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Strategies for managing sexual dysfunction induced by antidepressant medication

  1. Matthew J Taylor1,*,
  2. Lisa Rudkin2,
  3. Philippa Bullemor-Day1,
  4. Jade Lubin3,
  5. Christopher Chukwujekwu4,
  6. Keith Hawton5

Editorial Group: Cochrane Common Mental Disorders Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 1 JAN 2013

DOI: 10.1002/14651858.CD003382.pub3


How to Cite

Taylor MJ, Rudkin L, Bullemor-Day P, Lubin J, Chukwujekwu C, Hawton K. Strategies for managing sexual dysfunction induced by antidepressant medication. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD003382. DOI: 10.1002/14651858.CD003382.pub3.

Author Information

  1. 1

    Institute of Psychiatry, King's College London, Department of Psychosis Studies, London, UK

  2. 2

    Bradford Community NHS Trust, Assertive Outreach, Bradford, UK

  3. 3

    Institute of Psychiatry, Department of Psychosis Studies, London, UK

  4. 4

    Coventry and Warwickshire NHS partnership trust, Old Age Psychiatry, Rugby, UK

  5. 5

    Warneford Hospital, Centre for Suicide Research, University Department of Psychiatry, Oxford, UK

*Matthew J Taylor, Department of Psychosis Studies, Institute of Psychiatry, King's College London, De Crespigny Park, London, SE5 8AF, UK. matthew.j.taylor@kcl.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 31 MAY 2013

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Characteristics of included studies [ordered by study ID]
Baldwin 2008

MethodsDouble-blind, multicentreD (37 sites), parallel group, 4-week duration


Participants288 adults (ages 22-67 years) randomised (84 men, 204 women).

Inclusion criteria: sexually active at least once a week; sexual dysfunction treatment-emergent; ASEX score 19 or more; stable dosage of fluoxetine or paroxetine for at least 8 weeks prior to screening and for 3 months.

Exclusion criteria: HAM-D score of 12 or more


Interventions1. VML-670 (300 μg once daily) or,

2. Placebo daily


OutcomesAssessed with following scales: ASEX, CGI, HAM-D


Notes37 UK primary care sites

VML-670 is a 5-HT1A receptor agonist


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated schedule

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low riskAll study personnel and participants were blinded to treatment assignment for duration of the study

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAll study personnel and participants were blinded to treatment assignment for duration of the study

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAll study personnel and participants were blinded to treatment assignment for duration of the study

Incomplete outcome data (attrition bias)
All outcomes
Low risk-

Selective reporting (reporting bias)Unclear risk-

Bernik 2004

MethodsDouble-blind, 2 period cross-over design, 2 weeks of active treatment


Participants12 men (aged 18-65 years) randomised

Inclusion criteria: In remission from panic disorder; treated with clomipramine; ejaculatory delay or anorgasmia (no participants with erectile dysfunction)


Interventions1. Bethanecol chloride 20 mg as needed (taken 45 minutes before sexual intercourse on up to 2 occasions in each 2-week period), or

2. Placebo


OutcomesChanges in VAS sexual function scale


NotesTrial performed in Brazil

Bethanecol has mixed central and peripheral cholinergic and adrenergic effects


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Clayton 2004

MethodsDouble-blind, parallel-arm, multicentred (3 sites), 4-weeks duration


Participants55 adults (aged 18-45 years) randomised (48 women, 7 men).
Includsion criteria: DSM-IV depression with sustained remission; developed or worsened sexual problems on current SSRI treatment


Interventions1. Bupropion SR 150 mg (once daily for 3 days, increasing to twice daily if tolerated) in addition to SSRI, or

2. Placebo twice daily, in addition to SSRI


OutcomesCSFQ, HAM-D


NotesUSA sites

Bupropion is thought to act by dual inhibition of norepinephrine and dopamine reuptake


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Unclear risk-

DeBattista 2005

MethodsDouble-blind, parallel-arm trial, 6-week duration


Participants41 adults (aged 18-60 years) randomised (17 men, 24 women).

Inclusion criteria: stable dose of fluoxetine, paroxetine, citalopram or sertraline for at least 6 weeks; sexual side effects which participants believed were temporally related to the antidepressant use; ASEX score of at least 15


Interventions1. Bupropion SR 150 mg once daily for six weeks, in addition to current SSRI, or

2. Placebo for six weeks, in addition to current SSRI


OutcomesASEX, HAM-D, Beck Depression Inventory


NotesTrial performed in USA

Bupropion is thought to act by dual inhibition of norepinephrine and dopamine reuptake


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)High riskNo outcome data reported for secondary measures

Dording 2008

MethodsParallel group trial, 12 weeks of treatment


Participants20 adults (3 men, 17 women)

Inclusion criteria: depression in remission (HAM-D < 10); SSRI-induced sexual dysfunction for at least 4 weeks (no sexual dysfunction before antidepressant, clear temporal relationship between antidepressant and dysfunction)


Interventions1. Maca root (Lepidium meyenii) extract 3.0 g/day, or

2. Maca root (L meyenii) extract 1.5 g/day


OutcomesASEX, MGH-SFQ, HAM-D, HAM-A


NotesTrial performed in USA

Maca, also known as “Peruvian Ginseng,” is a plant traditionally used for medicinal purposes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear risk-

Evliyaoğlu 2011

MethodsParallel group trial, 12-week duration


Participants54 men (aged 23-74 years) randomised.

Inclusion criteria: sexual dysfunction emerged during antidepressant (SRI) treatment; dysfunction continued for 4 weeks or more


Interventions1. Tadalafil 20 mg, or

2. Placebo

Tadalafil or placebo taken 1 h before sexual activity, and not more than once daily


OutcomesIIEF; SEP diary; Global Assessment Questions


NotesTrial performed in Turkey

Tadalafil is a phosphodiesterase type 5 inhibitor


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskStates 'randomly assigned', but no details provided on method of sequence generation

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Participants, physicians and data collators were unaware of the treatment assignment of the patients'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Participants, physicians and data collators were unaware of the treatment assignment of the patients'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Participants, physicians and data collators were unaware of the treatment assignment of the patients'

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data

Selective reporting (reporting bias)Low riskAll outcomes described

Fava 2006

MethodsDouble-blind, parallel-arm trial, 6-week duration


Participants142 men (aged 27-74 years) randomised.

Inclusion criteria: SSRI-associated erectile dysfunction (Sexual Health Inventory for Men score > 20); no erectile dysfunction prior to antidepressant; DSM-IV major depressive disorder currently in remission (HAM-D < 10); taking SRI for 8 weeks or more, and stable dose for 4 weeks


Interventions1. Sildenafil 50 mg daily initially then variable dose later (25-100 mg depending on efficacy and tolerability), or

2. Placebo


OutcomesIIEF, Erectile Dysfunction Inventory of Treatment Satifisaction, Global Efficacy Questionnaire, HAM-D, Beck Anxiety Inventory


NotesCentres in USA, Germany, UK, Canada

Sildenafil is a phosphodiesterase inhibitor


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomly assigned using a computer algorithm of random permuted blocks

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear risk-

Ferguson 2001

MethodsDouble-blind, parallel-arm, multicentreD (9 sites) trial, 10-week duration


Participants75 adults (aged 18-65 years) randomised (34 women, 38 men).
Inclusion criteria: DSM-III-R moderate or severe depressive episode; sexual dysfunction due to sertraline; judged clinically stable and able to discontinue sertraline; all symptoms of sexual dysfunction absent during placebo run-in phase


Interventions1-week washout period when sertraline treatment suspended, then 7-10 day placebo lead in, then:

1. Nefazodone 100 mg twice daily increasing to 200 mg after 1 week, or

2. Sertraline 50 mg once daily increasing to 100 mg after 1 week and placebo at night


OutcomesPhysician's rating of sexual dysfunction, modified version of Rush-Presbyterian Sexual Function Inventory, HAM-D, CGI (for depressive symptoms)


NotesTrial performed in USA, 9 sites


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details of sequence generation method provided

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskThree of 75 participants randomised excluded from efficacy analyses

Selective reporting (reporting bias)Unclear risk-

Ginsberg 2001

MethodsDouble-blind, parallel-arm trial, 8-week duration


Participants23 men (aged 30-64 years).

Inclusion criteria: clinically recovered mood or anxiety disorder; SSRI associated sexual dysfunction (SSRI or venlafaxine); medications stable for 4 weeks prior and during study


Interventions1. Sildenafil 50-100 mg once daily for 8 weeks, or

2. Placebo for 8 weeks


OutcomesIIEF, ASEX, Erectile Dysfunction Inventory of Treatment Satifsaction, Rigiscan


NotesMulticentred

Sildenafil is a phosphodiesterase inhibitor


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)High riskNot all outcomes reported (abstract, not full publication)

Jacobsen 1996

MethodsCross-over design, 2 sequential 3-week trials


Participants33 participants (11 men, 22 women).

Inclusion criteria: sexual dysfunction after starting SRI treatment; DSM-IV major depression, bipolar disorder, or obsessive compulsive disorder; fluoxetine or sertraline taken for at least 8 weeks prior to study entry


Interventions1. Yohimbine 5.4 mg three times daily, or

2. Placebo three times daily


Outcomes4-point scales for libido, orgasm, erection (men), mood, anxiety, sleep disturbance, gastrointestinal distress, flushing


NotesTrial performed in USA

Yohimbine blocks alpha-2 adrenoceptors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear whether more than 33 people randomised

Selective reporting (reporting bias)Unclear risk-

Jespersen 2004

MethodsDouble-blind, parallel-arm trial, 14-day duration


Participants12 women (age range unclear) randomised.

Inclusion criteria: antidepressant-induced sexual dysfunction; past diagnosis of depression (by MINI neuropsychiatric interview); no change in psychotropic treatment in previous 2 months; no comorbid psychiatric or medical disorder; no past history of sexual dysfunction


Interventions1. Granisetron (dose not specified), or

2. Placebo


OutcomesFSFSQ, ASEX, CGI ratings of depressive symptoms


NotesTrial performed in South Africa.

Granisetron is a 5-HT3 antagonist


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details of random sequence generation provided

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear risk-

Kang 2002

MethodsDouble-blind, parallel-arm, single-centre trial, 2-month duration


Participants37 adults randomised (27 men, 10 women).
Inclusion criteria: DSM-IV substance-induced sexual dysfunction; antidepressant treatment of depressive disorder (without psychotic features) or anxiety disorder; regular sexual activity


Interventions1. Ginkgo biloba (EGb761) 120 mg/day increasing to 160 mg/ day after 2 weeks, and increasing to 240 mg/day after 4 weeks, or

2. Placebo


OutcomesInvestigator-developed questionnaire, Beck Depression Inventory (Korean version), State-Trait Anxiety Inventory


NotesTrial performed in South Korea


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk'Random number table'

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear risk-

Masand 2001

MethodsDouble-blind, parallel-arm trial, 3-week duration


Participants31 adults randomised (breakdown by gender unknown).
Inclusion criteria: receiving SSRI for at least 6 weeks; sexual dysfunction attributed to SSRI (ASEX score: total score of 19 or more on the ASEX scale or any individual item score > 5 or any 3 items equal to 4); HAM-D score < 10


Interventions1. Bupropion SR 150 mg daily, or

2. Placebo


OutcomesASEX, HAM-D, UKU side effects rating scale


NotesTrial performed in the USA


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear risk-

Meston 2004

MethodsDouble-blind, cross-over design, 8-week duration


Participants29 women randomised.

Inclusion criteria: SSRI for depression; at least 10 weeks treatment; treatment otherwise successful;

sexual dysfunction onset not less than 1 week and not more than 3 months after beginning SSRI; sexual dysfunction distinctly different from any noticed during depressed phase


Interventions1. Ephedrine 50 mg once daily, or

2. Placebo

Treatments to be taken approximately 1 h before sexual activity


OutcomesBISF-W, Beck Depression Inventory


NotesTrial performed in USA


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information on sequence generation method provided

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Low risk-

Selective reporting (reporting bias)Unclear risk-

Michelson 2000

MethodsDouble-blind, parallel-arm, multicentred trial (3 sites), 8 weeks of treatment


Participants61 women (aged 50 years or younger) randomised.
Inclusion criteria: stable dose of fluoxetine for at least 8 weeks; impaired orgasm or sexual arousal or vaginal lubrication with onset after initiation of fluoxetine; CGI sexual function score of at least 3, HAM-D score < 11


Interventions1. Buspirone 10 mg twice daily increasing to 15 mg in addition to fluoxetine, or

2. Amantadine 50 mg once daily increasing to 50 mg twice daily in addition to fluoxetine, or

3. Placebo twice daily, in addition to fluoxetine


OutcomesInterviewer Rating of Sexual Function,

Participant-rated VAS for sexual function,

Clinician-rated global impression and participant-rated global impression,

HAM-D, Beck Depression Inventory, State-Trait Anxiety Inventory


NotesTrial performed in USA.

Buspirone is a 5HT-1A agonist

Amantadine is thought to increase dopamine availability


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details of sequence generation method provided

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Patients and efficacy raters were blinded to treatment assignment and to the criteria for study entry and dose adjustments'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Patients and efficacy raters were blinded to treatment assignment and to the criteria for study entry and dose adjustments'

Blinding of outcome assessment (detection bias)
All outcomes
Low riskPatients and efficacy raters were blinded to treatment assignment and to the criteria for study entry and dose adjustments

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskData analysed from 57 out of total of 61 randomised

Selective reporting (reporting bias)Unclear risk-

Michelson 2002

MethodsDouble-blind, parallel-arm. multicentred trial (12 centres), 6-week treatment period


Participants148 women randomised.
Inclusion criteria: stable dose of fluoxetine leading to reduced lubrication, or orgasmic dysfunction, or both; condition for which fluoxetine prescribed responded satisfactorily


Interventions1. Mirtazapine 15 mg once daily increasing to 30 mg in addition to fluoxetine, or

2. Yohimbine 5.4 mg once daily increasing to 10.8 mg in addition to fluoxetine, or

3. Olanzapine 2.5 mg once daily increasing to 5 mg in addition to fluoxetine, or

4. Placebo, in addition to fluoxetine.

Medications taken daily 1-2 h before sexual activity


OutcomesParticipant-assessment of sexual function, Daily diary VAS, Kinsey Ratings of Sexual Function - computer-assisted structured interview


NotesTrial performed in USA.

Mirtazapine is a 5HT2 and alpha-2 adrenergic antagonist.

Yohimbine is an alpha-2 adrenergic antagonist.

Olanzapine is a 5HT2 antagonist (and dopamine antagonist)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo data on sequence generation method provided

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Nelson 2001

MethodsDouble-blind, cross-over design, 6-week duration


Participants20 adults randomised (2 men, 18 women).
Inclusion criteria: sexual dysfunction began whilst taking SSRI; HAM-D score < 10


Interventions1. Granisetron 1-2 mg, as required, in addition to SSRI, or

2. Placebo, in addition to SSRI.

Medication taken 1-2 h prior to sexual activity


OutcomesSSES, HAM-D


NotesTrial performed in USA.

Granisetron is a 5-HT3 antagonist


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details of sequence generation method provided

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low risk'Double blind'

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Nurnberg 2008

MethodsDouble-blind, randomised, placebo-controlled, multicentred trial, 8-week duration


Participants98 women randomised, aged 18-50 years.

Includsion criteria: substance-induced sexual dysfunction to DSM-IV criteria; major depressive disorder, in remission; taking antidepressant with serotonin reuptake inhibition action for at least 8 weeks; persistent sexual dysfunction for at least 4 weeks


Interventions1. Sildenafil, flexible dose between 50 mg and 100mg, or

2. Placebo

Medication taken 1-2 h before sexual activity, not more than once daily


OutcomesCGI scale, Sexual Function Questionnaire, ASEX, University of New Mexico Sexual Function Inventory - female version


NotesTrial performed in USA - 7 centres


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskUsed an unrestricted computer-generated randomisation schedule using SPSS version 10, restriction to this randomisation was that the groups had to be of equal size

Allocation concealment (selection bias)Low riskThe randomisation schedule was given to an independent pharmacy.

Medications were sealed in sequentially-numbered identical containers according to allocation sequence

Blinding (performance bias and detection bias)
All outcomes
Low riskAll study personnel and participants were blinded to treatment assignment for the duration of the study

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAll study personnel and participants were blinded to treatment assignment for the duration of the study

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAll study personnel and participants were blinded to treatment assignment for the duration of the study

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Nurnberg 2002

MethodsMulticentred, double-blind, placebo-controlled trial, 8-week duration, followed by single-blind, open-label 8-week extension


Participants150 women.

Inclusion criteria: major depressive disorder in remission; serotonergic reuptake inhibitor-associated female sexual dysfunction; no pre-existing sexual dysfunction; 38 weeks stable dose SRI; HAM-D score < 10; significant sexual dysfunction by CGI-SF


Interventions1. Sildenafil (50-100 mg flexible dose), or

2. Matching placebo


OutcomesCGI-SF, HAM-D


NotesLimited information, no outcome data available from end of randomised phase.

Outcomes reported after further open-label sildenafil treatment


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk-

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Unclear risk-

Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk-

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk-

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Nurnberg 2003

MethodsMulticentred (3 centres), double-blind, parallel-arm trial, 6-week duration


Participants90 men (aged 18-55 years) randomised.
Inclusion criteria: taking stable dose of an SSRI with substance-induced sexual dysfunction for more than 4 weeks; DSM-IV major depressive disorder in remission; HAM-A score < 11; HAM-D score < 11.


Interventions1. Sildenafil 50 mg, as required, increasing to 100 mg, as required, in addition to SSRI, or

2. Placebo in addition to SSRI


OutcomesIIEF, ASEX, MGH-SFQ, HAM-D


NotesTrial performed in USA - 3 centres


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskDeveloped an unrestricted computer-generated randomisation schedule using SPSS version 10

Allocation concealment (selection bias)Low riskRandomisation schedule was given to an independent pharmacy. Medications were sealed in sequentially-numbered, identical containers according to allocation sequence

Blinding (performance bias and detection bias)
All outcomes
Low riskAll study personnel and patents were blinded to treatment for the duration of the study

Blinding of participants and personnel (performance bias)
All outcomes
Low riskAll study personnel and patents were blinded to treatment for the duration of the study

Blinding of outcome assessment (detection bias)
All outcomes
Low riskAll study personnel and patents were blinded to treatment for the duration of the study

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Safarinejad 2010

MethodsParallel-group design, 12-week randomised phase


Participants234 men (aged 25-50 years).

Inclusion criteria: major depressive disorder currently in remission; stable dose of SSRI for at least 6 months; new sexual dysfunction for at least 4 weeks


Interventions1. Bupropion SR 150 mg twice daily, or

2. Placebo


OutcomesCGI-SF, IIEF, ASEX, Erectile Dysfunction Inventory of Treatment Satisfaction (patient and partner versions), HAM-D and HAM-A


NotesTrial performed in Iran


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomisation number for assignment to treatment group was determined using random permuted blocks

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low risk'Double blind'

Blinding of participants and personnel (performance bias)
All outcomes
Low risk'Double blind'

Blinding of outcome assessment (detection bias)
All outcomes
Low riskInvestigator was not involved in the recruitment procedure and did not know the randomisation list. Seals were broken after the trial

Incomplete outcome data (attrition bias)
All outcomes
Low risk

Selective reporting (reporting bias)Unclear risk-

Safarinejad 2011

MethodsParallel-group design, 12 weeks of randomised treatment after 1 week placebo run-in


Participants218 women (aged 25-45).

Inclusion criteria: SSRI-induced sexual dysfunction; first episode of major depressive disorder in remission


Interventions1. Bupropion SR 150 mg twice daily, or

2. Placebo


OutcomesCGI-SF, Female Sexual Function Index, HAM-D


NotesTrial performed in Iran


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated schedule

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blind

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk-

Selective reporting (reporting bias)Unclear risk-

Wheatley 2004

MethodsTriple-blind, parallel-arm design. 12 weeks of treatment after 1 week run-in without treatment


Participants24 adults randomised (14 men, 10 women), aged 18-65 years.

Inclusion criteria: taking antidepressant for at least 2 weeks and experiencing sexual problems as a consequence


Interventions1. Ginkgo biloba (LI-156) 240 mg daily, or

2. Placebo daily


OutcomesChanges in sexual dysfunction scale, ASEX, University of Mexico Sexual Function Inventory


NotesTrial performed in the UK


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated schedule

Allocation concealment (selection bias)Unclear risk-

Blinding (performance bias and detection bias)
All outcomes
Unclear riskAllocation blinded to participant, investigator and statistician

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskAllocation blinded to participant, investigator and statistician

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk-

Incomplete outcome data (attrition bias)
All outcomes
Low risk-

Selective reporting (reporting bias)Unclear risk-

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aizenberg 2003Non-randomised design

Amiaz 2011Not established as antidepressant-induced sexual dysfunction: depressed men, also hypogonadal (low or low-normal testosterone levels)

Ashton 1998Non-randomised design

Berk 2000Non-randomised design

Cohen 1999Non-randomised design

Dording 2012Not established as antidepressant-induced sexual dysfunction: changes in sexual dysfunction ratings during treatment for resistant depression

Gelenberg 2000Non-randomised design

Landen 1999Not established as antidepressant-induced sexual dysfunction: changes in sexual dysfunction ratings during treatment for resistant depression

Mansoori 2011Not a study of sexual dysfunction effects (safety evaluation)

Moore 2002Review article

Nurnberg 2001Pooled analysis of subgroup data from multiple individual studies; participants taking antidepressant medication, but not established as antidepressant-induced sexual dysfunction

Ozmenler 2008Non-randomised design

Pae 2009Not established as antidepressant-induced sexual dysfunction: changes in sexual dysfunction ratings during treatment for resistant depression

Salerian 2000Non-randomised design

Salerian 2002Non-randomised design

Segraves 2007Pooled analysis of subgroup data from multiple individual studies; participants taking antidepressant medication, but not established as antidepressant-induced sexual dysfunction

Tignol 2004Not established as antidepressant-induced sexual dysfunction: persistent erectile dysfunction after depression was brought into remission with or without antidepressant medication

Walker 1993Non-randomised design

Worthington 2002Non-randomised design

 
Characteristics of studies awaiting assessment [ordered by study ID]
Croft 2012

MethodsRandomized allocation

ParticipantsWomen, aged 18-50 years.

Inclusion criteria: mild or remitted depressive disorder; SSRI or SNRI; decreased sexual desire and distress present for at least 4 weeks

Interventions1. Flibanserin, or

2. Placebo

Outcomes

Notes

Kashani 2013

MethodsRandom allocation

Participants38 women.

Inclusion criteria: major depression; stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks; had experienced subjective feeling of sexual dysfunction

Interventions1. Saffron (30 mg/daily), for 4 weeks, or

2. Placebo for 4 weeks

OutcomesFSFI

Notes

MGH 2013

MethodsRandomised allocation

ParticipantsWomen, aged 45-65 years.

Inclusion criteria: post-menopause; persistent depression despite SSRI treatment

Interventions1. Testosterone cream, or

2. Placebo

Outcomes

NotesStudy title 'Testosterone Antidepressant Augmentation in Women'

Modabbernia 2012

MethodsRandomised, double-blind, placebo-controlled study

Participants36 men

Inclusion criteria: major depressive disorder; depressive symptoms stabilized on fluoxetine; subjective complaints of sexual impairment

Interventions1. Saffron (15 mg twice per day) for 4 weeks, or

2. Placebo for 4 weeks

OutcomesIIEF scale

Notes

 
Characteristics of ongoing studies [ordered by study ID]
Chiang 2010

Trial name or titleTrazodone for SSRI-SD in Civilian Administration Division of Beitou Armed Forces Hospital

MethodsRandomized, placebo-control. cross-over design, 6-week duration

ParticipantsInclusion criteria: participants 20-65 years of age; receiving SSRI treatment for > 4 weeks; minimal dose of fluoxetine, paroxetine, and citalopram 20 mg/day; minimal dose of fluvoxamine and sertraline 50 mg/day; and minimal dose of escitalopram 10 mg/day; developing sexual dysfunction based on the definition of ASEX Chinese version

Interventions1. Trazodone 50 mg/day titrated to 100 mg/day over 1 week, then maintained, or

2. Placebo

OutcomesPrimary outcomes: differences between trazodone and placebo in the ASEX Chinese version at the end of week 6.

Secondary outcomes assessed include: difference between trazodone and placebo in the CGI scale, 10-point VAS, HAM-D, and HAM-A at the end of week 6. Relationships between 5-HT2A polymorphism and changes in ASEX Chinese version also evaluated.

Starting date2010

Contact informationKuo-Tung Chiang, MD

Notes

Dording 2010

Trial name or titleA double-blind, placebo-controlled study of maca root for the treatment of antidepressant-induced sexual dysfunction in women

MethodsRandomized. 12-week duration

ParticipantsWomen, 18-80 years

Interventions1. Maca root 3 g/day, or

2. Placebo

OutcomesDecrease in baseline ASEX and MGH-Sexual Dysfunction scores

Starting date2007

Contact informationChristina Dording, MD, Massachussetts General Hospital

Notes

Hellerstein 2008

Trial name or titleTreatment of sexual dysfunction secondary to antidepressant pharmacotherapy: a double-blind comparison of Requip (Ropinirole) vs placebo in patients taking SSRI antidepressants

MethodsRandomized, cross-over trial, 6- week duration

ParticipantsInclusion criteria: male or female outpatients, 18-65 years old; currently taking fluoxetine, sertraline, paroxetine, citalopram, or escitalopram at a stable dosage within the ranges specified for 1 month or longer; required dosage range: (Prozac (fluoxetine) 20-80 mg/day; Celexa (citalopram) 20-60 mg/day; Lexapro (escitalopram) 10-30 mg/day; Zoloft (sertraline) 50-200 mg/day; Paxil (paroxetine) 20-60 mg/day; Paxil CR (paroxetine CR) 25-75 mg/day; currently responding to SSRI antidepressant treatment, as indicated by a score of 15 or less on the HAM-D 24-item at screening and baseline, and (b) CGI-Severity score of 2 or less at baseline; meets DSM-IV criteria for Substance-Induced Sexual Dysfunction, with impairment of desire, arousal, or orgasm; currently involved in an intimate relationship that includes sexual contact; agree to use double-barrier contraception during sexual intercourse during the course of the study (women only); agree to let the study team contact the physician who prescribed the SSRI medication to inform him/her of patient's participation in the current study

Interventions1. Ropinirole 1 mg extended release formulation given once/day to a maximum of 4/day

2. placebo

OutcomesPrimary outcomes: IIEF, SFSQ
Secondary outcomes: HAM-D 17-items, GAFS, CGI, CGI-SF

Starting date2006

Contact informationDavid J Hellerstein, MD St. Luke's Roosevelt Hospital Center and NY State Psychiatric Institute

Notes

Meston 2008

Trial name or titleGinkgo Biloba: Antidepressant-Induced Sexual Dysfunction

MethodsParallel-group design

Participants36 women (age 18-65 years).

Inclusion criteria: stabilised on antidepressant medication and free of a current Axis I disorder

Interventions1. Ginkgo biloba extract 200 mg for 8 weeks, or

2. Placebo for 8 weeks

OutcomesDaily participant diary, participant-rating scales, blind independent evaluator ratings, vaginal photoplethysmography

Starting dateJune 2002

Contact informationCindy Meston, University of Texas at Austin

NotesOutcomes for those with antidepressant-associated sexual dysfunction not yet published

Takeda 2011

Trial name or titleA randomised, double-blind, parallel-group, active-controlled, flexible-dose study evaluating the effect of Lu AA21004 vs escitalopram on sexual functioning in adults with well-treated major depressive disorder experiencing selective serotonin reuptake inhibitor-induced sexual dysfunction

MethodsRandomised; parallel-group design; blinding applied to subjects, caregivers, investigators, outcomes assessors, 8-week treatment duration

ParticipantsEstimated enrolment: 440, aged 18-55 years; male and female participants.

Inclusion criteria: treated for last 8 weeks, or more, with SSRI monotherapy (only citalopram, paroxetine, or sertraline allowed) prescribed to treat a major depressive episode, according to the DSM-IV-TR criteria; depression currently stable; subject has a CGI Scale-Severity of Illness Scale (CGI-S) score of ≤ 3; currently experiencing treatment-emergent sexual dysfunction (defined as a CSFQ-14 total score ≤ 41 for women and ≤ 47 for men); considered to be attributable to the current SSRI monotherapy; suitable for a switch in medication

Interventions1. Lu AA21004 up to 20 mg daily, or

2. Escitalopram up to 20 mg daily

OutcomesPrimary outcome: change from baseline in the CSFQ-14 Total Score

Starting dateJune 2011

Contact informationContact: Takeda Study Registration Call Center

Notes62 study locations in USA and Canada

Lu AA21004 is also known as vortioxetine

Van Rooiji 2010

Trial name or titleLybrido(s) and SSRIs @Home: a double-blind, randomised, cross-over, placebo-controlled study to investigate the subjective and physiological efficacy and safety of Lybrido and Lybridos in the domestic setting in healthy women with female sexual dysfunction in combination with SSRI use. - @HOME

MethodsCross-over design in which a placebo regime (duration 4 weeks), the Lybrido regime (duration 4 weeks), and the Lybridos regime (duration 4 weeks) are separated by a 1- to 4-week washout period

ParticipantsTarget sample size: 40

Inclusion criteria: women 21-70 years old with hypoactive sexual desire disorder (comorbidity with other sexual dysfunctions e.g. Female Sexual Arousal Disorder (FSAD) allowed) or SSRI-induced sexual dysfunctioning, or both; at least 3 months use of an SSRI; SSRI must be on a stable dose for at least 6 weeks

Interventions1. Lybrido [combination testosterone and sildenafil], or

2. Lybridos [combination testosterone and buspirone], or

3. Placebo

OutcomesUnclear

Starting dateJanuary 2010

Contact informationEmotional Brain bv,

Louis Armstrongweg 78 

1311 RL 

Almere

The Netherlands

Notes

 
Comparison 1. Sildenafil vs placebo

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

 1 Endpoint International Index of Erectile Function (IIEF) scores3Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 Total score
2112Mean Difference (IV, Fixed, 95% CI)19.36 [15.00, 23.72]

    1.2 Erectile function (questions 1-5,15)
189Mean Difference (IV, Fixed, 95% CI)10.0 [7.39, 12.61]

    1.3 Question 3: ability to achieve erection
2231Mean Difference (IV, Fixed, 95% CI)1.04 [0.65, 1.44]

    1.4 Question 4: ability to maintain erection
2231Mean Difference (IV, Fixed, 95% CI)1.18 [0.78, 1.59]

    1.5 Intercourse satisfaction (questions 6, 7, 8)
189Mean Difference (IV, Fixed, 95% CI)3.50 [2.48, 4.52]

    1.6 Orgasmic function (questions 9, 10)
189Mean Difference (IV, Fixed, 95% CI)2.5 [1.36, 3.64]

    1.7 Sexual desire (questions 11, 12)
189Mean Difference (IV, Fixed, 95% CI)0.5 [-0.38, 1.38]

    1.8 Overall satisfaction (questions 13,14)
189Mean Difference (IV, Fixed, 95% CI)1.80 [0.86, 2.74]

 2 Endpoint Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Endpoint Clinical Global Impression - Sexual Function1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 Clinical Global Impression -Sexual Function not "much/very much improved" by endpoint2187Risk Ratio (M-H, Fixed, 95% CI)0.44 [0.33, 0.58]

    4.1 Males
189Risk Ratio (M-H, Fixed, 95% CI)0.48 [0.34, 0.66]

    4.2 Females
198Risk Ratio (M-H, Fixed, 95% CI)0.39 [0.24, 0.62]

 5 Endpoint Arizona Sexual Experience Scale (ASEX) total scores3210Mean Difference (IV, Fixed, 95% CI)-2.65 [-3.86, -1.44]

    5.1 Males
2112Mean Difference (IV, Fixed, 95% CI)-4.62 [-6.29, -2.95]

    5.2 Females
198Mean Difference (IV, Fixed, 95% CI)-0.5 [-2.24, 1.24]

 6 Males: endpoint Arizona Sexual Experience Scale scores2Mean Difference (IV, Fixed, 95% CI)Subtotals only

    6.1 Total score
2112Mean Difference (IV, Fixed, 95% CI)-4.62 [-6.29, -2.95]

    6.2 Sexual desire
189Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.08, -0.12]

    6.3 Arousal
189Mean Difference (IV, Fixed, 95% CI)-0.60 [-1.06, -0.14]

    6.4 Erectile function
189Mean Difference (IV, Fixed, 95% CI)-1.20 [-1.66, -0.74]

    6.5 Orgasm (ability)
189Mean Difference (IV, Fixed, 95% CI)-1.40 [-1.90, -0.90]

    6.6 Orgasm (satisfaction)
189Mean Difference (IV, Fixed, 95% CI)-1.0 [-1.58, -0.42]

 7 Endpoint MGH-Sexual Functioning Questionnaire scores1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.2 Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.3 Arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.4 Erectile function
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.5 Orgasm (ability)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    7.6 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Sexual dysfunction defined by Arizona Sexual Experience Scale at trial endpoint1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Dropouts4353Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.41, 1.14]

 10 Endpoint Hamilton Rating Scale for Depression score2187Mean Difference (IV, Fixed, 95% CI)-0.94 [-1.94, 0.07]

 11 Loss of remission: Hamilton Rating Scale for Depression score > 93330Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.04, 3.09]

 12 Global Efficacy Questionnaire (questions 1 & 2)1284Risk Ratio (M-H, Fixed, 95% CI)2.53 [1.90, 3.35]

    12.1 Improvement in erections
1142Risk Ratio (M-H, Fixed, 95% CI)2.5 [1.67, 3.73]

    12.2 Improvement in ability to have sexual intercourse
1142Risk Ratio (M-H, Fixed, 95% CI)2.55 [1.71, 3.80]

 13 Global efficacy questionnaire (question 3)1129Mean Difference (IV, Fixed, 95% CI)1.2 [0.65, 1.75]

    13.1 Question 3: Frequency of erection that allowed satisfactory sexual intercourse
1129Mean Difference (IV, Fixed, 95% CI)1.2 [0.65, 1.75]

 14 Endpoint Sexual Function Questionnaire (SFQ)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    14.1 Desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.2 Arousal-sensation
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.3 Arousal-lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.4 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.5 Enjoyment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.6 Pain
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    14.7 Partner
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 15 UNM Sexual Function Inventory1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    15.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    15.2 Desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    15.3 Sexual arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    15.4 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    15.5 Ability to reach orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    15.6 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 16 Females: endpoint Arizona Sexual Experience Scale scores1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    16.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    16.2 Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    16.3 Arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    16.4 Orgasm (ability)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    16.5 Orgasm (satisfaction)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    16.6 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Tadalafil vs placebo

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

 1 Global Assessment Questions1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Has the treatment you have been taking improved your erectile function?
150Risk Ratio (M-H, Fixed, 95% CI)11.5 [3.03, 43.67]

    1.2 Has the treatment improved your ability to engage in sexual activity?
150Risk Ratio (M-H, Fixed, 95% CI)11.5 [3.03, 43.67]

 2 Endpoint Sexual Encounter Profile (SEP)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Question 2:  Were you able to insert your penis into your partner's vagina?
150Risk Ratio (M-H, Fixed, 95% CI)2.33 [0.68, 8.01]

    2.2 Question 3: Did your erection last long enough for you to have successful intercourse?
150Risk Ratio (M-H, Fixed, 95% CI)6.0 [0.78, 46.29]

    2.3 Question 4: Were you satisfied with the hardness of your erection?
150Risk Ratio (M-H, Fixed, 95% CI)6.0 [0.78, 46.29]

    2.4 Question 5: Were you satisfied overall with this sexual experience?
150Risk Ratio (M-H, Fixed, 95% CI)6.0 [0.78, 46.29]

 3 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Overall
154Risk Ratio (M-H, Fixed, 95% CI)0.36 [0.04, 3.24]

    3.2 Lack of efficacy
154Risk Ratio (M-H, Fixed, 95% CI)0.36 [0.04, 3.24]

    3.3 Adverse effects
154Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Bupropion vs placebo

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

 1 Endpoint scale total scores3482Std. Mean Difference (IV, Fixed, 95% CI)1.60 [1.40, 1.81]

    1.1 International Index of Erectile Function (IIEF)
1227Std. Mean Difference (IV, Fixed, 95% CI)1.76 [1.45, 2.07]

    1.2 Female Sexual Function Index (FSFI)
1213Std. Mean Difference (IV, Fixed, 95% CI)1.73 [1.41, 2.05]

    1.3 Changes in Sexual Functioning Questionnaire (CSFQ)
142Std. Mean Difference (IV, Fixed, 95% CI)0.50 [-0.11, 1.12]

 2 Response (as defined by study)3284Risk Ratio (M-H, Fixed, 95% CI)31.77 [10.10, 99.89]

    2.1 50% reduction Arizona Sexual Experiences Scale (ASEX)
271Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.09, 4.41]

    2.2 Clinical Global Impression (CGI-SF) 2-point improvement
1213Risk Ratio (M-H, Fixed, 95% CI)186.73 [11.74, 2969.23]

 3 Endpoint International Index of Erectile Function (IIEF)1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    3.1 Total score
1227Mean Difference (IV, Fixed, 95% CI)20.10 [17.14, 23.06]

    3.2 Erectile function
1227Mean Difference (IV, Fixed, 95% CI)9.30 [8.18, 10.42]

    3.3 Orgasmic function
1227Mean Difference (IV, Fixed, 95% CI)2.70 [2.15, 3.25]

    3.4 Sexual desire
1227Mean Difference (IV, Fixed, 95% CI)2.10 [1.76, 2.44]

    3.5 Intercourse satisfaction
1227Mean Difference (IV, Fixed, 95% CI)3.6 [3.00, 4.20]

    3.6 Overall satisfaction
1227Mean Difference (IV, Fixed, 95% CI)2.60 [1.99, 3.21]

 4 Endpoint Female Sexual Function Index score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.3 Arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.4 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.5 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.6 Satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.7 Pain
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Endpoint Changes in Sexual Functioning Questionnaire score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.2 Desire/interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.3 Desire/frequency
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.4 Arousal/excitement
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    5.5 Completion/orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Dropouts5579Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.67, 1.72]

 7 Endpoint Hamilton Rating Scale for Depression score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 8 Endpoint Clinical Global Impression (CGI - SF)2440Mean Difference (IV, Fixed, 95% CI)-1.74 [-1.87, -1.61]

    8.1 Male
1227Mean Difference (IV, Fixed, 95% CI)-1.5 [-1.80, -1.20]

    8.2 Female
1213Mean Difference (IV, Fixed, 95% CI)-1.80 [-1.95, -1.65]

 9 Endpoint ASEX1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    9.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.2 Erectile function
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.3 Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.4 Arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.5 Ability to reach orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    9.6 Satisfaction with orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Endpoint EDITS (participant)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    10.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.2 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.3 Expectations
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.4 Likelihood of continuing
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.5 Confidence
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.6 Partner satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.7 Partner desire to continue treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.8 Naturalness of achieving erection
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.9 Naturalness of erection hardness
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.10 Quickness of achieving erection
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.11 Duration that erection lasts
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    10.12 Ease of use
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 11 Endpoint EDITS (partner)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    11.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.2 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.3 Expectations
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.4 Sexual desirability
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.5 Participant's feelings about continuing treatment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    11.6 Duration that erection lasts
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 4. Nefazodone vs sertraline

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

 1 Re-emergence of antidepressant-induced sexual dysfunction (physician rated)1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Week 1
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Endpoint
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Overall degree of sexual satisfaction (participant rated)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Baseline
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Week 8
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Last rating recorded
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 Overall
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Attributed to adverse effects
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Hamilton Rating Scale for Depression score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Baseline
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Week 8
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 5. Ginkgo biloba vs placebo

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

 1 Endpoint sexual function ratings (investigator questionnaire)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Overall sexual function
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Erection maintenance time
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Orgasm frequency
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Satisfaction to orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Sexual Dysfunction Scale (investigator developed)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Baseline
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Week 12
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 6. Granisetron vs placebo

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

 1 Change from baseline on Sexual Side Effects Scale (SSES) total score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 2 Endpoint Feiger Sexual Function and Satisfaction Questionnaire score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Item 1
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Item 2
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 Item 3
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.5 Item 4
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.6 Item 5
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.7 Item 6
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Endpoint Arizona Sexual Experience Scale (ASEX) score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.2 Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.3 Arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.4 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.5 Orgasm (ability)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    3.6 Orgasm (satisfaction)
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Recurrence of mood symptoms143Risk Ratio (M-H, Fixed, 95% CI)2.87 [0.12, 66.75]

 
Comparison 7. VML-670 vs placebo

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

 1 Absence of sexual dysfunction at end point1266Risk Ratio (M-H, Fixed, 95% CI)1.24 [0.86, 1.77]

 2 'Improved' or 'much improved' on Clinical Global Impression1266Risk Ratio (M-H, Fixed, 95% CI)1.24 [0.71, 2.17]

 3 Change in Arizona Sexual Experiences Scale (ASEX) item scores11264Mean Difference (IV, Fixed, 95% CI)-0.07 [-0.19, 0.05]

    3.1 How strong is your sexual drive?
1255Mean Difference (IV, Fixed, 95% CI)-0.10 [-0.36, 0.16]

    3.2 How easily are you sexually aroused?
1253Mean Difference (IV, Fixed, 95% CI)-0.20 [-0.47, 0.07]

    3.3 Females: how easily does your vagina become moist or wet?
1180Mean Difference (IV, Fixed, 95% CI)0.10 [-0.22, 0.42]

    3.4 Males: can you easily get and keep an erection?
172Mean Difference (IV, Fixed, 95% CI)-0.4 [-0.80, 0.00]

    3.5 How easily can you reach orgasm?
1252Mean Difference (IV, Fixed, 95% CI)0.0 [-0.28, 0.28]

    3.6 Are your orgasms satisfying?
1252Mean Difference (IV, Fixed, 95% CI)0.10 [-0.22, 0.42]

 4 Dropouts1532Risk Ratio (M-H, Fixed, 95% CI)1.19 [0.73, 1.93]

    4.1 Total
1266Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.56, 1.68]

    4.2 Attributed to adverse effects
1266Risk Ratio (M-H, Fixed, 95% CI)2.32 [0.75, 7.21]

 
Comparison 8. Buspirone vs placebo

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

 1 Change in patient-rated visual analogue scales1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 Overall function (total of interest, lubrication, orgasm, pleasure)
139Mean Difference (IV, Fixed, 95% CI)3.10 [-38.33, 44.53]

    1.2 Mood
139Mean Difference (IV, Fixed, 95% CI)0.80 [-7.61, 9.21]

    1.3 Energy
139Mean Difference (IV, Fixed, 95% CI)5.30 [-3.88, 14.48]

    1.4 Interest/desire
139Mean Difference (IV, Fixed, 95% CI)2.70 [-7.99, 13.39]

    1.5 Lubrication
139Mean Difference (IV, Fixed, 95% CI)9.90 [-3.65, 23.45]

    1.6 Orgasm
139Mean Difference (IV, Fixed, 95% CI)-6.3 [-19.98, 7.38]

    1.7 Pleasure
139Mean Difference (IV, Fixed, 95% CI)-3.20 [-15.53, 9.13]

    1.8 Discomfort
139Mean Difference (IV, Fixed, 95% CI)7.00 [-3.15, 17.15]

 2 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 9. Bethanecol vs placebo

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

 1 Visual analogue scale of orgasmic function - best score achieved1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Comparison 10. Olanzapine vs placebo

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

 1 Change in patient rated assessment of sexual function1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Sexual interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Psychological arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Change in diary ratings (visual analogue scales)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Overall sexual function
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Mood
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Energy
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 Sexual interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.5 Psychological arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.6 Physical arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.7 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.8 Pleasure/enjoyment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.9 Discomfort
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Dropouts due to adverse effects1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 11. Mirtazapine vs placebo

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

 1 Change in patient rated assessment of sexual function1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Sexual interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Psychological arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Change in diary ratings (visual analogue scales)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Overall sexual function
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Mood
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Energy
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 Sexual interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.5 Psychological arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.6 Physical arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.7 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.8 Pleasure/enjoyment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.9 Discomfort
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Endpoint modified Kinsey Structured Interview175Mean Difference (IV, Fixed, 95% CI)0.60 [0.19, 1.01]

    3.1 Sexual satisfaction
175Mean Difference (IV, Fixed, 95% CI)0.60 [0.19, 1.01]

 4 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    4.1 Attributed to adverse effects
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 12. Yohimbine vs placebo

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

 1 Change in patient rated assessment of sexual function1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Overall satisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Sexual interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Psychological arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Change in diary ratings (visual analogue scales)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Overall sexual function
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Mood
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Energy
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.4 Sexual interest
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.5 Psychological arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.6 Physical arousal
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.7 Orgasm
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.8 Pleasure/enjoyment
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.9 Discomfort
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    3.1 Attributed to adverse effects
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 13. Amantadine vs placebo

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

 1 Change in patient-rated visual analogue scales1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    1.1 Overall function (total of interest, lubrication, orgasm, pleasure)
138Mean Difference (IV, Fixed, 95% CI)13.0 [-29.02, 55.02]

    1.2 Mood
138Mean Difference (IV, Fixed, 95% CI)8.1 [1.23, 14.97]

    1.3 Energy
138Mean Difference (IV, Fixed, 95% CI)12.7 [5.30, 20.10]

    1.4 Interest/desire
138Mean Difference (IV, Fixed, 95% CI)0.90 [-7.96, 9.76]

    1.5 Lubrication
138Mean Difference (IV, Fixed, 95% CI)7.90 [-5.74, 21.54]

    1.6 Orgasm
138Mean Difference (IV, Fixed, 95% CI)2.50 [-11.91, 16.91]

    1.7 Pleasure
138Mean Difference (IV, Fixed, 95% CI)1.70 [-11.28, 14.68]

    1.8 Discomfort
138Mean Difference (IV, Fixed, 95% CI)1.30 [-11.25, 13.85]

 2 Dropouts1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 14. ephedrine vs placebo

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

 1 Endpoint Brief Index of Sexual Functioning for Women (BISF-W)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Sexual arousability
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.3 Lack of vaginal lubrication
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.4 Orgasm ability
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.5 Orgasm intensity/pleasure
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.6 Sexual dissatisfaction
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 15. Maca root: high vs low dose

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

 1 Endpoint Arizona Sexual Experiences Scale (ASEX) score1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Question 1: Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Endpoint MGH-SFQ1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 Total score
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Item a: Sexual desire
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Dropouts120Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.60, 3.74]

 4 Endpoint ratings of psychiatric symptoms1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    4.1 Hamilton Depression Rating Scale
116Mean Difference (IV, Fixed, 95% CI)-2.5 [-7.98, 2.98]

    4.2 Hamilton Anxiety Rating Scale
116Mean Difference (IV, Fixed, 95% CI)-0.40 [-3.15, 2.35]

 
Summary of findings for the main comparison. Sildenafil versus placebo

Sildenafil compared with placebo for antidepressant-induced sexual dysfunction

Patient or population: people with antidepressant-induced sexual dysfunction

Settings: outpatient

Intervention: sildenafil

Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(no of studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboSildenafil

Endpoint International Index of Erectile Function (IIEF) total scores

(The IIEF is a self-report measure with 15 questions examining erectile function, orgasmic function, sexual desire, and intercourse satisfaction. Maximum possible score 75)
The mean IIEF score ranged across control groups from
40.9 to 44.2
The mean IIEF score in the intervention groups was
19.36 higher (15.00 to 23.72 higher)
112 men
(2 studies)
⊕⊕⊕⊕
high

Endpoint International Index of Erectile Function (IIEF) scores - question 3: ability to achieve erection

(Maximum score 5)
The mean score in control groups was 3.1The mean score in the intervention groups was
1.04 higher (0.65 to 1.44 higher)
231 men
(2 studies)
⊕⊕⊕⊕
high

Endpoint International Index of Erectile Function (IIEF) scores - intercourse satisfaction (questions 6, 7, 8)

(Maximum score 15)
The mean score in the control group was 7.2The mean score in the intervention group was
3.50 higher (2.48 to 4.52 higher)
89 men
(1 study)
⊕⊕⊕⊝
moderate

Clinical Global Impression -Sexual Function not "much/very much improved" by endpointMale populationRR 0.44 (0.33 to 0.58)187
(2 studies)
⊕⊕⊕⊝
moderate

956 per 1000459 per 1000
(325 to 630)

Female population

735 per 1000287 per 1000
(176 to 456)

Dropouts

(People leaving the trial early)
Low risk populationRR 0.68 (0.41 to 1.14)353
(4 studies)
⊕⊕⊕⊕
high

90 per 100061 per 1000
(37 to 103)

Medium risk population

250 per 1000170 per 1000
(102 to 285)

High risk population

360 per 1000245 per 1000
(148 to 411)

Global Efficacy Questionnaire (questions 1 & 2)

(Questions assessing improvement attributed to medication compared to having no treatment at all)
Improvement in erectionsRR 2.50 (1.67 to 3.73)

and

RR 2.55 (1.71 to 3.80)
284 men
(1 study)
⊕⊕⊕⊝
moderate

282 per 1000705 per 1000
(470 to 1000)

Improvement in ability to have sexual intercourse

282 per 1000719 per 1000
(482 to 1000)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

 The evidence for effects based on single trials is rated as moderate quality since further trial data may well change the estimate.
 
Summary of findings 2. Bupropion versus placebo

Bupropion compared with placebo for antidepressant-induced sexual dysfunction

Patient or population: people with antidepressant-induced sexual dysfunction

Settings: outpatients

Intervention: bupropion (doses of 150 mg daily and 150 mg twice daily)

Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(no of studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboBupropion

Endpoint scale total scores (150 mg twice daily dose)

(Scales of sexual functioning. As studies used different scales to assess sexual functioning, differences are expressed as standardised mean differences (SMD))
The mean value with this analysis is in effect zeroThe mean score in the intervention groups was 1.60 higher (1.40 to 1.81)482
(3 studies)
⊕⊕⊕⊝
moderate1

50% reduction in score on the Arizona Sexual Experiences Scale (ASEX) (150 mg once daily dose)

(The ASEX is a 5-item self-report inventory of sexual function)
Lower risk populationRR 0.62 (0.09 to 4.41)71
(2 studies)
⊕⊕⊕⊝
moderate

47 per 100029 per 1000
(4 to 208)

Higher risk population

67 per 100041 per 1000
(6 to 296)

Dropouts

(People leaving the trial early)
Lower risk populationRR 1.08 (0.67 to 1.72)579
(5 studies)
⊕⊕⊕⊕
high

90 per 100097 per 1000
(60 to 155)

Higher risk population

150 per 1000162 per 1000
(100 to 258)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

 1 Unexplained inconsistency in effects between studies reduces confidence in this effect