, 95% CI)-0.44 [-0.96, 0.09]

 3 Citalopram versus other SSRIs163610Std. Mean Difference (IV, Random, 95% CI)-.00 [-0.11, 0.10]

    3.1 versus Escitalopram
71872Std. Mean Difference (IV, Random, 95% CI)0.16 [0.05, 0.27]

    3.2 versus Fluoxetine
3672Std. Mean Difference (IV, Random, 95% CI)-0.17 [-0.46, 0.11]

    3.3 versus Fluvoxamine
1162Std. Mean Difference (IV, Random, 95% CI)-0.19 [-0.50, 0.12]

    3.4 versus Paroxetine
1201Std. Mean Difference (IV, Random, 95% CI)-0.11 [-0.39, 0.16]

    3.5 versus Sertraline
4703Std. Mean Difference (IV, Random, 95% CI)-0.13 [-0.31, 0.04]

 4 Citalopram versus SNRIs1Mean Difference (IV, Random, 95% CI)Subtotals only

    4.1 versus Venlafaxine XR
1148Mean Difference (IV, Random, 95% CI)-0.5 [-2.93, 1.93]

 5 Citalopram versus MAOIs or newer ADs1Mean Difference (IV, Random, 95% CI)Subtotals only

    5.1 versus Moclobemide
140Mean Difference (IV, Random, 95% CI)-4.6 [-8.28, -0.92]

 6 Citalopram versus other conventional ADs3Std. Mean Difference (IV, Random, 95% CI)Subtotals only

    6.1 versus Mirtazapine
1269Std. Mean Difference (IV, Random, 95% CI)-0.02 [-0.26, 0.22]

    6.2 versus Reboxetine
2866Std. Mean Difference (IV, Random, 95% CI)-0.15 [-0.33, 0.04]

 
Comparison 9. Standardised mean difference (16-24 weeks)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1Mean Difference (IV, Random, 95% CI)Subtotals only

    1.1 versus Imipramine
1168Mean Difference (IV, Random, 95% CI)0.90 [-1.02, 2.82]

 2 Citalopram versus SNRIs1Mean Difference (IV, Random, 95% CI)Subtotals only

    2.1 versus Venlafaxine XR
1148Mean Difference (IV, Random, 95% CI)0.0 [-2.61, 2.61]

 3 Citalopram versus other conventional ADs1Mean Difference (IV, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
1320Mean Difference (IV, Random, 95% CI)-1.80 [-3.62, 0.02]

 
Comparison 10. Failure to complete (any cause)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs81209Odds Ratio (M-H, Random, 95% CI)0.81 [0.61, 1.07]

    1.1 versus Amitriptyline
4535Odds Ratio (M-H, Random, 95% CI)0.70 [0.47, 1.04]

    1.2 versus Clomipramine
1114Odds Ratio (M-H, Random, 95% CI)1.63 [0.61, 4.36]

    1.3 versus Imipramine
2517Odds Ratio (M-H, Random, 95% CI)0.88 [0.55, 1.41]

    1.4 versus Nortriptyline
143Odds Ratio (M-H, Random, 95% CI)0.63 [0.19, 2.08]

 2 Citalopram versus heterocyclics3492Odds Ratio (M-H, Random, 95% CI)0.75 [0.46, 1.22]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.82 [0.35, 1.96]

    2.2 versus Mianserin
2396Odds Ratio (M-H, Random, 95% CI)0.72 [0.40, 1.29]

 3 Citalopram versus other SSRIs18Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
82206Odds Ratio (M-H, Random, 95% CI)0.92 [0.64, 1.31]

    3.2 Versus Fluoxetine
4799Odds Ratio (M-H, Random, 95% CI)1.16 [0.81, 1.67]

    3.3 Versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)0.71 [0.37, 1.33]

    3.4 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.01 [0.62, 1.63]

    3.5 Versus Sertraline
5911Odds Ratio (M-H, Random, 95% CI)0.74 [0.51, 1.08]

 4 Citalopram versus other conventional ADs5Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Reboxetine
41095Odds Ratio (M-H, Random, 95% CI)0.71 [0.42, 1.21]

    4.2 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.42 [0.18, 1.01]

 5 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)3.01 [0.93, 9.72]

 
Comparison 11. Failure to complete (side effects)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs81216Odds Ratio (M-H, Random, 95% CI)0.54 [0.38, 0.78]

    1.1 versus Amitriptyline
3484Odds Ratio (M-H, Random, 95% CI)0.54 [0.34, 0.87]

    1.2 versus Clomipramine
1114Odds Ratio (M-H, Random, 95% CI)0.10 [0.01, 1.97]

    1.3 versus Imipramine
2517Odds Ratio (M-H, Random, 95% CI)0.65 [0.36, 1.19]

    1.4 versus Nortriptyline
2101Odds Ratio (M-H, Random, 95% CI)0.15 [0.02, 1.34]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)0.50 [0.21, 1.18]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.19 [0.01, 4.10]

    2.2 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.54 [0.22, 1.32]

 3 Citalopram versus other SSRIs15Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
71989Odds Ratio (M-H, Random, 95% CI)1.09 [0.65, 1.82]

    3.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)1.46 [0.80, 2.67]

    3.3 Versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)0.56 [0.28, 1.11]

    3.4 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)0.87 [0.36, 2.09]

    3.5 Versus Sertraline
4860Odds Ratio (M-H, Random, 95% CI)0.69 [0.43, 1.09]

 4 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.49 [0.12, 2.02]

 5 Citalopram versus other conventional ADs4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.82 [0.21, 3.12]

    5.2 versus Reboxetine
3494Odds Ratio (M-H, Random, 95% CI)0.40 [0.13, 1.27]

 
Comparison 12. Failure to complete (inefficacy)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs91267Odds Ratio (M-H, Random, 95% CI)1.47 [0.84, 2.57]

    1.1 versus Amitriptyline
4535Odds Ratio (M-H, Random, 95% CI)0.83 [0.33, 2.09]

    1.2 versus Clomipramine
1114Odds Ratio (M-H, Random, 95% CI)2.48 [0.72, 8.59]

    1.3 versus Imipramine
2517Odds Ratio (M-H, Random, 95% CI)1.64 [0.24, 11.24]

    1.4 versus Nortriptyline
2101Odds Ratio (M-H, Random, 95% CI)2.55 [0.76, 8.53]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)0.63 [0.24, 1.69]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.64 [0.17, 2.42]

    2.2 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.63 [0.15, 2.68]

 3 Citalopram versus other SSRIs14Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
82206Odds Ratio (M-H, Random, 95% CI)0.80 [0.38, 1.66]

    3.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)1.15 [0.64, 2.08]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)0.57 [0.13, 2.42]

    3.4 Versus Sertraline
3760Odds Ratio (M-H, Random, 95% CI)0.73 [0.34, 1.60]

 4 Citalopram versus other conventional ADs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.25 [0.03, 2.28]

    4.2 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.66 [0.17, 2.57]

 
Comparison 13. SE - Subjects with at least one TEAEs

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs71088Odds Ratio (M-H, Random, 95% CI)0.65 [0.30, 1.41]

    1.1 versus Amitriptyline
4528Odds Ratio (M-H, Random, 95% CI)0.43 [0.28, 0.65]

    1.2 versus Imipramine
2517Odds Ratio (M-H, Random, 95% CI)1.82 [1.14, 2.89]

    1.3 versus Nortriptyline
143Odds Ratio (M-H, Random, 95% CI)0.94 [0.20, 4.39]

 2 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)0.84 [0.52, 1.37]

    2.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.84 [0.52, 1.37]

 3 Citalopram versus other SSRIs15Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
71979Odds Ratio (M-H, Random, 95% CI)1.20 [0.97, 1.47]

    3.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)1.10 [0.81, 1.47]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.34 [0.83, 2.18]

    3.4 Versus Sertraline
5902Odds Ratio (M-H, Random, 95% CI)0.67 [0.39, 1.16]

 4 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.46 [0.24, 0.88]

 5 Citalopram versus MAOIs or newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)0.69 [0.20, 2.35]

 6 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    6.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)1.22 [0.73, 2.04]

    6.2 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.64 [0.42, 0.97]

 7 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    7.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)1.69 [1.01, 2.83]

 
Comparison 14. SE - Abdominal pain

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

    1.2 Versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)1.57 [0.55, 4.53]

 
Comparison 15. SE - Accidental injury

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1357Odds Ratio (M-H, Random, 95% CI)0.37 [0.11, 1.21]

 
Comparison 16. SE - Aggressive behaviour

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

 
Comparison 17. SE - Anorexia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
2448Odds Ratio (M-H, Random, 95% CI)0.64 [0.06, 7.29]

 
Comparison 18. SE - Anxiety/agitation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs135Odds Ratio (M-H, Random, 95% CI)1.4 [0.35, 5.54]

    1.1 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)1.4 [0.35, 5.54]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)0.91 [0.16, 5.16]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.19 [0.01, 4.10]

    2.2 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)1.49 [0.58, 3.81]

 3 Citalopram versus other SSRIs4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
2437Odds Ratio (M-H, Random, 95% CI)0.79 [0.07, 9.51]

    3.2 Versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)1.04 [0.50, 2.16]

    3.3 Versus Sertraline
1145Odds Ratio (M-H, Random, 95% CI)2.96 [0.30, 29.12]

 
Comparison 19. SE - Appetite increased

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.16 [0.03, 0.72]

 
Comparison 20. SE - Asthenia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Amitriptyline
152Odds Ratio (M-H, Random, 95% CI)0.50 [0.11, 2.35]

    1.2 Versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)0.6 [0.09, 4.01]

 2 Citalopram versus other SSRIs4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.93 [0.13, 6.72]

    2.2 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.69 [0.96, 3.00]

    2.3 Versus Sertraline
2442Odds Ratio (M-H, Random, 95% CI)0.39 [0.11, 1.37]

 
Comparison 21. SE - Back pain

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)0.62 [0.22, 1.75]

    1.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.62 [0.22, 1.75]

 2 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
2605Odds Ratio (M-H, Random, 95% CI)1.36 [0.34, 5.51]

    2.2 Versus Fluoxetine
1357Odds Ratio (M-H, Random, 95% CI)12.04 [0.66, 219.46]

 
Comparison 22. SE - Brest surgery

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

 
Comparison 23. SE - Bronchitis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1357Odds Ratio (M-H, Random, 95% CI)0.28 [0.07, 1.02]

    1.2 Versus Fluoxetine
1357Odds Ratio (M-H, Random, 95% CI)0.75 [0.23, 2.42]

 
Comparison 24. SE - Chest pain

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

 
Comparison 25. SE - Chicken pox

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

 
Comparison 26. SE - Common cold

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.67 [0.11, 4.11]

 
Comparison 27. SE - Concentration decrease

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 2 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.50 [0.04, 5.53]

 3 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.68 [0.11, 4.13]

 
Comparison 28. SE - Confusion

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Amitriptyline
152Odds Ratio (M-H, Random, 95% CI)0.32 [0.06, 1.83]

    1.2 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)3.36 [0.13, 88.39]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.51 [0.05, 5.69]

 
Comparison 29. SE - Conjunctivitis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs151Odds Ratio (M-H, Random, 95% CI)2.77 [0.11, 71.35]

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)2.77 [0.11, 71.35]

 
Comparison 30. SE - Constipation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs61018Odds Ratio (M-H, Random, 95% CI)0.36 [0.24, 0.55]

    1.1 versus Amitriptyline
3468Odds Ratio (M-H, Random, 95% CI)0.46 [0.23, 0.90]

    1.2 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.31 [0.18, 0.53]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.43 [0.09, 2.09]

 2 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)0.70 [0.24, 2.00]

    2.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.70 [0.24, 2.00]

 3 Citalopram versus other SSRIs4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

    3.2 Versus Fluoxetine
1357Odds Ratio (M-H, Random, 95% CI)0.35 [0.07, 1.74]

    3.3 Versus Sertraline
2442Odds Ratio (M-H, Random, 95% CI)0.65 [0.23, 1.88]

 4 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)2.64 [0.50, 14.07]

 5 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.06 [0.00, 0.90]

 
Comparison 31. SE - Craving for sweets

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)5.22 [0.24, 111.55]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)5.22 [0.24, 111.55]

 
Comparison 32. SE - Decreased weight

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)0.62 [0.25, 1.50]

    1.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)2.23 [0.98, 5.05]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.12 [0.02, 1.00]

 
Comparison 33. SE - Dermatological problems

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs151Odds Ratio (M-H, Random, 95% CI)0.88 [0.05, 14.96]

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)0.88 [0.05, 14.96]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

 3 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
1219Odds Ratio (M-H, Random, 95% CI)2.0 [0.18, 22.38]

    3.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.21 [0.36, 4.02]

 4 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)1.57 [0.43, 5.72]

 
Comparison 34. SE - Diarrhoea

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs295Odds Ratio (M-H, Random, 95% CI)1.27 [0.26, 6.16]

    1.1 versus Amitriptyline
152Odds Ratio (M-H, Random, 95% CI)1.92 [0.16, 22.58]

    1.2 versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)0.95 [0.12, 7.44]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)1.0 [0.14, 7.40]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.0 [0.14, 7.40]

 3 Citalopram versus other SSRIs8Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
41247Odds Ratio (M-H, Random, 95% CI)1.22 [0.78, 1.92]

    3.2 Versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)2.11 [0.34, 13.22]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)0.73 [0.41, 1.32]

    3.4 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.63 [0.29, 1.37]

 4 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)2.13 [0.63, 7.24]

    4.2 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.03 [0.20, 5.17]

 
Comparison 35. SE - Dizziness

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs5546Odds Ratio (M-H, Random, 95% CI)0.59 [0.27, 1.27]

    1.1 versus Amitriptyline
3468Odds Ratio (M-H, Random, 95% CI)0.47 [0.15, 1.44]

    1.2 versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)0.35 [0.10, 1.22]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)1.82 [0.44, 7.48]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)0.77 [0.22, 2.68]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.47 [0.43, 5.00]

    2.2 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.41 [0.13, 1.33]

 3 Citalopram versus other SSRIs6Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
51136Odds Ratio (M-H, Random, 95% CI)0.88 [0.43, 1.81]

    3.2 Versus Sertraline
2545Odds Ratio (M-H, Random, 95% CI)0.76 [0.41, 1.39]

 4 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)0.75 [0.16, 3.47]

 5 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.49 [0.18, 1.35]

    5.2 versus Reboxetine
1101Odds Ratio (M-H, Random, 95% CI)0.75 [0.31, 1.81]

 
Comparison 36. SE - Dry mouth

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs71078Odds Ratio (M-H, Random, 95% CI)0.25 [0.18, 0.35]

    1.1 versus Amitriptyline
4528Odds Ratio (M-H, Random, 95% CI)0.17 [0.10, 0.28]

    1.2 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.32 [0.21, 0.50]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.44 [0.11, 1.70]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.73 [0.30, 1.79]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.73 [0.30, 1.79]

 3 Citalopram versus other SSRIs10Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
51457Odds Ratio (M-H, Random, 95% CI)0.98 [0.60, 1.62]

    3.2 Versus Fluoxetine
2416Odds Ratio (M-H, Random, 95% CI)0.49 [0.02, 11.57]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.03 [0.60, 1.79]

    3.4 Versus Sertraline
2442Odds Ratio (M-H, Random, 95% CI)0.65 [0.35, 1.20]

 4 Citalopram versus SNRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 Versus Venlafaxine XR
1151Odds Ratio (M-H, Random, 95% CI)1.16 [0.42, 3.18]

 5 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.52 [0.25, 1.10]

 
Comparison 37. SE - Dyspepsia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)2.04 [0.18, 23.32]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)2.04 [0.18, 23.32]

 2 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1219Odds Ratio (M-H, Random, 95% CI)3.0 [0.12, 74.45]

 
Comparison 38. SE - Dyspnea

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.33 [0.01, 8.22]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.33 [0.01, 8.22]

 
Comparison 39. SE - Emotional indifference

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)2.01 [0.18, 22.35]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.25 [0.03, 2.28]

 
Comparison 40. SE - Enuresis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

 
Comparison 41. SE - Exacerbation of depressive disorder

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

 
Comparison 42. SE - Fatigue

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1365Odds Ratio (M-H, Random, 95% CI)0.55 [0.20, 1.53]

    1.1 versus Amitriptyline
1365Odds Ratio (M-H, Random, 95% CI)0.55 [0.20, 1.53]

 2 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)0.21 [0.06, 0.76]

    2.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.21 [0.06, 0.76]

 3 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
2467Odds Ratio (M-H, Random, 95% CI)0.31 [0.12, 0.84]

 4 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)1.10 [0.54, 2.25]

 
Comparison 43. SE - Feeling of numbness

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)5.22 [0.24, 111.55]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)5.22 [0.24, 111.55]

 
Comparison 44. SE - Forgetfulness

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.78 [0.51, 6.17]

 
Comparison 45. SE - Gastrointestinal

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs3146Odds Ratio (M-H, Random, 95% CI)0.77 [0.28, 2.15]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Random, 95% CI)0.45 [0.10, 2.07]

    1.2 versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)1.2 [0.30, 4.74]

 2 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
2375Odds Ratio (M-H, Random, 95% CI)1.14 [0.54, 2.40]

    2.2 Versus Sertraline
2545Odds Ratio (M-H, Random, 95% CI)0.62 [0.30, 1.30]

 3 Citalopram versus MAOIs or newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)1.13 [0.28, 4.47]

 4 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)2.41 [1.12, 5.18]

 
Comparison 46. SE - Headache

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs6606Odds Ratio (M-H, Random, 95% CI)1.37 [0.78, 2.42]

    1.1 versus Amitriptyline
4528Odds Ratio (M-H, Random, 95% CI)1.25 [0.65, 2.42]

    1.2 versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)3.56 [0.63, 20.15]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)1.08 [0.25, 4.70]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)1.27 [0.62, 2.60]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)2.14 [0.50, 9.12]

    2.2 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)1.07 [0.46, 2.45]

 3 Citalopram versus other SSRIs11Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
51261Odds Ratio (M-H, Random, 95% CI)1.08 [0.64, 1.81]

    3.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)0.90 [0.51, 1.60]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.24 [0.79, 1.96]

    3.4 Versus Sertraline
3587Odds Ratio (M-H, Random, 95% CI)0.55 [0.33, 0.91]

 4 Citalopram versus IMAOs or newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)0.16 [0.01, 3.64]

 5 Citalopram versusother conventional ADs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)1.59 [0.75, 3.37]

    5.2 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.50 [0.25, 1.00]

 
Comparison 47. SE - Hot flush

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

 
Comparison 48. SE - Hypertonia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

 
Comparison 49. SE - Hypotension

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)0.38 [0.19, 0.75]

 2 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

 
Comparison 50. SE - Increased dream activity

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.5 [0.17, 1.49]

 
Comparison 51. SE - Increased salivation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus older ADs196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 2 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)3.02 [0.12, 74.46]

 3 Citalopram versus newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.20 [0.01, 4.27]

 
Comparison 52. SE - Infection

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)0.86 [0.43, 1.72]

 
Comparison 53. SE - Influenza-like symptoms

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Fluoxetine
1357Odds Ratio (M-H, Random, 95% CI)0.35 [0.07, 1.74]

 2 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.43 [0.11, 1.69]

    2.2 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.17 [0.44, 3.09]

 
Comparison 54. SE - Insomnia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs2532Odds Ratio (M-H, Random, 95% CI)1.64 [0.58, 4.69]

    1.1 versus Amitriptyline
160Odds Ratio (M-H, Random, 95% CI)3.78 [0.70, 20.53]

    1.2 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)1.17 [0.52, 2.59]

 2 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)2.94 [1.20, 7.25]

    2.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)2.94 [1.20, 7.25]

 3 Citalopram versus other SSRIs12Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
61613Odds Ratio (M-H, Random, 95% CI)0.88 [0.60, 1.30]

    3.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)1.16 [0.60, 2.23]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)0.92 [0.53, 1.59]

    3.4 Versus Sertraline
3587Odds Ratio (M-H, Random, 95% CI)1.54 [0.82, 2.91]

 4 Citalopram versus MAOIs or newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)0.29 [0.01, 7.51]

 5 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.31 [0.05, 1.99]

 
Comparison 55. SE - Irritability

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1472Odds Ratio (M-H, Random, 95% CI)0.53 [0.26, 1.09]

    1.1 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)0.53 [0.26, 1.09]

 
Comparison 56. SE - Loss of hair

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs151Odds Ratio (M-H, Random, 95% CI)2.77 [0.11, 71.35]

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)2.77 [0.11, 71.35]

 
Comparison 57. SE - Memory impairment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)4.73 [0.23, 99.47]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.68 [0.11, 4.13]

 
Comparison 58. SE - Meteorism

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs151Odds Ratio (M-H, Random, 95% CI)0.28 [0.01, 7.33]

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)0.28 [0.01, 7.33]

 
Comparison 59. SE - Musculoskeletal and connective tissue disorders

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)0.85 [0.25, 2.87]

 
Comparison 60. SE - Nasal congestion

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.0 [0.06, 16.46]

 
Comparison 61. SE - Nausea/vomiting

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs61027Odds Ratio (M-H, Random, 95% CI)1.78 [0.96, 3.30]

    1.1 versus Amitriptyline
3477Odds Ratio (M-H, Random, 95% CI)2.44 [1.27, 4.66]

    1.2 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.98 [0.55, 1.73]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)7.11 [1.23, 40.98]

 2 Citalopram versus heterocyclics2432Odds Ratio (M-H, Random, 95% CI)2.82 [0.60, 13.23]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)12.26 [0.66, 228.27]

    2.2 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)1.88 [0.89, 3.97]

 3 Citalopram versus other SSRIs12Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
72055Odds Ratio (M-H, Random, 95% CI)0.92 [0.49, 1.74]

    3.2 Versus Fluoxetine
3732Odds Ratio (M-H, Random, 95% CI)1.46 [0.91, 2.35]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.15 [0.67, 1.95]

    3.4 Versus Sertraline
142Odds Ratio (M-H, Random, 95% CI)0.71 [0.14, 3.64]

 4 Citalopram versus other conventional ADs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)2.24 [1.12, 4.49]

    4.2 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)3.46 [0.40, 29.92]

 
Comparison 62. SE - Nervousness

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Fluoxetine
1316Odds Ratio (M-H, Random, 95% CI)1.21 [0.36, 4.04]

 
Comparison 63. SE - Orthostatic symptoms

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)1.0 [0.19, 5.22]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)1.0 [0.19, 5.22]

 2 Citalopram versus newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.44 [0.13, 1.47]

 
Comparison 64. SE - Pain (general)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)0.70 [0.24, 2.00]

    1.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.70 [0.24, 2.00]

 
Comparison 65. SE - Palpitations

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs3138Odds Ratio (M-H, Fixed, 95% CI)0.54 [0.21, 1.41]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Fixed, 95% CI)0.36 [0.10, 1.24]

    1.2 versus Nortriptyline
135Odds Ratio (M-H, Fixed, 95% CI)1.08 [0.22, 5.22]

 2 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

    2.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.35 [0.46, 3.96]

 
Comparison 66. SE - Panic attack

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

 
Comparison 67. SE - Paraesthesia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.03 [0.29, 3.62]

 
Comparison 68. SE - Pharyngitis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

 
Comparison 69. SE - Pruritus

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)2.08 [0.41, 10.53]

 2 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

    2.2 Versus Fluoxetine
1316Odds Ratio (M-H, Random, 95% CI)0.39 [0.07, 2.05]

 
Comparison 70. SE - Rash

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Amitriptyline
152Odds Ratio (M-H, Random, 95% CI)0.92 [0.05, 15.59]

 2 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Escitalopram
1219Odds Ratio (M-H, Random, 95% CI)3.0 [0.12, 74.45]

 3 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.51 [0.09, 2.81]

 
Comparison 71. SE - Reduced salivation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.31 [0.14, 0.67]

 
Comparison 72. SE - Sedation/drowsiness

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs2112Odds Ratio (M-H, Random, 95% CI)0.25 [0.09, 0.70]

    1.1 versus Amitriptyline
2112Odds Ratio (M-H, Random, 95% CI)0.25 [0.09, 0.70]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.62 [0.20, 1.90]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.62 [0.20, 1.90]

 3 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.31 [0.01, 7.65]

    3.2 Versus Fluoxetine
159Odds Ratio (M-H, Random, 95% CI)1.04 [0.14, 7.90]

    3.3 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.90 [0.36, 2.25]

 4 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.73 [0.29, 1.88]

    4.2 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.91 [0.34, 2.41]

 
Comparison 73. SE - Rhinitis

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
3922Odds Ratio (M-H, Random, 95% CI)0.87 [0.40, 1.87]

 
Comparison 74. SE - Restlessness

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs3146Odds Ratio (M-H, Random, 95% CI)0.69 [0.24, 1.99]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Random, 95% CI)0.71 [0.18, 2.82]

    1.2 versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)0.67 [0.13, 3.44]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.18 [0.02, 1.63]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.18 [0.02, 1.63]

 
Comparison 75. SE - Sexual problems

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Anorgasmia1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.96 [0.97, 3.97]

 2 Erectile dysfunction2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Escitalopram
1317Odds Ratio (M-H, Random, 95% CI)0.19 [0.01, 4.02]

    2.2 versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)2.38 [0.61, 9.34]

 3 Increased sexual desire2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Escitalopram
1248Odds Ratio (M-H, Random, 95% CI)1.15 [0.43, 3.10]

    3.2 versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)2.08 [0.82, 5.26]

 4 Loss of sexual interest3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)0.29 [0.01, 7.51]

    4.2 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.73 [0.41, 7.37]

    4.3 versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.83 [0.41, 1.66]

 5 Orgastic dysfunction1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)3.74 [1.56, 8.95]

 6 Other sexual problems7Odds Ratio (M-H, Random, 95% CI)Subtotals only

    6.1 versus Escitalopram
41015Odds Ratio (M-H, Random, 95% CI)0.72 [0.36, 1.43]

    6.2 versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.15 [0.50, 2.62]

    6.3 versus Reboxetine
1101Odds Ratio (M-H, Random, 95% CI)8.65 [1.86, 40.22]

    6.4 versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.67 [0.68, 4.12]

 
Comparison 76. SE - Sleepiness/somnolence

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs5966Odds Ratio (M-H, Random, 95% CI)0.49 [0.33, 0.74]

    1.1 versus Amitriptyline
2416Odds Ratio (M-H, Random, 95% CI)0.45 [0.24, 0.85]

    1.2 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.48 [0.27, 0.83]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.9 [0.24, 3.41]

 2 Citalopram versus heterocyclics1336Odds Ratio (M-H, Random, 95% CI)0.20 [0.04, 0.94]

    2.1 versus Mianserin
1336Odds Ratio (M-H, Random, 95% CI)0.20 [0.04, 0.94]

 3 Citalopram versus other SSRIs7Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
3859Odds Ratio (M-H, Random, 95% CI)0.75 [0.34, 1.64]

    3.2 Versus Fluoxetine
1316Odds Ratio (M-H, Random, 95% CI)1.42 [0.44, 4.57]

    3.3 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)1.64 [0.92, 2.90]

    3.4 Versus Sertraline
2442Odds Ratio (M-H, Random, 95% CI)0.68 [0.31, 1.51]

 4 Citalopram versus MAOIs or newer ADs142Odds Ratio (M-H, Random, 95% CI)2.86 [0.11, 74.31]

    4.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)2.86 [0.11, 74.31]

 5 Citalopram versus other conventional ADs1357Odds Ratio (M-H, Random, 95% CI)2.46 [0.63, 9.66]

    5.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)2.46 [0.63, 9.66]

 
Comparison 77. SE - Sweating

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs5653Odds Ratio (M-H, Random, 95% CI)0.49 [0.31, 0.77]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Random, 95% CI)0.41 [0.12, 1.49]

    1.2 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.50 [0.30, 0.83]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.56 [0.14, 2.21]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)2.2 [0.62, 7.87]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)2.2 [0.62, 7.87]

 3 Citalopram versus other SSRIs6Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
3859Odds Ratio (M-H, Random, 95% CI)0.83 [0.39, 1.78]

    3.2 Versus Fluoxetine
1316Odds Ratio (M-H, Random, 95% CI)3.08 [0.61, 15.49]

    3.3 Versus Sertraline
2442Odds Ratio (M-H, Random, 95% CI)1.32 [0.76, 2.27]

 4 Citalopram versus other conventional ADs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)7.91 [2.29, 27.29]

    4.2 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.38 [0.16, 0.90]

 
Comparison 78. SE - Syncope

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs151Odds Ratio (M-H, Random, 95% CI)0.28 [0.01, 7.33]

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)0.28 [0.01, 7.33]

 2 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 Versus Paroxetine
1406Odds Ratio (M-H, Random, 95% CI)2.90 [0.12, 71.57]

 
Comparison 79. SE - Tachycardia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs2515Odds Ratio (M-H, Random, 95% CI)0.36 [0.13, 0.99]

    1.1 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.36 [0.13, 0.99]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.57 [0.13, 2.55]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.57 [0.13, 2.55]

 3 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Escitalopram
1248Odds Ratio (M-H, Random, 95% CI)0.34 [0.01, 8.33]

 4 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.03 [0.20, 5.17]

 
Comparison 80. SE - Taste abnormalities

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs151Odds Ratio (M-H, Random, 95% CI)0.28 [0.01, 7.33]

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)0.28 [0.01, 7.33]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 
Comparison 81. SE - Tension

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Fluoxetine
1316Odds Ratio (M-H, Random, 95% CI)1.0 [0.32, 3.17]

    1.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.17 [0.39, 3.55]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.38 [0.30, 6.26]

 
Comparison 82. SE - Tremor

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs5653Odds Ratio (M-H, Random, 95% CI)0.46 [0.28, 0.76]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Random, 95% CI)0.51 [0.15, 1.75]

    1.2 versus Imipramine
2515Odds Ratio (M-H, Random, 95% CI)0.45 [0.25, 0.80]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.48 [0.11, 2.10]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.58 [0.18, 1.93]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.58 [0.18, 1.93]

 3 Citalopram versus other SSRIs2Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)0.10 [0.01, 1.89]

    3.2 Versus Sertraline
142Odds Ratio (M-H, Random, 95% CI)0.12 [0.01, 2.54]

 4 Citalopram versus MAOIs or newer ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Moclobemide
142Odds Ratio (M-H, Random, 95% CI)1.9 [0.16, 22.72]

 5 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    5.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.40 [0.08, 2.11]

 
Comparison 83. SE - Urination problems

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs3138Odds Ratio (M-H, Random, 95% CI)0.26 [0.06, 1.12]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Random, 95% CI)0.23 [0.04, 1.49]

    1.2 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.31 [0.03, 3.34]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)0.19 [0.01, 4.10]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)0.19 [0.01, 4.10]

 3 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)1.52 [0.42, 5.45]

 4 Citalopram versus other conventional ADs2458Odds Ratio (M-H, Random, 95% CI)0.18 [0.01, 5.61]

    4.1 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)0.18 [0.01, 5.61]

 
Comparison 84. SE - Upper respiratory tract infection

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
1248Odds Ratio (M-H, Random, 95% CI)0.66 [0.26, 1.66]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.68 [0.54, 5.23]

 
Comparison 85. SE - Vertigo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Fluoxetine
1316Odds Ratio (M-H, Random, 95% CI)2.40 [0.61, 9.43]

 2 Citalopram versus other conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)1.30 [0.50, 3.38]

 3 Citalopram versus non-conventional ADs1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 versus Hypericum (St. John's wort)
1258Odds Ratio (M-H, Random, 95% CI)6.12 [1.33, 28.17]

 
Comparison 86. SE - Visual problems (accommodation disorders, blurred vision, detached retina, mydriasis)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus TCAs4181Odds Ratio (M-H, Random, 95% CI)0.30 [0.13, 0.69]

    1.1 versus Amitriptyline
2103Odds Ratio (M-H, Random, 95% CI)0.14 [0.02, 0.82]

    1.2 versus Imipramine
143Odds Ratio (M-H, Random, 95% CI)0.23 [0.06, 0.84]

    1.3 versus Nortriptyline
135Odds Ratio (M-H, Random, 95% CI)0.65 [0.16, 2.68]

 2 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

    2.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 3 Citalopram versus other SSRIs2694Odds Ratio (M-H, Random, 95% CI)0.62 [0.24, 1.63]

    3.1 Versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

    3.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.53 [0.19, 1.47]

 4 Citalopram versus other conventional ADs1357Odds Ratio (M-H, Random, 95% CI)0.25 [0.03, 2.28]

    4.1 versus Reboxetine
1357Odds Ratio (M-H, Random, 95% CI)0.25 [0.03, 2.28]

 
Comparison 87. SE - Weight gain

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus other SSRIs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Versus Escitalopram
2651Odds Ratio (M-H, Random, 95% CI)1.21 [0.55, 2.64]

    1.2 Versus Sertraline
1400Odds Ratio (M-H, Random, 95% CI)0.85 [0.48, 1.49]

 2 Citalopram versus other conventional ADs3Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Mirtazapine
1270Odds Ratio (M-H, Random, 95% CI)0.26 [0.10, 0.67]

    2.2 versus Reboxetine
2458Odds Ratio (M-H, Random, 95% CI)2.37 [0.61, 9.19]

 
Comparison 88. SE - Yawning

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Citalopram versus heterocyclics196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

    1.1 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 
Comparison 89. Deaths, suicide and suicidality

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 DSH6Odds Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 versus Amitriptyline
151Odds Ratio (M-H, Random, 95% CI)2.77 [0.11, 71.35]

    1.2 versus Escitalopram
1248Odds Ratio (M-H, Random, 95% CI)0.2 [0.01, 4.21]

    1.3 versus Fluoxetine
2673Odds Ratio (M-H, Random, 95% CI)1.03 [0.33, 3.23]

    1.4 versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)0.20 [0.01, 4.18]

    1.5 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)1.21 [0.14, 10.51]

 2 Suicide - Tendency/Ideation1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    2.1 versus Escitalopram
1248Odds Ratio (M-H, Random, 95% CI)0.34 [0.01, 8.33]

 3 Suicide - completed41079Odds Ratio (M-H, Random, 95% CI)1.37 [0.29, 6.42]

    3.1 versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

    3.2 versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 75.85]

    3.3 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)0.24 [0.01, 3.88]

    3.4 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 4 Deaths (any cause)4Odds Ratio (M-H, Random, 95% CI)Subtotals only

    4.1 versus Escitalopram
1294Odds Ratio (M-H, Random, 95% CI)2.82 [0.11, 69.84]

    4.2 versus Fluvoxamine
1217Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 75.85]

    4.3 versus Imipramine
1472Odds Ratio (M-H, Random, 95% CI)1.22 [0.06, 25.67]

    4.4 versus Maprotiline
196Odds Ratio (M-H, Random, 95% CI)3.06 [0.12, 77.09]

 
Table 1. Adverse events

Adverse eventStudyCItalopramComparatorOdds Ratio, Random [95% CI]


EventsTotalEventsTotal

Citalopram versus TCAs

Citalopram vs amitriptyline

AstheniaShaw 19863275250.50 [0.11, 2.35]

ConfusionShaw 19862275250.32 [0.06, 1.83]

ConjunctivitisGravem 19871270242.77 [0.11, 71.35]

Dermatological problemsGravem 19871271240.88 [0.05, 14.96]

DizzinessGravem 1987; Kyle 1998; Shaw 198616233282350.47 [0.15, 1.44]

FatigueKyle 19986179111860.55 [0.20, 1.53]

GastrointestinalGravem 1987; Shaw 19863546490.45 [0.10, 2.07]

HeadacheGravem 1987; Hosak 1999; Kyle 1998; Shaw 198622262182661.25 [0.65, 2.42]

Loss of hairGravem 19871270242.77 [0.11, 71.35]

MeteorismGravem 19870271240.28 [0.01, 7.33]

PalpitationsGravem 1987; Shaw 19864549490.36 [0.10, 1.24]

RashShaw 19861271250.92 [0.05, 15.59]

RestlessnessGravem 1987; Shaw 19864545490.71 [0.18, 2.82]

SweatingGravem 19872273240.56 [0.09, 3.67]

SyncopeGravem 19870271240.28 [0.01, 7.33]

Taste abnormalitiesGravem 19870271240.28 [0.01, 7.33]

TremorGravem 19871271240.88 [0.05, 14.96]

Visual problemsGravem 19870273240.11 [0.01, 2.28]

Citalopram vs imipramine

AstheniaLu 10-171, 83-012223210.60 [0.09, 4.01]

DizzinessLu 10-171, 83-0172212210.35 [0.10, 1.22]

GastrointestinalLu 10-171, 83-016225211.20 [0.30, 4.74]

HeadacheLu 10-171, 83-016222213.56 [0.63, 20.15]

IrritabilityRosenberg 19942838012920.53 [0.26, 1.09]

RestlessnessLu 10-171, 83-013224210.67 [0.13, 3.44]

Citalopram vs maprotiline

Appetite increasedBouchard 19871481481.00 [0.06, 16.46]

Concentration decreaseBouchard 19871480483.06 [0.12, 77.09]

Craving for sweetsBouchard 19872480485.22 [0.24, 111.55]

Dermatological problemsBouchard 19871481481.00 [0.06, 16.46]

DizzinessBouchard 19877485481.47 [0.43, 5.00]

DyspepsiaBouchard 19872481482.04 [0.18, 23.32]

DyspneaBouchard 19870481480.33 [0.01, 8.22]

Feeling of numbnessBouchard 19872480485.22 [0.24, 111.55]

HeadacheBouchard 19876483482.14 [0.50, 9.12]

HypertoniaBouchard 19871481481.00 [0.06, 16.46]

Increased salivationBouchard 19871480483.06 [0.12, 77.09]

Nasal congestionBouchard 19871481481.00 [0.06, 16.46]

Orthostatic symptomsBouchard 19873483481.00 [0.19, 5.22]

RestlessnessBouchard 19871485480.18 [0.02, 1.63]

SweatingBouchard 19878484482.20 [0.62, 7.87]

TachycardiaBouchard 19873485480.57 [0.13, 2.55]

Taste abnormalitiesBouchard 19871480483.06 [0.12, 77.09]

TremorBouchard 19875488480.58 [0.18, 1.93]

Visual problemsBouchard 19871480483.06 [0.12, 77.09]

YawningBouchard 19871480483.06 [0.12, 77.09]

Citalopram vs nortriptyline

ConfusionLu 10-171,79-011170183.36 [0.13, 88.39]

HeadacheLu 10-171,79-015175181.08 [0.25, 4.70]

PalpitationsLu 10-171,79-014174181.08 [0.22, 5.22]

PruritusLu 10-171,79-015173182.08 [0.41, 10.53]

Citalopram versus heterocyclics

Citalopram vs mianserin

Back painKarlsson 20006163101730.62 [0.22, 1.75]

DizzinessKarlsson 20004163101730.41 [0.13, 1.33]

HeadacheKarlsson 200012163121731.07 [0.46, 2.45]

Pain (general)Karlsson 2000616391730.70 [0.24, 2.00]

Citalopram versus other SSRIs

Citalopram vs escitalopram

Abdominal painMoore 2005115201422.82 [0.11, 69.84]

Accidental injuryColonna 20054182101750.37 [0.11, 1.21]

Aggressive behaviourMoore 2005015211420.31 [0.01, 7.65]

AnorexiaOu 2010; Yevtushenko 2007222542230.64 [0.06, 7.29]

AstheniaMoore 2005215221420.93 [0.13, 6.72]

Back painColonna 2005; SCT-MD-0214305123001.36 [0.34, 5.51]

Breast surgeryMoore 2005115201422.82 [0.11, 69.84]

BronchitisColonna 20053182101750.28 [0.07, 1.02]

Chest painMoore 2005115201422.82 [0.11, 69.84]

Chicken poxMoore 2005015211420.31 [0.01, 7.65]

Dermatological problemsYevtushenko 2007211011092.00 [0.18, 22.38]

DizzinessMoore 2005; Ou 2010; SCT-MD-02; Yevtushenko 200711502174910.69 [0.28, 1.71]

DyspepsiaYevtushenko 2007111001093.00 [0.12, 74.45]

EnuresisMoore 2005015211420.31 [0.01, 7.65]

Exacerbation of depressionMoore 2005115201422.82 [0.11, 69.84]

GastrointestinalOu 201014117161150.84 [0.39, 1.81]

HeadacheColonna 2005; Moore 2005; SCT-MD-02; Yevtushenko 200745567465510.96 [0.49, 1.88]

Hot flashMoore 2005015211420.31 [0.01, 7.65]

Memory impairmentMoore 2005215201424.73 [0.23, 99.47]

PalpitationsMoore 2005015211420.31 [0.01, 7.65]

Panic attackMoore 2005115201422.82 [0.11, 69.84]

PharyngitisMoore 2005015211420.31 [0.01, 7.65]

PruritusMoore 2005115201422.82 [0.11, 69.84]

RashYevtushenko 2007111001093.00 [0.12, 74.45]

RhinitisColonna 2005; Lepola 2003; SCT-MD-0224466284560.87 [0.40, 1.87]

Sexual problems: erectile dysfunctionLepola 2003016121560.19 [0.01, 4.02]

Sexual problems: increased sexual desireSCT-MD-02912381251.15 [0.43, 3.10]

Sexual problems: otherBurke 2002; Moore 2005; SCT-MD-02; Yevtushenko 200716452315630.72 [0.36, 1.43]

SweatingLepola 2003; Moore 2005; SCT-MD-0213436154230.83 [0.39, 1.78]

TachycardiaSCT-MD-02012311250.34 [0.01, 8.33]

TremorMoore 2005015241420.10 [0.01, 1.89]

Upper respiratory tract infectionSCT-MD-028123121250.66 [0.26, 1.66]

Visual problemsMoore 2005115201422.82 [0.11, 69.84]

Weight gainColonna 2005; Moore 200515334123171.21 [0.55, 2.64]

Citalopram vs fluoxetine

Abdominal painBougerol 1997a; Bougerol 1997b16331103421.57 [0.55, 4.53]

Back painBougerol 1997b5173018412.04 [0.66, 219.46]

BronchitisBougerol 1997b517371840.75 [0.23, 2.42]

Decreased weightBougerol 1997a; Bougerol 1997b13331223420.62 [0.25, 1.50]

HeadacheBougerol 1997a; Bougerol 1997b; Hosak 199925360283720.90 [0.51, 1.60]

Influenza-like symptomsBougerol 1997b217361840.35 [0.07, 1.74]

NervousnessBougerol 1997a615851581.21 [0.36, 4.04]

PruritusBougerol 1997a215851580.39 [0.07, 2.05]

SweatingBougerol 1997a615821583.08 [0.61, 15.49]

TensionBougerol 1997a615861581.00 [0.32, 3.17]

VertigoBougerol 1997a715831582.40 [0.61, 9.43]

Citalopram vs paroxetine

Asthenia29060/78536207221991.69 [0.96, 3.00]

Headache29060/78554207441991