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Selective serotonin reuptake inhibitors for premenstrual syndrome

  1. Jane Marjoribanks1,
  2. Julie Brown1,*,
  3. Patrick Michael Shaughn O'Brien2,
  4. Katrina Wyatt3

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 7 JUN 2013

Assessed as up-to-date: 11 FEB 2013

DOI: 10.1002/14651858.CD001396.pub3


How to Cite

Marjoribanks J, Brown J, O'Brien PMS, Wyatt K. Selective serotonin reuptake inhibitors for premenstrual syndrome. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD001396. DOI: 10.1002/14651858.CD001396.pub3.

Author Information

  1. 1

    University of Auckland, Obstetrics and Gynaecology, Auckland, New Zealand

  2. 2

    Keele University Medical School, Academic Department of Obstetrics and Gynaecology, Stoke-on-Trent, Staffordshire, UK

  3. 3

    Peninsula College of Medicine and Dentistry, Institute of Health Service Research, Exeter, UK

*Julie Brown, Obstetrics and Gynaecology, University of Auckland, Park Rd, Grafton, Auckland, 1003, New Zealand. j.brown@auckland.ac.nz.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 7 JUN 2013

SEARCH

 

Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 
Summary of findings for the main comparison. SSRIs for premenstrual syndrome: all symptoms (end scores)

SSRIs compared to placebo - all symptoms (end scores) for premenstrual syndrome

Patient or population: women with premenstrual syndrome
Settings: community or outpatient
Intervention: SSRIs
Comparison: placebo - all symptoms (end scores)

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

Moderate dose SSRI

versus placebo

Luteal or continuous administration
The mean score for all symptoms in the intervention groups was
0.67 standard deviations lower
(0.46 to 0.84 lower)
1276
(9 studies)
⊕⊕⊝⊝
low1,2
SMD -0.65 (95% CI -0.42 to -0.84)

Symptoms were significantly less severe in the SSRI group. The size of the effect was moderate.

Moderate dose SSRI

versus placebo

Luteal administration
The mean score for all symptoms in the intervention groups was
0.51 standard deviations lower
(0.71 to 0.31 lower)
457
(4 studies)
⊕⊕⊕⊝
moderate2
SMD 0.51 (95% CI -0.71 to -0.31)

Symptoms were significantly less severe in the SSRI group. The size of the effect was moderate.

Moderate dose SSRI versus placebo Continuous administration The mean score for all symptoms in the intervention groups was
0.72 standard deviations lower
(0.97 to 0.47 lower)
843
(7 studies)
⊕⊕⊝⊝
low1,2
SMD -0.72 (95% CI -0.97 to -0.47)

Symptoms were significantly less severe in the SSRI group. The size of the effect was moderate.

*The basis for the assumed risk is the median control group risk across studies. 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; SMD standardised mean difference

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 Only 4/9 studies overall (2/4 of luteal and 3/7 of continuous administration) described adequate methods of randomisation and allocation concealment; 8/9 studies were at uncertain or high risk of attrition bias.
2 Substantial overall heterogeneity (I squared= 58%), attributable to heterogeneity in continuous administration group (I squared=68%), which included two studies with larger intervention effects. No obvious explanation (though studies used wide variety of assessment tools).

 Summary of findings 2 SSRIs for premenstrual syndrome: all symptoms (change scores)

 Summary of findings 3 SSRIs for premenstrual syndrome: withdrawal due to adverse effects

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of the condition

Most women of reproductive age experience premenstrual symptoms that are associated with the rise and fall of ovarian sex steroids precipitated by ovulation (Rapkin 2008). Premenstrual syndrome (PMS) is distinguished from 'normal' premenstrual symptoms by the degree of distress it causes or its detrimental effect on daily functioning, or both (O'Brien 2011). The physiology of PMS is complex and the disorder is poorly understood (Freeman 2012). It may be associated with the actions of serotonin and gamma-aminobutyric acid, which are neurotransmitters influenced by the menstrual cycle. Abnormal function or deficiency of these neurotransmitters may cause increased sensitivity to progesterone, precipitating PMS symptoms (Baker 2012).

Definitions of PMS vary, and a wide range of psychological and physical symptoms has been reported. The key characteristic of PMS is the timing of symptoms, which occur only during all or part of the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Symptoms disappear by the end of menstruation and do not recur before ovulation, giving a symptom-free interval of at least one week. PMS is cyclical, and occurs in most menstrual cycles (O'Brien 2011). Psychological symptoms can include irritability, depression, anxiety, mood swings, a flat mood (anhedonia) and lethargy. Physical symptoms may include breast tenderness, weight gain, bloating, muscle or joint pain, headache and swelling of the extremities (hands and feet). A clinical diagnosis requires that symptoms are confirmed by prospective recording for at least two menstrual cycles and that they cause substantial distress or impairment to daily life (for example activities at home, work or school, social activities, hobbies, interpersonal relationships) (ACOG 2000; Baker 2012; Epperson 2012; O'Brien 2011). As collecting multiple, daily data points is a laborious process, most diagnoses of PMS are made based on a woman's own perception of her problem. Hence it is suggested that up to 50% of women with reported PMS do not meet the clinical criteria for the disorder (Plouffe 1993). PMS in this review is defined as symptoms meeting the clinical criteria described above.

A severe form of PMS is known as premenstrual dysphoria or premenstrual dysphoric disorder (PMDD), and was previously also known as late luteal phase dysphoric disorder (LLPDD) (O'Brien 2011). PMDD is characterised by severe symptoms occurring for a week before each menstrual period and remitting in the week after menstruation, over a period of at least a year. According to American Psychiatric Association (APA) criteria, in their Diagnostic and Statistical Manual version 4 (DSM IV), at least five of the following symptoms must occur for most of the week prior to menstruation: depression, anxiety, mood swings, irritability (at least one of these four), decreased interest in usual activities, difficulty concentrating, fatigue, appetite changes, sleep disturbance, feeling overwhelmed, and physical symptoms (APA 2000). Symptoms should remit within a few days of menstruation. This definition has been questioned because it focuses on severe psychological symptoms while placing relatively little importance on physical symptoms, and may exclude some women with debilitating symptoms that do not meet these specific criteria (O'Brien 2011).

DSM criteria are currently being updated to include PMDD as a new diagnostic category rather than (as previously) a mood disorder needing further research. Although the proposed DSM V criteria for PMDD are similar to those of DSM IV, they differ in the following respects (Epperson 2012):

  • symptoms must occur during the final week before menstruation, but do not need to be present most of the time;
  • symptoms are not required to remit within a few days of menstruation, but should improve and should be minimal (if not absent) in the week following menstruation;
  • mood lability and irritability are the leading two symptoms;
  • symptoms cause clinically significant distress or interference with activities at work or school or at home, or both (previously there was no mention of clinically significant distress or of activities at home);
  • PMDD symptoms are not due to an ongoing medical disorder or substance-induced condition.

There is a wide variation in estimates of the prevalence of PMS, but it is estimated that 15% to 20% of women of reproductive age have PMS with significantly impaired functioning, and a further 3% to 8% have PMDD. Thus approximately one in five women of reproductive age are affected (Pearlstein 2007).

There is currently no haematological or biochemical test for PMS, and studies have not shown consistent differences in cyclical hormone levels. In the absence of any objective parameter to measure or diagnose PMD, clinicians and researchers rely largely on validated scales in which a woman self-rates her symptoms. The most widely used self-rating tool is the Daily Record of Severity of Problems (DRSP), which is a prospective scale that focuses largely on psychological rather than physical symptoms (O'Brien 2011).

 

Description of the intervention

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are believed to inhibit the absorption of serotonin, a naturally occurring chemical which acts as a messenger between brain cells (a neurotransmitter). Changing the balance of serotonin appears to improve neurotransmission and enhance mood.

SSRIs are most commonly used to treat depression and anxiety disorders, and appear to take four to eight weeks to reach clinical efficacy in these disorders (Freeman 1999). However, it has been shown that SSRIs may become effective for PMS in a matter of days, and usually within four weeks from the start of treatment (Steiner 1995). This may be due to the cyclical nature of PMS and may reflect SSRI action at a different receptor site to that involved in affective disorders (Sundblad 1997).

The rapid efficacy of SSRI treatment in PMS permits the use of intermittent dosing regimens. For treatment of PMS a relatively small dose of SSRI is generally used. Administration can be:

  • continuous, SSRI is taken every day throughout the menstrual cycle;
  • luteal or intermittent, SSRI is taken only during the luteal phase of the menstrual cycle (i.e. from estimated ovulation to menstruation). The SSRI is started about 14 days prior to expected menstruation, based on a woman's usual cycle length;
  • semi-intermittent, taken every day, with a low SSRI dose during the follicular phase of the menstrual cycle and a higher dose in the luteal phase;
  • as required, SSRI is started at the onset of PMS symptoms and continued until the onset of menstruation.

It is suggested that avoidance of continuous use may reduce the risk of side effects of SSRIs, which can include anxiety, dizziness, insomnia, sedation, gastrointestinal disturbance, headache, loss of libido and anorgasmia (inability to achieve orgasm) (Baker 2012; Pearlstein 2002).

SSRIs are licensed for treating PMMD in the United States, but not in Europe (Ismail 2006).

Other interventions used for premenstrual symptoms include lifestyle modification (for example exercise, smoking cessation, weight management), herbal remedies (for example vitex agnus castus), calcium, vitamin C, hormones, gonadotrophin-releasing hormone (GnRH) analogues, danazol and (rarely and as a last resort) hysterectomy with bilateral oophorectomy (Baker 2012). Uncertainty about the pathogenesis of PMS has led to many other treatments being suggested as possible therapies. It has been suggested that, as there is a substantial placebo response, a large number of uncontrolled trials have resulted in a proliferation of claims for ineffective therapies (Magos 1986).

Different PMS symptoms may have separate causes and therefore require different treatment strategies (O'Brien 2011). It is suggested that most women with severe PMS require either hormonal medication (estrogen with or without progestin) or a psychotropic medication (such as an SSRI) for symptom relief (Baker 2012). As the disorder is usually chronic, and may require treatment for 20 years or more, the long-term effects of an intervention are important (Rapkin 2008).

Some of the interventions are the subject of other Cochrane reviews, either published or in preparation (as of April 2013), as follows.

  • Oral contraceptives containing drosperinone

This review found that drospirenone 3 mg plus ethinyl estradiol 20 μg may be beneficial for PMDD. It was unclear whether oral contraceptives containing drospirenone were effective for women with less severe symptoms, or were better than other oral contraceptives. A strong placebo effect was noted (Lopez 2012).

  • Chinese herbal medicines

This review found that there was insufficient evidence to support the use of Chinese herbal medicines for PMS (Jing 2009).

  • Progesterone

This review found that it was unclear whether or not progesterone is an effective treatment for PMS (Ford 2012).

  • Acupuncture

This review is in preparation. The protocol has been published (Yu 2005).

  • Vitex agnus castus

This review is in preparation. The protocol has been published (Shaw 2003).

  • Non-contraceptive estrogen-containing preparations for controlling symptoms of PMS

This review is in preparation. The protocol has been published (Naheed 2013).

 

How the intervention might work

Serotonin levels appear to vary during the menstrual cycle under the influence of estrogen and progesterone (Baker 2012). SSRIs may increase the amount of serotonin available for neurotransmission.

It has been noted that treatments that enhance the action of serotonin improve premenstrual irritability and low mood with a rapid onset of action, which suggests a different mechanism of action than in the treatment of depression. Neurosteroids such as progesterone metabolites may be responsible for the rapid action of SSRIs in this context (Pearlstein 2002).

 

Why it is important to do this review

In view of the debilitating symptoms and economic cost of PMS, and the likelihood that it will persist long-term, it is important to confirm and quantify the effectiveness and safety of SSRIs for treating this disorder. This is an update of a Cochrane review first published in 2002.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

To determine the effectiveness and safety of SSRIs for treating premenstrual syndrome.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Criteria for considering studies for this review

 

Types of studies

Published and unpublished randomised controlled trials (RCTs) were eligible for inclusion. We excluded non-randomised studies (for example studies with evidence of inadequate sequence generation such as alternate days, patient numbers) as they are associated with a high risk of bias. Crossover trials were eligible but it was planned that only data from the first phase would be included in meta-analyses.

 

Types of participants

Studies of women of any age who met the medically defined diagnostic criteria for premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD) were eligible for inclusion. Diagnosis must have been made prior to inclusion in the trial by a general practitioner (GP), hospital clinician, or other healthcare professional. Diagnosis of PMS requires that symptoms are confirmed by prospective recording for at least two menstrual cycles and must cause substantial distress or impairment to daily life. Diagnosis of PMDD must meet established psychiatric diagnostic criteria.

Studies of women with only a self-diagnosis of PMS were excluded.

 

Types of interventions

Studies of SSRIs, at any dose and in any dosing regimen for any duration longer than one menstrual cycle, versus placebo were eligible.

Trials of tricyclic antidepressants were excluded. Even when described as serotonin reuptake inhibitors, these drugs are not selective and act in a different manner to SSRIs.

 

Types of outcome measures

 
Primary

1. Self-rated overall premenstrual symptoms, measured using a validated prospective screening tool (e.g. Moos' MDQ, Abraham's classification) or by pre-defined medical diagnostic criteria

2. Adverse events (all adverse events, specific adverse effects, withdrawals for adverse effects)

 
Secondary

3. Specific symptoms of PMS: psychological, physical and functional symptoms, irritability

4. Response rate (according to how response defined in individual studies)

5. Overall withdrawals from study

 

Search methods for identification of studies

We searched for all published and unpublished RCTs meeting the inclusion criteria. The search was conducted without language restriction and in consultation with the Menstrual Disorders and Subfertility Group Trials Search Co-ordinator.

 

Electronic searches

For the latest search (February 2013), we searched the following electronic databases, trials registers and websites: Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of Controlled Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO.

Other electronic sources of trials included:
a. trials registers for ongoing and registered trials, http://www.controlled-trials.com, http://clinicaltrials.gov/ct2/home, http://www.who.int/trialsearch/Default.aspx;
b. Web of Knowledge (including the citation database Web of Science).

For versions of the review prior to 2013, we also searched http://www.clinicalstudyresults.org/ for the results of clinical trials of marketed pharmaceuticals. However, this database has not been accessible since June 2012.

See Appendix 1; Appendix 2; Appendix 3 for database search strategies.

 

Searching other resources

a) We handsearched the reference lists of articles retrieved by the search.

b) For the 2002 version of this review:

  • drug and pharmaceutical companies manufacturing SSRIs (fluoxetine: Eli Lilly; paroxetine: Smith Kline Beecham; sertraline: Invicta; fluvoxamine: Solvay; Citalopram: Du Pont) were contacted to request other published or unpublished trials;
  • the personal databases on PMS therapies maintained by the authors were searched for relevant articles;
  • the UK-based National Association for Premenstrual Syndrome (NAPS) was also contacted for relevant articles.

c) For the 2013 version of this review:

  • attempts were made to contact the following drug and pharmaceutical companies manufacturing SSRIs (Lilly, GlaxoSmithKline, Pfizer, Forest Labs) to request other published or unpublished trials. However, only one company (GlaxoSmithKline) replied.

 

Data collection and analysis

 

Selection of studies

 
The 2013 update

For the 2013 update of this review, JM conducted an initial screen of titles and abstracts retrieved by the search and retrieved the full texts of all potentially eligible studies. Two review authors (JM and KMW) independently examined these full text articles for compliance with the inclusion criteria and selected studies eligible for inclusion. We corresponded with study investigators, as required, to clarify study eligibility. Disagreements as to study eligibility were resolved by discussion or by a third review author.

 
Previous versions of the review

For the original version of this review (2002), all publications identified in the search strategy were assessed by two authors (PWD and KMW) working in parallel. Selection of the trials for inclusion was performed by PWD and KW. Any disagreements were assessed by a third review author and other uncertainties regarding inclusion were resolved by contacting the primary study authors. For the 2008 update of the review, an additional 22 studies were identified by JB and JM, who independently checked the potentially eligible studies.

 

Data extraction and management

For the 2013 update of this review, two review authors (JM and JB) independently extracted data from the eligible studies. Any disagreements were resolved by discussion or by a third review author. Data extracted included study characteristics and effect estimates.

Where there were multiple arms in a study with a common placebo, the placebo numbers were divided as equally as possible between the arms (see footnotes in forest plots).

Where studies had multiple publications, the main trial report was used as the reference and additional details were derived from secondary papers. We corresponded with study investigators for further data on methods and results, as required.

 

Assessment of risk of bias in included studies

For the 2008 and 2013 updates, two review authors independently assessed the included studies for risk of bias using the Cochrane risk of bias assessment tool (Higgins 2011). This assesses: allocation (random sequence generation and allocation concealment); blinding of participants and personnel, blinding of outcome assessors; and completeness of outcome data.

For the 2013 update, new studies were also assessed for risk of selective reporting bias, which refers to the selective reporting of some outcomes (for example positive outcomes) and the failure to report others (for example adverse events), and for other potential sources of bias.

Disagreements were resolved by discussion or by a third review author. We described all judgements fully and presented the conclusions in the 'Risk of bias' table. Differences in study quality were incorporated into the interpretation of review findings by means of sensitivity analyses.

 

Measures of treatment effect

For continuous data (for example symptom scores), as similar outcomes were reported on different scales, we calculated the standardised mean difference (SMD) between the end scores or change scores for the control and intervention groups of each study. End scores were extracted in preference to change scores, where available, as they may be preferable for outcomes which are unstable or difficult to measure precisely (Higgins 2011). For dichotomous data (for example withdrawal rates), we used the numbers of events in the two groups to calculate Mantel-Haenszel odds ratios (ORs). We presented 95% confidence intervals (CIs) for all outcomes. We compared the magnitude and direction of effect reported by studies with how they were presented in the review, taking account of legitimate differences.

Where there was a statistically significant difference between the two groups in the rate of adverse events, we calculated numbers needed to harm (NNH) for the moderate dose (that is an estimate of the number of women who would need to receive treatment using a moderate dose in order for one additional harm to occur).

Standard mean differences were interpreted using the following rule of thumb: 0.2 represents a small effect, 0.5 a moderate effect, and 0.8 a large effect (Cohen 1988a; Higgins 2011).

 

Unit of analysis issues

We planned to include only first-phase data from crossover trials.

 

Dealing with missing data

The data were analysed on an intention-to-treat basis as far as possible and attempts were made to obtain missing data from the original trialists. Where these were unobtainable, only the available data were analysed.

 

Assessment of heterogeneity

We considered whether the clinical and methodological characteristics of the included studies were sufficiently similar for meta-analysis in order to provide a clinically meaningful summary. We assessed statistical heterogeneity by the I2 statistic.

A rough guide to interpretation of I2 values is as follows (Higgins 2011):

  •  0% to 40%, might not be important;
  • 30% to 60%, may represent moderate heterogeneity;
  • 50% to 90%, may represent substantial heterogeneity;
  • 75% to 100%, considerable heterogeneity.

 

Assessment of reporting biases

In view of the difficulty of detecting and correcting for publication bias and other reporting biases, we aimed to minimise their potential impact by ensuring a comprehensive search for eligible studies and by being alert for duplication of data.

If there were 10 or more studies in the analysis of a primary outcome, we used a funnel plot to explore the possibility of small study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies).

 

Data synthesis

If the studies were sufficiently similar, we combined the data using random-effects models to compare SSRIs versus placebo. The primary outcome was stratified by SSRI dose (low, moderate or high, see  Table 1) and by type of administration (luteal or continuous). The SMDs of end scores and change scores were analysed separately and were not pooled since the differences in the standard deviations reflect differences in the reliability of the measurements and not differences in measurement scales (Higgins 2011).

 

Subgroup analysis and investigation of heterogeneity

Where data were available, we conducted subgroup analyses to determine the separate evidence for the primary outcomes within the following subgroups:

  1. administration mode (continuous versus intermittent or as required);
  2. placebo run-in versus non-placebo run-in.

If we detected substantial heterogeneity (I2 > 50%), we planned to explore possible explanations by checking the data, conducting sensitivity analyses (see below), and by examining clinical and methodological differences between the studies, to check whether there was a plausible explanation. Where there were three or more studies using the same SSRI and dose we examined whether the findings differed in subgroups using the same SSRI. We planned to take statistical heterogeneity into account when interpreting the results, especially if there was any variation in the direction of effect.

 

Sensitivity analysis

We conducted sensitivity analyses for the primary outcomes to determine whether the conclusions were robust to arbitrary decisions made regarding the eligibility of the studies and analysis. These analyses included consideration of whether the review conclusions would have differed if:
1. eligibility was restricted to studies without high risk of bias, defined as studies at low risk of selection bias;
2. a fixed-effect model had been adopted.

 

Summary of findings table

A 'Summary of findings' table was generated using GRADEPRO software to evaluate the overall quality of the body of evidence for the main review outcomes, using GRADE working group criteria (that is study limitations (risk of bias), consistency of effect, imprecision, indirectness and publication bias). Judgements about the quality of the evidence (high, moderate or low) were justified, documented, and incorporated into reporting of results for each outcome.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Description of studies

 

Results of the search

 
Searches up to 2009

Ninety-six potentially relevant articles were retrieved in searches up to 2008. Twenty-eight studies were identified as RCTs that used SSRIs in the management of PMS and were included.

 
Search update in 2013

Nineteen potentially eligible articles were retrieved in the 2013 search. Six were included as new studies (Eriksson 2008; Freeman 2010; Glaxo 1996; Glaxo 1996a; Glaxo 2001; Steiner 2008) and three (Glaxo 2002; Miller 2008; Wu 2008) were excluded. Two articles were additional publications for included studies (Freeman 2004; Landen 2007), six were the abstracts of studies already included, and two were ongoing studies (Yonkers 2007; Yonkers 2010).

In the 2009 version of the review, the 28 included studies were divided into 40 comparisons each with a separate study reference. For the 2013 update, data relating to the same study were combined under a common study reference. Three previously included studies were excluded in the update after discussion between the review authors: one (Veeninga 1990) because the participants were self-diagnosed and did not clearly meet medically defined diagnostic criteria for PMS, and two (Sundblad 1992a; Sundblad 1993a) because the intervention was clomipramine, which is not an SSRI.

Thus, a total of 31 studies are now included (n = 4372 ), comprising 25 studies from the previous version of the review and six new studies. See the study flow diagram (Figure 1).

 FigureFigure 1. Study flow diagram.

 

Included studies

 

Study design and funding source

All studies were RCTs. Fifteen reported that they were multi-centred (Cohen 2002; Cohen 2004; Glaxo 1996; Glaxo 1996a; Glaxo 2001; Halbreich 2002; Kornstein 2006; Landen 2007; Miner 2002; Pearlstein 1997; Pearlstein 2005; Steiner 1995; Steiner 2005; Steiner 2008; Yonkers 1997).

Most studies were of parallel-group design but six used a crossover design (Halbreich 1997; Jermain 1999; Menkes 1992; Su 1997; Wood 1992; Young 1998). The first-arm data (before crossover) for overall symptom reduction could be extracted for only one of these trials (Jermain 1999); the remaining crossover trials were not used in the data pooling. Where data were incomplete, all authors were contacted. However, no additional data were received.

Twenty-one studies were solely or partially funded by pharmaceutical companies (Cohen 2002; Eriksson 1995; Eriksson 2008; Freeman 2010; Glaxo 1996; Glaxo 1996a; Glaxo 2001; Halbreich 1997; Halbreich 2002; Jermain 1999; Kornstein 2006; Landen 2007; Miner 2002; Pearlstein 1997; Pearlstein 2005, Steiner 1995; Steiner 2005; Steiner 2008; Stone 1991; Yonkers 1997) or had pharmaceutical company employees among their authors (Cohen 2004). Seven studies were funded independently (Freeman 1999; Freeman 2004; Menkes 1992; Su 1997; Wikander 1998; Wood 1992; Young 1998). The source of funding was unclear in three studies (Arrendondo 1997; Crnobaric 1998; Ozeren 1997).

 

Participants

Women in most of the included studies were aged from 18 to 45 years (range 18 to 49 years) where reported, though one study enrolled teenagers aged 15 to 19 years (Freeman 2010).

Most of the studies diagnosed women with PMS or PMDD by means of validated self-rating symptom scales completed over multiple menstrual cycles, or by means of psychiatric diagnostic criteria. Measures used were:

In most studies women were recruited from clinical settings (for example psychiatric, gynaecological or PMS outpatient clinics) or via media, television, or local newspaper advertising. Five studies provided no details of recruitment methods.

Exclusion criteria varied, but most of the studies excluded women with the following characteristics:

  • current or recent major or Axis 1 psychiatric diagnosis (other than PMDD);
  • other clinically significant disease;
  • recent hormonal contraceptive use;
  • current or planned pregnancy;
  • use of concurrent medication (including psychotropic drugs).

 

Interventions

 

Description of the interventions

SSRIs used were:

The timing regimen of the intervention varied as follows (some studies included more than one):

The number of treatment cycles for these interventions varied from two to six.

Three studies compared luteal versus continuous (Freeman 2004; Landen 2007; Wikander 1998) or semi-intermittent (Wikander 1998) SSRI dosing strategies. A fourth study (Kornstein 2006) included an 'as required' regimen, whereby women took an SSRI from symptom onset to menstruation. These data were not included in the review because the 'as required' regimen was administered after two cycles of luteal administration and had a duration of only one cycle, and thus did not meet our inclusion criteria.

Some of the studies had more than one active treatment arm. They included different drug doses (Cohen 2002; Cohen 2004; Eriksson 2008; Kornstein 2006; Steiner 1995; Steiner 2008; Wikander 1998) or different drug timing regimens (Freeman 2004; Landen 2007; Miner 2002; Wikander 1998) as well as a placebo group.

The following studies included a placebo run-in period: Cohen 2002; Cohen 2004; Freeman 2004; Glaxo 1996; Glaxo 1996a; Halbreich 1997; Halbreich 2002; Miner 2002; Pearlstein 1997; Pearlstein 2005; Steiner 1995; Steiner 2005; Stone 1991; Yonkers 1997.

 

Review outcomes reported in the included studies

 

Primary review outcomes

 
1. Overall premenstrual symptoms

The following 15 studies reported total self-rated symptom scores in a form that allowed pooling of the data: Cohen 2002; Cohen 2004; Eriksson 2008; Freeman 1999; Freeman 2004; Halbreich 2002; Jermain 1999; Kornstein 2006; Miner 2002; Ozeren 1997; Steiner 1995; Steiner 2005; Yonkers 1997. These studies utilised a range of self-rated tools, which are identified by footnotes in the forest plots.

Three other studies reported self-reported total symptom scores in a form that did not allow pooling of the data (Eriksson 2008; Freeman 2010; Glaxo 1996)

 
2. Adverse effects

Sixteen studies reported withdrawals due to adverse events in a form that allowed pooling of the data (Cohen 2002; Cohen 2004; Eriksson 1995; Eriksson 2008; Glaxo 2001; Halbreich 2002; Landen 2007; Ozeren 1997; Pearlstein 2005; Steiner 1995; Steiner 2005; Steiner 2008; Yonkers 1997).

The following 17 studies reported individual adverse effects in a form that allowed pooling of the data: Cohen 2002; Cohen 2004; Eriksson 1995; Eriksson 2008; Freeman 1999; Glaxo 1996a; Glaxo 2001; Halbreich 2002; Kornstein 2006; Landen 2007; Miner 2002; Pearlstein 1997; Pearlstein 2005; Steiner 1995; Steiner 2005; Steiner 2008; Stone 1991.

 

Secondary review outcomes

 
3. Specific symptoms of PMS

A wide variety of symptom measurement tools were used by the included studies, please see  Table 2.

3.1 Psychological symptoms

Ten studies reported psychological symptoms of PMS in a form that allowed pooling of the data (Arrendondo 1997; Cohen 2002; Freeman 1999; Glaxo 2001; Kornstein 2006; Miner 2002; Pearlstein 2005; Steiner 2005; Yonkers 1997).

3.2 Physical symptoms

Eleven studies reported physical symptoms of PMS in a form that allowed pooling of the data (Cohen 2002; Freeman 1999; Glaxo 2001; Halbreich 2002; Kornstein 2006; Miner 2002; Pearlstein 1997; Steiner 1995; Yonkers 1997).

3.3 Functional symptoms

Five studies reported functional symptoms of PMS in a form that allowed pooling of the data (Cohen 2002; Eriksson 2008; Kornstein 2006; Miner 2002; Yonkers 1997).

3.4 Irritability

Eight studies reported irritability in a form that allowed pooling of the data (Cohen 2002; Freeman 1999; Halbreich 2002; Pearlstein 1997; Steiner 2008; Yonkers 1997).

 
4. Response

Twenty-one studies reported response rates in a form that allowed pooling of the data (Cohen 2004; Crnobaric 1998; Eriksson 1995; Eriksson 2008; Freeman 1999; Freeman 2004; Glaxo 1996; Glaxo 2001; Halbreich 2002; Kornstein 2006; Landen 2007; Ozeren 1997; Pearlstein 1997; Pearlstein 2005; Steiner 1995; Steiner 2005; Stone 1991; Wikander 1998; Yonkers 1997). The definition of response varied across studies and is defined in footnotes in the forest plots.

 
5. Withdrawal for any reason

Fourteen studies reported overall withdrawal rates in a form that allowed pooling of the data (Crnobaric 1998; Eriksson 2008; Freeman 1999; Glaxo 1996; Glaxo 2001; Halbreich 2002; Jermain 1999; Ozeren 1997; Steiner 2008; Stone 1991; Yonkers 1997).

For details please see  Table 2 and Characteristics of included studies.

 

Excluded studies

Twenty-six studies were excluded (see Characteristics of excluded studies), in most cases because they were not properly randomised, were unblinded, were not placebo controlled or did not report the comparison of interest.

 

Risk of bias in included studies

Summaries of the risk of bias assessment are given in Figure 2 and Figure 3.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
 FigureFigure 3. Risk of bias summary: review authors' judgments about each risk of bias item for each included study.

 

Allocation

 

Sequence generation

Eleven studies described adequate methods of randomisation and were rated as at low risk of bias related to sequence generation (Cohen 2002; Cohen 2004; Eriksson 2008; Freeman 1999; Freeman 2004; Halbreich 2002; Landen 2007; Miner 2002; Pearlstein 2005; Steiner 2008; Yonkers 1997). The other 20 studies did not clearly describe their methods and were rated as at unclear risk of bias.

 

Allocation concealment

Four studies described adequate methods of allocation concealment and were rated as at low risk of bias in this domain (Eriksson 2008; Freeman 1999; Freeman 2004; Yonkers 1997). The other 27 studies did not clearly describe their methods and were rated as at unclear risk of bias.

 

Blinding

Eleven studies reported details of double blinding and were rated as at low risk of bias in this domain (Cohen 2002; Cohen 2004; Eriksson 1995; Eriksson 2008; Freeman 1999; Freeman 2004; Freeman 2010; Menkes 1992; Pearlstein 1997; Su 1997; Young 1998). The other 20 studies were described as double blinded but provided no further details and were rated as at unclear risk of bias.

 

Incomplete outcome data

Fourteen studies analysed all or most women by intention to treat, and were rated as at low risk of attrition bias (Cohen 2002; Crnobaric 1998; Eriksson 2008; Glaxo 2001; Landen 2007; Miner 2002; Pearlstein 1997; Pearlstein 2005; Steiner 2005; Steiner 2008; Stone 1991; Su 1997; Wood 1992; Yonkers 1997). Four studies had data missing for over 20% of participants and were rated as at high risk of attrition bias (Halbreich 1997; Jermain 1999; Kornstein 2006; Young 1998). The other 13 studies were at unclear risk of attrition bias due to unclear reporting of numbers randomised or numbers analysed, or failure to include 10% to 20% of participants in the analysis. A number of these studies also imputed a high proportion of data.

 

Selective reporting

Three studies were rated as at low risk of this bias (Eriksson 1995; Landen 2007; Wikander 1998). These studies prospectively collected data on adverse effects and no potential source of selective reporting bias was identified. Three studies were rated as at high risk of this bias. These studies collected data for efficacy and adverse effects that were not fully reported or not published (Freeman 2010; Glaxo 1996a; Steiner 2008). The other 25 studies were rated as at unclear risk of selective reporting bias. Most of these studies collected data on adverse events retrospectively (often by spontaneous participant report) or did not report adverse events data in an extractable form for either comparison group.

 

Other potential sources of bias

No other potential source of bias was identified in seven studies, and these studies were rated as at low risk for this domain (Eriksson 1995; Eriksson 2008; Freeman 1999; Glaxo 2001; Ozeren 1997; Su 1997; Young 1998). The other 24 studies were rated as at unclear risk of other potential bias, in most cases because they excluded placebo responders from the study, were crossover studies (for which only first-phase data were included in this review), or very few details were reported about the study design.

 

Effects of interventions

See:  Summary of findings for the main comparison SSRIs for premenstrual syndrome: all symptoms (end scores);  Summary of findings 2 SSRIs for premenstrual syndrome: all symptoms (change scores);  Summary of findings 3 SSRIs for premenstrual syndrome: withdrawal due to adverse effects

 

Primary outcomes

 

1. Total symptoms

Fifteen studies reported total self-rated symptom scores. Nine studies reported end scores for this outcome (Cohen 2004; Eriksson 2008; Freeman 1999; Freeman 2004; Halbreich 2002; Jermain 1999; Ozeren 1997; Steiner 1995; Yonkers 1997), four only reported change scores (Cohen 2002; Kornstein 2006; Miner 2002; Steiner 2005) and one reported only descriptive data (Glaxo 1996).

 
1.1. Total symptoms: end scores

When effects were assessed with end scores, SSRIs reduced overall symptoms significantly more effectively than placebo, with a moderate effect size. This applied to low dose SSRIs (SMD - 0.67, 95% CI -0.29 to -1.05, two studies, 301 women; I2 = 59%;  Analysis 1.1), moderate dose SSRIs (SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; I2 = 58%;  Analysis 1.2, Figure 4) and high dose SSRIs (SMD -0.95, 95% CI - 0.58 to -1.31, one study, 134 women;  Analysis 1.3). There was substantial heterogeneity for both pooled analyses.

 FigureFigure 4. Forest plot of comparison: 1 SSRIs versus placebo - all symptoms (end scores), outcome: 1.2 Moderate dose SSRI.

The analyses were stratified by type of intervention (luteal or continuous). The effects of the intervention were non-significantly higher in the studies of continuous SSRIs, but there may have been too few studies in each group to show a significant difference.

Five of the studies in this analysis used sertraline. When analysis was restricted to these studies, there was a significant benefit for the SSRI group with a smaller effect size and no heterogeneity (SMD 0.46, 95% CI -0.32 to -0.60, five studies, 780 women; I2 = 0%). The other studies in this analysis used three different types of SSRI and there were too few using the same type to permit subgrouping.

 
1.2 Total symptoms: change scores

Similarly, when effects were assessed with change scores, SSRIs reduced overall symptoms significantly more effectively than placebo. However, the effect sizes were small. This applied to both low dose SSRIs (SMD -0.23, 95% CI -0.05 to -0.41, four studies, 677 women; I2 = 29%;  Analysis 2.1) and moderate dose SSRIs (SMD - 0.36, 95% CI -0.20 to -0.51, four studies, 657 women; I2 = 0%;  Analysis 2.2, Figure 5). Heterogeneity was low or absent.

 FigureFigure 5. Forest plot of comparison: 2 SSRIs versus placebo - all symptoms (change scores), outcome: 2.2 Moderate dose SSRI.

 
1.3 Total symptoms: descriptive data

Among studies reporting total self-assessed symptoms scores in a form that was not suitable for meta-analysis:

  • Eriksson 2008 reported that women taking escitalopram 10 mg or 20 mg had a significantly greater improvement in four key VAS symptoms than the placebo group;
  • Glaxo 1996, an unpublished study, reported no significant difference in luteal phase COPE score between paroxetine 20 mg and placebo;
  • Freeman 2010, an unpublished pilot study (n = 11), reported that women in both arms significantly improved from baseline, with no significant difference between the groups (which was attributed to lack of statistical power in this very small study). Penn Daily Symptom Report (DSR) scores decreased 41% in the drug arm and 28% in the placebo arm. 

 
1.4 Sensitivity analyses

  • Quality: restricting analysis to the few studies that were at low risk of selection bias (Eriksson 2008; Freeman 1999; Freeman 2004; Yonkers 1997) did not materially change the main findings with regard to total symptom control.
  • Statistical model: use of a fixed-effect model did not materially alter the main findings for the primary outcomes.

 

2. Adverse events

 
2.1 Withdrawals due to adverse events

Seventeen studies reported withdrawal from the study due to adverse events and reported results in a form that allowed pooling of the data. Women taking SSRIs were significantly more likely to withdraw from the study than women taking placebo. This applied to women taking low dose SSRIs (OR 1.76, 95% CI 1.13, to 2.75, seven studies, 1301 women; I2 = 0%), moderate dose SSRIs (OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; I2 = 0%;  Analysis 3.2, Figure 6) and high dose SSRIs (OR 6.35, 95% CI 2.88 to 14.00, one study;  Analysis 3.3). Heterogeneity was absent for these analyses (I2 = 0%).

 FigureFigure 6. Forest plot of comparison: 4 SSRIs versus placebo: withdrawal due to adverse events, outcome: 4.2 Mod dose.

 
2.2 Individual adverse events

Sixteen studies reported one or more individual adverse events in a form that allowed pooling of the data.

Compared to the placebo group, the SSRI group had higher rates of the following events.

  • Nausea (OR 3.43, 95% 2.63 to 4.47, 16 studies, 3385 women; I2 = 0%;  Analysis 4.1); NNH for moderate dose of 7.
  • Insomnia or sleep disturbance (OR 1.84, 95% CI 1.36 to 2.47, 16 studies, 3388 women; I2 = 0%;  Analysis 4.2); NNH for moderate dose of 25.
  • Sexual dysfunction or decreased libido (OR 2.26, 95% CI 1.54 to 3.31, 14 studies, 2847 women; I2 = 0%;  Analysis 4.3); NNH for moderate dose of 14.
  • Fatigue or sedation (OR 1.66, 95% CI 1.09 to 2.53, eight studies, 951 women; I2 = 0%;  Analysis 4.4); NNH for moderate dose of 14.
  • Dizziness or vertigo (OR 1.96, 95% CI 1.32 to 2.89, 11 studies, 2354 women; I2 = 0%;  Analysis 4.5); NNH for moderate dose of 25.
  • Tremor (OR 5.38, 95% CI 2.20 to 13.16, four studies, 1352 women; I2 = 0%;  Analysis 4.6); NNH for moderate dose of 20.
  • Somnolence and decreased concentration (OR 4.94, 95% CI 2.82 to 8.63, seven studies, 1797 women; I2 = 0%;  Analysis 4.7); NNH for moderate dose of 13.
  • Sweating (OR 3.02, 95% CI 1.79 to 5.11, nine studies, 2051 women; I2 = 0%;  Analysis 4.8); NNH for moderate dose of 14.
  • Dry mouth (OR 2.70, 95% CI 1.656 to 4.41, nine studies, 1474 women; I2 = 0%;  Analysis 4.9); NNH for moderate dose of 17.
  • Yawning (OR 4.24, 95% CI 1.63 to 10.99, five studies, 975 women; I2 = 0%;  Analysis 4.10); NNH for moderate dose of 14.
  • Asthenia or decreased energy (OR 3.28, 95% CI 2.16 to 4.98, seven studies, 1704 women; I2 = 0%;  Analysis 4.11); NNH for moderate dose of 9.
  • Diarrhoea (OR 2.21, 95% CI 1.35 to 3.62, 10 studies, 2402 women; I2 = 0%;  Analysis 4.12); NNH for moderate dose of 25.
  • Constipation (OR 2.35, 95% CI 1.04 to 5.29, six studies, 996 women; I2 = 0%;  Analysis 4.13); NNH for moderate dose of 33.

For most of these outcomes, inspection of the forest plots showed a clear dose-response trend, with an increased risk of adverse events in women receiving a higher dose of SSRI.

Rates of the following events did not differ between the two groups.

  • Gastrointestinal irritability or dyspepsia (OR 2.03, 95% CI 0.78 to 5.31, five studies, 803 women; I2 = 0%;  Analysis 4.14).
  • Headache (OR 1.13, 95% CI 0.89 to 1.42, 15 studies, 2866 women; I2 = 0%;  Analysis 4.15).
  • Decreased appetite (OR 1.77, 95% CI 0.79 to 3.98, three studies, 433 women; I2 = 0%;  Analysis 4.16).
  • Increased appetite (OR 1.36, 95% CI 0.34 to 5.46, three studies, 495 women; I2 = 0%;  Analysis 4.17).
  • Anxiety (OR 1.17, 95% CI 0.45 to 302, three studies, 397 women; I2 = 0%;  Analysis 4.18).
  • Cardiovascular symptoms (OR 3.94, 95% CI 0.89 to 17.39, three studies, 380 women; I2 = 0%;  Analysis 4.19).
  • Respiratory disorder (OR 0.70, 95% CI 0.46 to 1.06, four studies, 1334 women; I2 = 0%;  Analysis 4.20).
  • Sinusitis (OR 0.65, 95% CI 0.38 to 1.12, five studies, 1657 women; I2 = 0%;  Analysis 4.21).
  • Infection (OR 1.01, 95% CI 0.60 to 1.70, four studies, 1339 women; I2 = 4%;  Analysis 4.22).

Overall, heterogeneity was absent or minimal for analyses of adverse events (I2 = 0% to 4%).

Other side effects mentioned in one or more studies were breast tenderness (Stone 1991), numbness (Eriksson 1995), rash (Pearlstein 1997), trauma (Cohen 2004), vomiting (Pearlstein 2005), genital disorders (Pearlstein 2005), flu syndrome (Cohen 2004; Steiner 2008), back pain (Cohen 2002; Steiner 2008), pharyngitis and rhinitis (Cohen 2002), visual disturbance (Eriksson 1995; Steiner 1995), pain (Cohen 2002; Miner 2002), accidental injury (Cohen 2002) and abdominal pain (Glaxo 1996a). There was no significant difference between the groups for any of these outcomes, and the reported event rates were very low.

 

Secondary outcomes

 

3. Specific symptoms of PMS

 
3.1 Psychological symptoms

Eleven studies reported psychological symptom scores, either as end scores (five studies) or as change scores (four studies).

When psychological symptoms were assessed with end scores, SSRIs reduced symptoms significantly more effectively than placebo. Low dose SSRIs were associated with a small effect size (SMD -0.38, 95% CI -20.0 to -0.57, three studies, 470 women; I2 = 0%;  Analysis 5.1) and moderate dose SSRIs with a moderate effect size (SMD -0.51, 95% CI -0.37 to -0.65, five studies, 795 women; I2 = 0%;  Analysis 5.2 ). This applied to both luteal and continuous administration. Heterogeneity was absent.

When psychological symptoms were assessed with change scores, SSRIs reduced symptoms significantly more effectively than placebo, with a small effect size. This applied to both low dose SSRIs (SMD -0.26, 95% CI -0.11 to -0.42, four studies, 683 women; I2 = 5%;  Analysis 6.1) and moderate dose SSRIs (SMD -0.30, 95% CI -0.11 to -0.48, four studies, 681 women; I2 = 32%;  Analysis 6.2). There were few studies in this analysis, and findings were not significant when studies of luteal administration were considered separately. Overall, statistical heterogeneity was low to moderate.

 
3.2 Physical symptoms

Nine studies reported physical symptom scores, either as end scores (five studies) or as change scores (four studies).

When physical symptoms were assessed with end scores, there were no data for low dose SSRIs. Moderate dose SSRIs reduced physical symptoms significantly more than placebo, with a small effect size and moderate heterogeneity (SMD -0.43, 95% CI -0.21 to -0.65, five studies, 781 women; I2 = 50%;  Analysis 7.1). The heterogeneity was attributable to differences in type of administration. In the single study of luteal administration there was no significant difference between moderate dose SSRIs and placebo for this outcome (OR -0.13, 95% CI -0.40 to 0.13, one study, 219 women), while in the studies of continuous administration there was a significant benefit for the SSRI group, of moderate effect size (OR -0.52, 95% CI -0.69 to -0.3, four studies, 562 women; I2 = 0%). High dose SSRIs were associated with a moderate effect size (SMD -0.56, 95% CI -0.26 to -0.86, one study, 179 women;  Analysis 7.2).

When physical symptoms were assessed with change scores, SSRIs reduced symptoms significantly more effectively than placebo, with a small effect size. This applied to both low dose SSRIs (SMD -0.17, 95% CI -0.03 to -0.31, four studies, 752 women; I2 = 0%;  Analysis 8.1) and moderate dose SSRIs (SMD -0.27, 95% CI -0.10 to -0.44, four studies, 742 women; I2 = 27%;  Analysis 8.2). When the results were reported by type of administration, findings were no longer statistically significant except for moderate dose luteal administration. Overall, heterogeneity was absent or low.

 
3.3 Functional symptoms

Five studies reported functional symptom scores, reported either as end scores (two studies) or as change scores (three studies).

When functional symptoms were assessed with end scores, no significant difference was found between SSRIs and placebo for low dose SSRIs (SMD -0.34, 95% CI 0.05 to -0.74, one study, 100 women;  Analysis 9.1). Moderate dose SSRIs were associated with significantly reduced functional symptoms, with a moderate effect size (SMD -0.71, 95% CI -0.49 to -0.93, two studies, 334 women; I2 = 0%;  Analysis 9.2).

When functional symptoms were assessed with change scores, low dose SSRIs were of significant benefit compared to placebo, with a small effect size (SMD -0.22, 95% CI -0.05 to -0.40, three studies, 514 women; I2 = 0%;  Analysis 10.1). There was no significant difference between moderate dose SSRIs and placebo for this outcome (SMD -0.13, 95% CI 0.11 to -0.37, three studies, 467 women; I2 = 40%;  Analysis 10.2). Heterogeneity was absent for the analysis of low dose SSRIs, and moderate for the analysis of moderate dose SSRIs.

 
3.4 Irritability

Eight studies reported irritability scores, reported either as end scores (seven studies) or as change scores (one study).

When irritability was assessed with end scores, SSRIs reduced symptoms significantly more than placebo, with a moderate effect size. This applied to both low dose SSRIs (SMD -0.57, 95% CI -0.02 to -0.57, one study, 53 women;  Analysis 11.1) and moderate dose SSRIs (SMD -0.56, 95% CI -0.40 to -0.72, five studies, 655 women; I2 = 0%;  Analysis 11.2). Heterogeneity was absent.

Similarly, when irritability was assessed with change scores, SSRIs reduced symptoms significantly more than placebo. Low dose SSRIs were associated with a small effect size (SMD -0.39, 95% CI -0.09 to -0.70, one study, 169 women;  Analysis 12.1) and moderate dose SSRIs were associated with a moderate effect size (SMD -0.50, 95% CI -0.19 to -0.80, one study, 169 women;  Analysis 12.2).

 

4. Response rates

Nineteen studies reported response rates.

A treatment response was significantly more likely in women taking SSRIs than in those taking placebo. This applied to low dose SSRIs (OR 1.78, 95% CI 1.41 to 2.25, six studies, 1243 women; I2 = 0%;  Analysis 13.1), moderate dose SSRIs (OR 2.75, 95% CI 2.20 to 3.44, 19 studies, 2647 women; I2 = 33%;  Analysis 13.2) and high dose SSRIs (OR 3.44, 95% CI 1.86 to 6.34, one study, 211 women;  Analysis 13.3). Heterogeneity was absent or fairly low. The response rate was relatively low in the single study of semi-intermittent administration (Wikander 1998) (OR 1.50, 95% CI 0.24 to 9.38, one study, 40 women).

 

5. Study withdrawal for any reason

Twelve studies reported this outcome.

There was no significant difference between the SSRI and placebo groups in the overall study withdrawal rate. This applied both to low dose SSRIs (OR 1.03, 95% CI 0.45 to 2.35, three studies, 385 women; I2 = 53%;  Analysis 14.1) and to moderate dose SSRIs (OR 0.97, 95% CI 0.73 to1.28, 12 studies, 1217 women; I2 = 0%;  Analysis 14.2). There was high heterogeneity for the analysis of low dose SSRIs, attributable to a high dropout rate in the placebo group in one study.

 

Subgroup analyses

 
1. Studies with no placebo run-in

Analysis was restricted to studies without a placebo run-in (Eriksson 2008; Freeman 1999; Jermain 1999; Ozeren 1997) for the primary outcome with the largest number of included studies ( Analysis 1.2). SSRIs were associated with a significant improvement in overall symptoms compared to placebo, with a large effect size (OR -0.82, 95% CI -0.43 to -1.21, four studies, 305 women; I2 = 59%). However, as in the main analysis there was substantial heterogeneity (I2 = 59%).

No studies directly compared a placebo run-in versus no placebo run-in.

 
2. Luteal versus continuous administration

Both luteal and continuous administration of SSRIs were effective in symptom reduction compared to placebo. Three studies (Freeman 2004; Landen 2007; Wikander 1998) compared luteal phase versus continuous administration.

 
Total symptom scores

There was no significant difference between the two groups in symptom end scores (-0.04, 95% CI -0.39 to 0.31, two studies, 128 women; I2 = 0%) or in response rate (OR 0.82, 95% CI 0.37 to 1.80, three studies, 269 women; I2 = 50%). There was moderate heterogeneity for the analysis of response rates, possibly due to use of differing definitions of response.

 
Adverse events

Only one study (Landen 2007) compared side effects in women using luteal phase versus continuous SSRIs. There was no significant difference between the two groups in overall adverse events nor in the most commonly reported events (nausea, fatigue, headache, and somnolence), but significantly fewer women taking luteal SSRIs reported decreased libido (OR 0.18, 95% CI 0.04 to 0.84, one study, 118 women;  Analysis 15.3).

 
3. Semi-intermittent versus luteal or continuous administration

Only one study (Wikander 1998) included a group receiving semi-intermittent SSRIs. This type of administration was compared with luteal and continuous regimens. Only 39 women were included in each of these comparisons. Total symptom scores were not reported in this study.

 
Withdrawal due to adverse events

There was no significant difference for this outcome between the semi-intermittent group and either the luteal group (OR 3.18, 95% CI 0.30 to 33.58, one study, 39 women) or the continuous group (OR 1.50, 95% CI 0.22 to 10.14, one study, 39 women) ( Analysis 16.2).

 
Response rate

The response rate was significantly lower in the semi-intermittent group than in the luteal group (OR 0.18, 95% CI 0.03 to 0.98, one study, 39 women) but did not differ significantly between the semi-intermittent and the continuous group (OR 0.69, 95% CI 0.19 to 2.59, one study, 39 women) ( Analysis 16.1).

 

Assessment of reporting bias

A funnel plot (Figure 7) was constructed for  Analysis 1.2, which was the primary efficacy outcome with the largest number of studies (n = 9). It was not suggestive of publication bias.

 FigureFigure 7. Funnel plot of comparison: 1 SSRIs versus placebo - all symptoms (end scores), outcome: 1.2 Moderate dose SSRI.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Summary of main results

 
Effectiveness of SSRIs

The findings of this review indicate that SSRIs are effective for reducing the symptoms of premenstrual syndrome (PMS). This applies both to overall symptoms and also to specific types of symptom (that is psychological, physical, functional symptoms and irritability). Most of the data related to a moderate dose of SSRIs, taken either in the luteal phase only or continuously. Findings were fairly consistent regardless of the dose and timing of the SSRIs. Effect sizes were small or moderate for most outcomes. All the SSRIs tested appeared effective.

There was consistent evidence that even low doses of SSRIs were effective, although moderate doses generally were associated with a larger effect size and a higher response rate.

 
Adverse events

A wide range of side effects were reported in women taking SSRIs. When numbers needed to harm (NNH) were calculated (that is the number of women who would need to take a drug in order for one women to be likely to experience an event over and above her underlying risk), the most common side effects associated with a moderate dose of SSRI were nausea (NNH = 7), asthenia (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14).

For most of these adverse events there was a clear dose-response trend, with an increased risk of adverse events in women receiving a higher dose of SSRI. Adverse events were very common in the only study that used a high dose of SSRI.

 
Effectiveness and adverse events associated with different types of administration
 
Effectiveness

Only three of the included studies compared different types of SSRI administration, and they included only 269 participants. No significant difference in effectiveness was found between luteal and continuous administration for most outcomes, though there was substantial heterogeneity for the analysis of response rates (I2 = 50%).

It has been suggested that intermittent SSRI administration may be as effective as continuous administration with respect to symptoms such as irritability and mood swings, but may be less effective for somatic symptoms (Eriksson 2008). Our analysis of end scores for physical symptoms ( Analysis 7.1) provides some indirect support for this suggestion. However, direct comparisons between administration regimes are required and currently there are insufficient data to draw any conclusions. This is an area that could be further explored.

 
Adverse effects

Only one study compared the rates of individual adverse effects associated with different types of administration, and the difference between luteal and continuous administration was significant only for decreased libido (favouring luteal administration). It seems likely that the risk of adverse effects will be minimised by use of the lowest effective dose and an intermittent dosing regimen.

 
Overall findings

Overall, these findings support the use of SSRIs as an effective and reasonably tolerable first line treatment for PMS.

 

Overall completeness and applicability of evidence

The review included 31 studies and the findings were generally consistent with regard to both efficacy and safety outcomes. There was very little direct evidence about the relative effectiveness and tolerability of luteal versus continuous drug regimens.

There was some indication that heterogeneity for the primary outcome might relate to differences in effectiveness between SSRI types. However, there were too few studies of specific SSRIs to determine whether any particular SSRI appeared substantially more effective than any other, and subgroup analyses require very cautious interpretation. Direct head-to-head comparisons of different SSRIs would help determine their relative effectiveness and we propose that future updates of this review include such comparisons.

Several of the trials included in this analysis had a single-blind placebo run-in stage to exclude placebo responders, and exclusion of placebo responders may yield estimates of effect that differ from findings in an unselected population. A subgroup analysis of studies without placebo run-in protocols was carried out, which found a large effect size in the SSRI group, suggesting that the benefit of SSRIs may be stronger in an unselected population than in placebo responders. However subgroup findings require very cautious interpretation and, moreover, there was substantial heterogeneity for this analysis (I2 = 59%).

Studies have reported a high risk of relapse following cessation of treatment (Freeman 2009; Pearlstein 1994; Sundblad 1997). The risk appears to be highest in women with severe symptoms at baseline and in those who do not achieve remission, and it has been suggested that these factors be considered when determining the optimum duration of treatment (Freeman 2009).

 

Quality of the evidence

Overall, the study quality was poor, with only four studies reporting acceptable methods of randomisation and allocation concealment and nine studies at high risk of either attrition bias or selective reporting bias. For most studies the risk of bias was unclear, largely due to poor reporting of methods. The overall quality of the evidence for the main findings was graded as low to moderate using the GRADE criteria, due to the suboptimal quality of most of the included studies and moderate heterogeneity (I2 = 59%) in one of the primary analyses ( Analysis 1.2). See  Summary of findings for the main comparison;  Summary of findings 2;  Summary of findings 3.

 

Potential biases in the review process

Efforts were made to retrieve all eligible studies. However, it is likely that some unpublished studies were not retrieved. This is mainly because efforts to contact pharmaceutical companies, in 2013, were unsuccessful in most cases; automated responses were received but no information was sent. GlaxoSmithKline have recently undertaken to make unpublished data available (Glaxo 2012), and hence we were able to add to this review three unpublished studies on paroxetine dating from 1996. This raises the possibility that there may be other unpublished data that we are unable to access.

The choice of end scores (where reported) rather than change scores had the potential to influence effect estimates for the primary outcome. We considered including an additional analysis pooling all studies that reported change scores for the primary outcome, but we found that this allowed only two additional studies to be included in the analysis of change scores for moderate dose SSRIs. Other studies did not report effect estimates in a form which permitted the standard deviations of the change score to be extracted or calculated.

 

Agreements and disagreements with other studies or reviews

A systematic review of behavioural and pharmacological interventions for PMS (Kleinstauber 2012) included 14 RCTs of SSRIs versus no treatment, wait list or placebo, and found that SSRIs were associated with a small to moderate benefit for PMS symptoms. Similarly, an earlier systematic review (Halbreich 2008), which included 14 placebo-controlled RCTs of SSRIs for PMS, concluded that even though SSRIs are effective for many women with PMDD, alternative targeted treatments need to be developed since around 40% of women fail to respond to SSRIs.

A systematic review of 19 RCTs (Shah 2008) also found SSRIs effective for treating PMS and PMDD compared to placebo (OR 0.40, 95% 0.31 to 0.51), with substantial heterogeneity (I2 = 66%). In subgroup analysis, luteal dosing was found to be less effective than continuous administration (OR 0.55, 95% CI 0.45 to 0.68; OR 0.28, 95% CI 0.18 to 0.42, respectively).

The current review found no convincing evidence of a significant difference in effectiveness between luteal and continuous dosing ( Analysis 15.1;  Analysis 15.2). The difference in findings between the current review and Shah 2008 may possibly be due to differences in data management. In Shah 2008, with the exception of Veeninga 1990 (which was excluded from the current review), the three studies with the lowest effect estimates were studies of luteal phase SSRIs in which change scores had been converted to end scores by the review authors. In the current review, a) studies reporting end scores tended to report higher effect estimates than those reporting change scores, b) all studies of continuous administration reported end scores, and c) studies reporting end scores were not pooled with those reporting change scores.

A small (n = 36) open-label RCT (Wu 2008) comparing intermittent versus continuous paroxetine found that luteal and continuous administration were both effective for treating symptoms of PMDD. Effects were maintained over six months of follow-up and did not differ significantly between the groups. This study was not included in the current review because there was no placebo group.

As the authors of Shah 2008 suggest, more head-to-head trials of luteal versus continuous dosing strategies are needed to provide conclusive evidence on this point. Such studies should report both effectiveness and adverse effects.

A subgroup analysis by type of SSRI in Shah 2008 found no significant difference in effectiveness between the most commonly used SSRIs (citalopram, fluoxetine, paroxetine and sertraline).

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

 

Implications for practice

There is now very convincing evidence to support the use of SSRIs for reducing the symptoms of PMS. All doses appear effective, but there is a dose-response effect that applies both to symptom reduction and to adverse events. High doses of SSRIs may be intolerable. This review suggests that both intermittent and continuous dosing regimens are effective in reducing symptoms.

In most instances the choice of SSRI dose and type of administration could be based on an individual woman's preference and modified according to the effectiveness and tolerability of the chosen regimen.

 
Implications for research

Future research should focus on direct comparisons between different SSRI administration regimens, including their safety, tolerability and effectiveness for overall symptoms and for specific symptom types over long-term follow-up. Head-to-head comparisons of the effectiveness and tolerability of different SSRIs may also be useful, and such comparisons should be included in future updates of this review. A multiple treatment meta-analysis (network meta analysis or mixed treatment comparisons) should also be considered for this topic. Primary studies should report full statistical information with standard deviations for all continuous outcomes to facilitate their inclusion in meta-analysis.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

This review first appeared in the Lancet (Lancet 2000;356:1131-6). The Lancet version includes more RCTs, partly because the Cochrane statistical reviewers excluded five RCTs of crossover design from the meta-analysis of this review. The authors would like to acknowledge the contribution of K Wyatt and P Dimmock who were involved in the original review.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
Download statistical data

 
Comparison 1. SSRIs versus placebo - all symptoms (end scores)

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

 1 Low dose SSRI2301Std. Mean Difference (IV, Random, 95% CI)-0.67 [-1.05, -0.29]

    1.1 Luteal administration
1100Std. Mean Difference (IV, Random, 95% CI)-0.45 [-0.85, -0.05]

    1.2 Continuous administration
1201Std. Mean Difference (IV, Random, 95% CI)-0.84 [-1.13, -0.55]

 2 Moderate dose SSRI91276Std. Mean Difference (IV, Random, 95% CI)-0.65 [-0.84, -0.46]

    2.1 Luteal administration
4457Std. Mean Difference (IV, Random, 95% CI)-0.51 [-0.71, -0.31]

    2.2 Continuous administration
6819Std. Mean Difference (IV, Random, 95% CI)-0.73 [-1.01, -0.46]

 3 High dose SSRI1138Std. Mean Difference (IV, Random, 95% CI)-0.95 [-1.31, -0.58]

    3.1 Continuous administration
1138Std. Mean Difference (IV, Random, 95% CI)-0.95 [-1.31, -0.58]

 
Comparison 2. SSRIs versus placebo - all symptoms (change scores)

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

 1 Low dose SSRI4677Std. Mean Difference (IV, Random, 95% CI)-0.23 [-0.41, -0.05]

    1.1 Luteal administration
4677Std. Mean Difference (IV, Random, 95% CI)-0.23 [-0.41, -0.05]

 2 Moderate dose SSRI4657Std. Mean Difference (IV, Random, 95% CI)-0.36 [-0.51, -0.20]

    2.1 Luteal administration
4657Std. Mean Difference (IV, Random, 95% CI)-0.36 [-0.51, -0.20]

 
Comparison 3. SSRIs versus placebo: withdrawal due to adverse effects

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

 1 Low dose71301Odds Ratio (M-H, Random, 95% CI)1.76 [1.13, 2.75]

    1.1 Luteal administration
4600Odds Ratio (M-H, Random, 95% CI)2.21 [1.05, 4.65]

    1.2 Continuous administration
3701Odds Ratio (M-H, Random, 95% CI)1.56 [0.90, 2.71]

 2 Mod dose152447Odds Ratio (M-H, Fixed, 95% CI)2.55 [1.84, 3.53]

    2.1 Luteal administration
81171Odds Ratio (M-H, Fixed, 95% CI)3.23 [1.82, 5.73]

    2.2 Continuous administration
91276Odds Ratio (M-H, Fixed, 95% CI)2.24 [1.50, 3.34]

 3 High dose1Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Continuous administration
1231Odds Ratio (M-H, Fixed, 95% CI)6.35 [2.88, 14.00]

 
Comparison 4. SSRIs versus placebo: adverse events

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

 1 Nausea163385Odds Ratio (M-H, Random, 95% CI)3.43 [2.63, 4.47]

    1.1 Low dose
81102Odds Ratio (M-H, Random, 95% CI)2.24 [1.38, 3.63]

    1.2 Mod dose
162124Odds Ratio (M-H, Random, 95% CI)4.14 [2.98, 5.75]

    1.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)3.78 [1.24, 11.51]

 2 Insomnia or sleep disturbance163388Odds Ratio (M-H, Random, 95% CI)1.84 [1.36, 2.47]

    2.1 Low dose
101252Odds Ratio (M-H, Random, 95% CI)2.51 [1.39, 4.54]

    2.2 Mod dose
151977Odds Ratio (M-H, Random, 95% CI)1.53 [1.03, 2.26]

    2.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)4.40 [1.45, 13.30]

 3 Sexual dysfunction or decreased libido142847Odds Ratio (M-H, Random, 95% CI)2.26 [1.54, 3.31]

    3.1 Low dose
81082Odds Ratio (M-H, Random, 95% CI)1.98 [1.02, 3.85]

    3.2 Mod dose
141765Odds Ratio (M-H, Random, 95% CI)2.46 [1.52, 3.99]

 4 Fatigue or sedation8951Odds Ratio (M-H, Random, 95% CI)1.66 [1.09, 2.53]

    4.1 Low dose
2126Odds Ratio (M-H, Random, 95% CI)1.55 [0.52, 4.56]

    4.2 Mod dose
8666Odds Ratio (M-H, Random, 95% CI)1.49 [0.91, 2.43]

    4.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)3.88 [1.10, 13.70]

 5 Dizziness or vertigo112354Odds Ratio (M-H, Random, 95% CI)1.96 [1.32, 2.89]

    5.1 Low dose
6824Odds Ratio (M-H, Random, 95% CI)1.46 [0.75, 2.85]

    5.2 Mod dose
111371Odds Ratio (M-H, Random, 95% CI)2.11 [1.29, 3.45]

    5.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)8.57 [1.10, 66.76]

 6 Tremor41352Odds Ratio (M-H, Random, 95% CI)5.38 [2.20, 13.16]

    6.1 Low dose
3521Odds Ratio (M-H, Random, 95% CI)3.38 [0.59, 19.36]

    6.2 Mod dose
4672Odds Ratio (M-H, Random, 95% CI)4.94 [1.47, 16.61]

    6.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)12.85 [1.68, 98.36]

 7 Somnolence/decreased concentration71797Odds Ratio (M-H, Random, 95% CI)4.94 [2.82, 8.63]

    7.1 Low dose
4587Odds Ratio (M-H, Random, 95% CI)4.41 [1.62, 12.03]

    7.2 Mod dose
71051Odds Ratio (M-H, Random, 95% CI)4.89 [2.40, 9.96]

    7.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)8.57 [1.10, 66.76]

 8 Sweating92051Odds Ratio (M-H, Random, 95% CI)3.02 [1.79, 5.11]

    8.1 Low dose
4628Odds Ratio (M-H, Random, 95% CI)3.08 [0.89, 10.73]

    8.2 Mod dose
91264Odds Ratio (M-H, Random, 95% CI)2.97 [1.59, 5.55]

    8.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)3.26 [0.70, 15.11]

 9 Dry mouth91474Odds Ratio (M-H, Random, 95% CI)2.70 [1.65, 4.41]

    9.1 Low dose
3275Odds Ratio (M-H, Random, 95% CI)3.08 [0.84, 11.23]

    9.2 Mod dose
91040Odds Ratio (M-H, Random, 95% CI)2.60 [1.47, 4.58]

    9.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)2.95 [0.63, 13.84]

 10 Yawning5975Odds Ratio (M-H, Random, 95% CI)4.24 [1.63, 10.99]

    10.1 Low dose
3303Odds Ratio (M-H, Random, 95% CI)3.00 [0.52, 17.41]

    10.2 Mod dose
5513Odds Ratio (M-H, Random, 95% CI)4.60 [1.34, 15.74]

    10.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)6.92 [0.38, 125.21]

 11 Asthenia/decreased energy71704Odds Ratio (M-H, Random, 95% CI)3.28 [2.16, 4.98]

    11.1 Low dose
6841Odds Ratio (M-H, Random, 95% CI)3.18 [1.73, 5.86]

    11.2 Mod dose
7863Odds Ratio (M-H, Random, 95% CI)3.36 [1.89, 5.97]

 12 Diarrhoea102402Odds Ratio (M-H, Random, 95% CI)2.21 [1.35, 3.62]

    12.1 Low dose
71003Odds Ratio (M-H, Random, 95% CI)2.24 [0.97, 5.21]

    12.2 Mod dose
101399Odds Ratio (M-H, Random, 95% CI)2.20 [1.20, 4.03]

 13 Constipation6996Odds Ratio (M-H, Random, 95% CI)2.35 [1.04, 5.29]

    13.1 Low dose
3406Odds Ratio (M-H, Random, 95% CI)2.18 [0.60, 7.95]

    13.2 Mod dose
6590Odds Ratio (M-H, Random, 95% CI)2.47 [0.87, 6.98]

 14 Gastrointestinal irritability or dyspepsia5803Odds Ratio (M-H, Random, 95% CI)2.03 [0.78, 5.31]

    14.1 Low dose
2279Odds Ratio (M-H, Random, 95% CI)1.69 [0.31, 9.26]

    14.2 Mod dose
5524Odds Ratio (M-H, Random, 95% CI)2.21 [0.67, 7.29]

 15 Headache152866Odds Ratio (M-H, Random, 95% CI)1.13 [0.89, 1.42]

    15.1 Low dose
81102Odds Ratio (M-H, Random, 95% CI)1.18 [0.80, 1.73]

    15.2 Mod dose
151764Odds Ratio (M-H, Random, 95% CI)1.10 [0.83, 1.46]

 16 Decreased appetite3433Odds Ratio (M-H, Random, 95% CI)1.77 [0.79, 3.98]

    16.1 Low dose
147Odds Ratio (M-H, Random, 95% CI)2.22 [0.23, 21.73]

    16.2 Mod dose
3227Odds Ratio (M-H, Random, 95% CI)1.17 [0.36, 3.74]

    16.3 High dose
1159Odds Ratio (M-H, Random, 95% CI)2.75 [0.76, 9.95]

 17 Increased appetite3495Odds Ratio (M-H, Random, 95% CI)1.36 [0.34, 5.46]

    17.1 Low dose
1182Odds Ratio (M-H, Random, 95% CI)2.45 [0.12, 51.81]

    17.2 Mod dose
3313Odds Ratio (M-H, Random, 95% CI)1.03 [0.17, 6.19]

 18 Anxiety3397Odds Ratio (M-H, Random, 95% CI)1.17 [0.45, 3.02]

    18.1 Low dose
1130Odds Ratio (M-H, Random, 95% CI)2.65 [0.30, 23.45]

    18.2 Mod dose
3267Odds Ratio (M-H, Random, 95% CI)0.97 [0.34, 2.77]

 19 Cardiovascular symptoms3380Odds Ratio (M-H, Random, 95% CI)3.94 [0.89, 17.39]

    19.1 Mod dose
3225Odds Ratio (M-H, Random, 95% CI)3.67 [0.66, 20.44]

    19.2 High dose
1155Odds Ratio (M-H, Random, 95% CI)4.89 [0.26, 92.53]

 20 Respiratory disorder41334Odds Ratio (M-H, Random, 95% CI)0.70 [0.46, 1.06]

    20.1 Low dose
4664Odds Ratio (M-H, Random, 95% CI)0.82 [0.46, 1.46]

    20.2 Mod dose
4670Odds Ratio (M-H, Random, 95% CI)0.59 [0.29, 1.19]

 21 Sinusitis51657Odds Ratio (M-H, Random, 95% CI)0.65 [0.38, 1.12]

    21.1 Low dose
5828Odds Ratio (M-H, Random, 95% CI)0.84 [0.34, 2.10]

    21.2 Mod dose
5829Odds Ratio (M-H, Random, 95% CI)0.48 [0.22, 1.06]

 22 Infection41339Odds Ratio (M-H, Random, 95% CI)1.01 [0.60, 1.70]

    22.1 Low dose
4677Odds Ratio (M-H, Random, 95% CI)0.84 [0.41, 1.73]

    22.2 Mod dose
4662Odds Ratio (M-H, Random, 95% CI)1.13 [0.46, 2.77]

 
Comparison 5. SSRIs versus placebo - psychological symptoms (end scores)

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

 1 Low dose SSRI3470Std. Mean Difference (IV, Random, 95% CI)-0.38 [-0.57, -0.20]

    1.1 Luteal administration
1210Std. Mean Difference (IV, Random, 95% CI)-0.36 [-0.63, -0.08]

    1.2 Continuous administration
2260Std. Mean Difference (IV, Random, 95% CI)-0.40 [-0.65, -0.16]

 2 Moderate dose SSRI5795Std. Mean Difference (IV, Random, 95% CI)-0.51 [-0.65, -0.37]

    2.1 Luteal administration
1198Std. Mean Difference (IV, Random, 95% CI)-0.60 [-0.88, -0.31]

    2.2 Continuous administration
4597Std. Mean Difference (IV, Random, 95% CI)-0.48 [-0.64, -0.32]

 
Comparison 6. SSRIs versus placebo - psychological symptoms (change scores)

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

 1 Low dose SSRI4683Std. Mean Difference (IV, Random, 95% CI)-0.26 [-0.42, -0.11]

    1.1 Luteal administration
3445Std. Mean Difference (IV, Random, 95% CI)-0.29 [-0.52, -0.07]

    1.2 Continuous administration
1238Std. Mean Difference (IV, Random, 95% CI)-0.20 [-0.45, 0.06]

 2 Moderate dose SSRI4681Std. Mean Difference (IV, Random, 95% CI)-0.30 [-0.48, -0.11]

    2.1 Luteal administration
3449Std. Mean Difference (IV, Random, 95% CI)-0.29 [-0.58, -0.01]

    2.2 Continuous administration
1232Std. Mean Difference (IV, Random, 95% CI)-0.31 [-0.57, -0.05]

 
Comparison 7. SSRIs versus placebo - physical symptoms (end scores)

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

 1 Moderate dose SSRI5781Std. Mean Difference (IV, Random, 95% CI)-0.43 [-0.65, -0.21]

    1.1 Luteal administration
1219Std. Mean Difference (IV, Random, 95% CI)-0.13 [-0.40, 0.13]

    1.2 Continuous administration
4562Std. Mean Difference (IV, Random, 95% CI)-0.52 [-0.69, -0.35]

 2 High dose SSRI1179Std. Mean Difference (IV, Random, 95% CI)-0.56 [-0.86, -0.26]

    2.1 Continuous administration
1179Std. Mean Difference (IV, Random, 95% CI)-0.56 [-0.86, -0.26]

 
Comparison 8. SSRIs versus placebo - physical symptoms (change scores)

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

 1 Low dose SSRI4752Std. Mean Difference (IV, Random, 95% CI)-0.17 [-0.31, -0.03]

    1.1 Luteal administration
3514Std. Mean Difference (IV, Random, 95% CI)-0.15 [-0.32, 0.02]

    1.2 Continuous administration
1238Std. Mean Difference (IV, Random, 95% CI)-0.22 [-0.47, 0.04]

 2 Moderate dose SSRI4742Std. Mean Difference (IV, Random, 95% CI)-0.27 [-0.44, -0.10]

    2.1 Luteal administration
3510Std. Mean Difference (IV, Random, 95% CI)-0.30 [-0.54, -0.06]

    2.2 Continuous administration
1232Std. Mean Difference (IV, Random, 95% CI)-0.21 [-0.47, 0.05]

 
Comparison 9. SSRIs versus placebo - functional symptoms (end scores)

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

 1 Low dose SSRI1100Std. Mean Difference (IV, Random, 95% CI)-0.34 [-0.74, 0.05]

    1.1 Luteal administration
1100Std. Mean Difference (IV, Random, 95% CI)-0.34 [-0.74, 0.05]

 2 Moderate dose SSRI2334Std. Mean Difference (IV, Random, 95% CI)-0.71 [-0.93, -0.49]

    2.1 Luteal administration
2334Std. Mean Difference (IV, Random, 95% CI)-0.71 [-0.93, -0.49]

 
Comparison 10. SSRIs versus placebo - functional symptoms (change scores)

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

 1 Low dose SSRI3514Std. Mean Difference (IV, Random, 95% CI)-0.22 [-0.40, -0.05]

    1.1 Luteal administration
3514Std. Mean Difference (IV, Random, 95% CI)-0.22 [-0.40, -0.05]

 2 Moderate dose SSRI3467Std. Mean Difference (IV, Random, 95% CI)-0.13 [-0.37, 0.11]

    2.1 Luteal administration
3467Std. Mean Difference (IV, Random, 95% CI)-0.13 [-0.37, 0.11]

 
Comparison 11. SSRIs versus placebo - irritability (end scores)

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

 1 Low dose SSRI153Std. Mean Difference (IV, Random, 95% CI)-0.57 [-1.12, -0.02]

    1.1 Luteal administration
153Std. Mean Difference (IV, Random, 95% CI)-0.57 [-1.12, -0.02]

 2 Moderate dose SSRI5655Std. Mean Difference (IV, Random, 95% CI)-0.56 [-0.72, -0.40]

    2.1 Luteal administration
2282Std. Mean Difference (IV, Random, 95% CI)-0.65 [-0.93, -0.36]

    2.2 Continuous administration
3373Std. Mean Difference (IV, Random, 95% CI)-0.51 [-0.73, -0.30]

 
Comparison 12. SSRIs versus placebo - irritability (change scores)

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

 1 Low dose SSRI1169Std. Mean Difference (IV, Random, 95% CI)-0.39 [-0.70, -0.09]

    1.1 Luteal administration
1169Std. Mean Difference (IV, Random, 95% CI)-0.39 [-0.70, -0.09]

 2 Moderate dose SSRI1169Std. Mean Difference (IV, Random, 95% CI)-0.50 [-0.80, -0.19]

    2.1 Luteal administration
1169Std. Mean Difference (IV, Random, 95% CI)-0.50 [-0.80, -0.19]

 
Comparison 13. SSRIs versus placebo: response rates

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

 1 Low dose SSRI61243Odds Ratio (M-H, Random, 95% CI)1.78 [1.41, 2.25]

    1.1 Luteal administration
3554Odds Ratio (M-H, Random, 95% CI)2.08 [1.46, 2.98]

    1.2 Continuous administration
3689Odds Ratio (M-H, Random, 95% CI)1.59 [1.18, 2.16]

 2 Moderate dose SSRI192647Odds Ratio (M-H, Random, 95% CI)2.75 [2.20, 3.44]

    2.1 Luteal administration
7964Odds Ratio (M-H, Random, 95% CI)2.36 [1.71, 3.25]

    2.2 Semi-intermittent administration
126Odds Ratio (M-H, Random, 95% CI)1.5 [0.24, 9.38]

    2.3 Continuous administration
151657Odds Ratio (M-H, Random, 95% CI)3.13 [2.29, 4.27]

 3 High dose SSRI1Odds Ratio (M-H, Random, 95% CI)Subtotals only

    3.1 Continuous administration
1211Odds Ratio (M-H, Random, 95% CI)3.44 [1.86, 6.34]

 
Comparison 14. SSRIs versus placebo: withdrawal for any reason

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

 1 Low dose3385Odds Ratio (M-H, Random, 95% CI)1.03 [0.45, 2.35]

    1.1 Luteal administration
2169Odds Ratio (M-H, Random, 95% CI)1.18 [0.21, 6.50]

    1.2 Continuous administration
1216Odds Ratio (M-H, Random, 95% CI)0.91 [0.49, 1.68]

 2 Mod dose121217Odds Ratio (M-H, Random, 95% CI)0.97 [0.73, 1.28]

    2.1 Luteal administration
6720Odds Ratio (M-H, Random, 95% CI)0.96 [0.66, 1.39]

    2.2 Continuous administration
6497Odds Ratio (M-H, Random, 95% CI)0.99 [0.65, 1.51]

 
Comparison 15. Luteal SSRI versus continuous SSRI

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

 1 All symptoms (end scores)2128Std. Mean Difference (IV, Random, 95% CI)-0.04 [-0.39, 0.31]

    1.1 Mod dose
2128Std. Mean Difference (IV, Random, 95% CI)-0.04 [-0.39, 0.31]

 2 Response rate3269Odds Ratio (M-H, Random, 95% CI)0.82 [0.37, 1.80]

    2.1 Mod dose
3269Odds Ratio (M-H, Random, 95% CI)0.82 [0.37, 1.80]

 3 Adverse effects1714Odds Ratio (M-H, Random, 95% CI)0.68 [0.42, 1.12]

    3.1 Any adverse effects
1119Odds Ratio (M-H, Random, 95% CI)0.46 [0.11, 1.95]

    3.2 Headache
1119Odds Ratio (M-H, Random, 95% CI)0.54 [0.22, 1.35]

    3.3 Nausea
1119Odds Ratio (M-H, Random, 95% CI)1.35 [0.66, 2.78]

    3.4 Fatigue
1119Odds Ratio (M-H, Random, 95% CI)0.91 [0.35, 2.34]

    3.5 Somnolence
1119Odds Ratio (M-H, Random, 95% CI)0.59 [0.23, 1.50]

    3.6 Decreased libido
1119Odds Ratio (M-H, Random, 95% CI)0.18 [0.04, 0.84]

 
Comparison 16. Semi-intermittent versus other regimens

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

 1 Response rate1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Semi-intermittent versus luteal
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Semi-intermittent versus continuous
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Withdrawal due to adverse effects1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 Semi-intermittent versus continuous
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Semi-intermittent versus luteal
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Appendix 1. MEDLINE search strategy

1 Premenstrual Syndrome/

2 premenstrua$.tw.

3 pre-menstrua$.tw.

4 late luteal.tw.

5 luteal phase.tw.

6 (luteal adj5 symptom$).tw.

7 (PMS or PMD or PMDD or LLPDD).tw.

8 or/1-7

9 exp serotonin uptake inhibitors/ or amoxapine/ or citalopram/ or clomipramine/ or fenfluramine/ or fluoxetine/ or fluvoxamine/ or norfenfluramine/ or paroxetine/ or sertraline/ or trazodone/ or zimeldine/

10 (serotonin adj5 inhibitor$).tw.

11 (amoxapine or citalopram or clomipramine or fenfluramine or fluoxetine or fluvoxamine or norfenfluramine or paroxetine or sertraline or trazodone or zimeldine).tw.

12 SSRI.tw.

13 (5-hydroxytryptamine adj5 inhibitor$).tw.

14 (5-ht adj5 inhibitor$).tw.

15 or/9-14

16 8 and 15

17 randomised controlled trial.pt.

18 controlled clinical trial.pt.

19 Randomized Controlled Trials/

20 Random allocation/

21 Double-blind method/

22 Single-blind method/

23 or/17-22

24 clinical trial.pt.

25 exp clinical trials/

26 (clin$ adj25 trial$).ti,ab,sh.

27 ((singl$ or doubl$ or tripl$ or trebl$) adj25 (blind$ or mask$)).ti,ab,sh.

28 Placebos/

29 placebo$.ti,ab,sh.

30 random$.ti,ab,sh.

31 Research design/

32 or/24-31

33 animal/ not (human/ and animal/)

34 23 or 32

35 34 not 33

36 16 and 35

37 (2002$ or 2003$ or 2004$ or 2005$ or 2006$ or 2007$ or 2008$).ed.

38 36 and 37

 

Appendix 2. EMBASE search strategy

1 premenstrua$.tw.
2 pre-menstrua$.tw.
3 late luteal.tw.
4 luteal phase.tw.
5 (luteal adj5 symptom$).tw.
6 (PMS or PMD or PMDD or LLPDD).tw.
7 premenstrual dysphoric disorder/ or premenstrual syndrome/
8 exp Serotonin Uptake Inhibitor/
9 (serotonin adj5 inhibitor$).tw.
10 (amoxapine or citalopram or clomipramine or fenfluramine or fluoxetine or fluvoxamine or norfenfluramine or paroxetine or sertraline or trazodone or zimeldine).tw.
11 SSRI.tw.
12 (5-hydroxytryptamine adj5 inhibitor$).tw.
13 (5-ht adj5 inhibitor$).tw.
14 or/1-7
15 or/8-13
16 14 and 15
17 Controlled study/ or randomized controlled trial/
18 double blind procedure/
19 single blind procedure/
20 crossover procedure/
21 drug comparison/
22 placebo/
23 random$.ti,ab,hw,tn,mf.
24 latin square.ti,ab,hw,tn,mf.
25 crossover.ti,ab,hw,tn,mf.
26 cross-over.ti,ab,hw,tn,mf.
27 placebo$.ti,ab,hw,tn,mf.
28 ((doubl$ or singl$ or tripl$ or trebl$) adj5 (blind$ or mask$)).ti,ab,hw,tn,mf.
29 (comparative adj5 trial$).ti,ab,hw,tn,mf.
30 (clinical adj5 trial$).ti,ab,hw,tn,mf.
31 or/17-30
32 nonhuman/
33 animal/ not (human/ and animal/)
34 or/32-33
35 31 not 34
36 16 and 35
37 (2012$ or 2013$).em.
38 36 and 37

 

Appendix 3. PsycINFO search strategy

atabase: PsycINFO <1806 to February Week 1 2013>

Search Strategy:

--------------------------------------------------------------------------------

1 exp Premenstrual Syndrome/

2 premenstrua$.tw.

3 pre-menstrua$.tw.

4 late luteal.tw.

5 luteal phase.tw.

6 (luteal adj5 symptom$).tw.

7 (PMS or PMD or PMDD or LLPDD).tw.

8 (Dysphoric adj2 disorder$).tw.

9 exp Premenstrual Dysphoric Disorder/

10 or/1-9

11 exp Serotonin Reuptake Inhibitors/ or exp Antidepressant Drugs/

12 exp Citalopram/

13 exp Chlorimipramine/

14 exp Fenfluramine/

15 exp Fluoxetine/

16 exp Fluvoxamine/

17 exp Paroxetine/

18 exp Sertraline/

19 exp Trazodone/

20 exp Zimeldine/

21 (serotonin adj5 inhibitor$).tw.

22 (amoxapine or citalopram or clomipramine or fenfluramine or fluoxetine or fluvoxamine or norfenfluramine or paroxetine or sertraline or trazodone or zimeldine).tw.

23 SSRI$.tw.

24 (5-hydroxytryptamine adj5 inhibitor$).tw.

25 (5-ht adj5 inhibitor$).tw.

26 or/11-25

27 10 and 26

28 random.tw.

29 control.tw.

30 double-blind.tw.

31 clinical trials/

32 placebo/

33 exp Treatment/

34 or/28-33

35 27 and 34

 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Last assessed as up-to-date: 11 February 2013.


DateEventDescription

23 May 2013New citation required but conclusions have not changedThe additional evidence did not change the conclusions of this review.

20 February 2013New search has been performedAdded six new studies: Eriksson 2008, Freeman 2010, Glaxo 1996, Glaxo 1996a, Glaxo 2001, Steiner 2008.

Some studies were split into multiple comparisons in earlier versions of the review, each with a separate study reference; such studies have been combined and referenced as a single study in this update.

Excluded three previously included studies: Sundblad 1992, Sundblad 1993, Veeninga 1990.



 

History

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Protocol first published: Issue 1, 1999
Review first published: Issue 4, 2002


DateEventDescription

11 February 2009New citation required but conclusions have not changedReview updated May 2008

4 May 2008New search has been performedNew studies identified and major update completed

31 March 2008AmendedConverted to new review format.

28 February 2002New citation required and conclusions have changedSubstantive amendment



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 
2013 update

Jane Marjoribanks (JM) led the 2013 update; performed searches; selected included and excluded trials; performed data extraction, quality assessment of trials and statistical analysis; drafted the text and incorporated changes suggested by other authors.

Katrina Wyatt (KW) checked the study selection and read the draft.

Shaughn O'Brien (SO) commented on the draft from a clinical perspective and suggested changes and additions.

Julie Brown (JB) checked the risk of bias assessment and data extraction.

 
Earlier versions of the review

JB took the lead in writing the 2009 update review, performed searches, selected included and excluded trials, performed data extraction, quality assessment of trials and statistical analysis, drafted the text and incorporated changes suggested by other authors. JM assisted in data extraction in the 2009 update. SO and KW commented on the review update

SO conceptualised the original review, commented on drafts of the protocol and the original review, and provided clinical interpretation of the data. He also assisted in providing comments on draft versions of the update. KW took the lead in writing the original protocol and review, performed initial searches for trials, was involved in selection of included trials, performed data extraction and quality assessment of trials, and assisted in statistical analysis and interpretation of the data. PWD assisted in writing the original protocol and review, contacted authors for additional information, was involved in selection of included trials, performed data extraction and quality assessment of trials, and conducted the statistical analysis and interpretation of the data.

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

Julie Brown and Jane Marjoribanks have no conflict of interest.

PMS O'Brien has been funded over many years for research personnel, consultancies, lectures and conferences by the following companies: Bayer Schering, Hoechst Marion Roussel Ltd, Shire Pharmaceuticals, Smith Kline Beecham, Eli Lilly, Searle, Sanofi Winthrop, Zeneca, Organon, Solvay Pharmaceuticals and Novo Nordisk.

KM Wyatt has no conflict of interest.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms
 

Internal sources

  • No source provided, Not specified.

 

External sources

  • None provided, Not specified.

 

Differences between protocol and review

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. History
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Differences between protocol and review
  18. Index terms

2013 update:

  • updated methods section to current Cochrane recommendations;
  • designated adverse events a primary outcome (previously a secondary outcome);
  • amalgamated each included study under a single study ID, with all references included (abstracts of included studies formally listed under excluded studies);
  • reformatted analyses by dose;
  • unpooled SMDs of change scores and end scores (because the Cochrane Handbook for Systematic Reviews of Interventions recommends that these are not pooled).

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract摘要Résumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Arrendondo 1997 {published data only}
  • Arredondo-Soberon F, Freeman EW, Sondheimer SJ. Relationship and response of food cravings and depression to sertraline in patients with premenstrual syndrome. Fertility and Sterility 1997;October:S28.
Cohen 2002 {published data only}
  • Cohen L, Miner C, Brown E, Dillon J. Efficacy of intermittent fluoxetine dosing in premenstrual dysphoric disorder (PMDD). European Neuropsychopharmacology 2001;11 Suppl 3:210.
  • Cohen L, Miner C, Brown E, Freeman E, Halbreich U, Sundell K, McCray S. Premenstrual daily fluoxetine for premenstrual dysphoric disorder: A placebo controlled, clinical trial using computerized diaries. Obstetrics and Gynecology 2002;100(3):435-44.
  • Cohen L, Soares C, Yonkers K, et al. Paroxetine controlled release (CR) is effective in the treatment of premenstrual dysphoric disorder (PMDD): Results from a randomized placebo controlled trial. 15th Annual US Psychiatric and Mental Health Congress. October 28- November 3rd. Las Vegas, Nevada. 2002:Abstract 39.
  • Judge R, Brown E, Miner C, Dillon J. Intermittent fluoxetine dosing in premenstrual dysphoric syndrome. World Journal of Biological Psychiatry 2001;2 Suppl:204.
  • Miner C, Cohen LS, O'Brien PMS, Davis S, Brown E, Jacobson J. Predictors of response to luteal phase fluoxetine treatment of PMDD. The International Journal of Neuropsychopharmacology 2002;5 Suppl:87.
Cohen 2004 {published data only}
  • Cohen L, Soares C, Yonkers K, Bellew K, Bridges I, Heller V. Paroxetine controlled release is effective in treating premenstrual dysphoric disorder. Obstetrics and Gynecology 2003;101 Suppl 4:111.
  • Cohen L, Soares C, Yonkers K, Bellew K, Bridges I, Steiner M. Paroxetine controlled release for premenstrual dysphoric disorder: A double blind, placebo controlled trial. Psychosomatic Medicine 2004;66:707-13.
  • GlaxoSmithKline. A Double-Blind, Placebo-Controlled, Three-Arm Fixed-Dose Study of Paroxetine CR Continuous Treatment (12.5 mg/day and 25 mg/day) for Premenstrual Dysphoric Disorder. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F677&studyId=3742A8A5-2C3C-4A40-B9B5-7975DF70CF53&compound=paroxetine Accessed 16 August 2012.
  • GlaxoSmithKline NZ. Phone call from a representative of GlaxoSmithKline New Zealand (in response to an email sent by J Marjoribanks) confirming that 29060/677 (Cohen 2004) and 29060/689 (Pearlstein 2005) were separate studies July 2012.
  • Pearlstein 2012. Email to Jane Marjoribanks from Teri Pearlstein advising that participants in Pearlstein 2005 and Cohen 2004 did not, to her knowledge, overlap. 22.6.12.
Crnobaric 1998 {published data only}
  • Crnobaric C, Jasovic-Gasic M, Milanovanic S, Miljevic C. Treatment of premenstrual dysphoric disorder with fluoxetine during the luteal phase. 9th Congress of the Association of European Psychiatrists. Copenhagen, Denmark, 20-24 September 1998.
Eriksson 1995 {published data only}
  • Eriksson E, Hedberg MA, Andersch B, Sunblad C. The serotonin reuptake inhibitor paroxetin is superior to the noradrenaline reuptake inhibitor maprotiline in the treatment of premenstrual syndrome. Neuropsychopharmacology 1995;12:167-76.
Eriksson 2008 {published data only}
  • Eriksson E, Ekman A, Sinclair S, Sorvik K, Ysandeer C, Mattson U-B, Nissbrandt H. Escitalopram administered in the luteal phase exerts a marked and dose-dependent effect in premenstrual dysphoric disorder. Journal of Clinical Psychopharmacology 2008;28(2):195-202.
Freeman 1999 {published data only}
Freeman 2004 {published data only}
  • Freeman E, Rickels K, Sondheimer S, Polansky M, Xiao S. Continuous or intermittent dosing with sertraline for patients with severe premenstrual syndrome or premenstrual dysphoric disorder. American Journal of Psychiatry 2004;161(2):343-51.
  • Freeman EW, Rickels K, Sammel MD, Lin H, Sondheimer SS. Time to relapse after short-term or long-term sertraline treatment for severe premenstrual syndromes. Archives of General Psychiatry 2009;66(5):537-44.
Freeman 2010 {unpublished data only}
  • Freeman E. Escitalopram for Premenstrual Syndrome (PMS) in Teens: A Pilot Study NCT00523705. http://clinicaltrials.gov/ct2/show/NCT00523705.
Glaxo 1996 {unpublished data only}
  • GlaxoSmithKline. A Double-Blind, Placebo Controlled Study to Investigate the Efficacy, Safety and Tolerability of Paroxetine in Patients with Premenstrual Dysphoric Disorder. [Study No PAR 29060.400]. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F400&studyId=80268FE4-8DB0-4A5A-8CF4-51162DA5EE83&compound=paroxetine Accessed 16 August 2012.
Glaxo 1996a {unpublished data only}
  • GlaxoSmithKline. A Multicentre, Double-Blind, Placebo-Controlled Study to Investigate the Effects of Paroxetine (5mg OD Vs 10mg OD Vs 20mg OD) in Patients with Premenstrual Dysphoric Disorder (PMDD) [Study No PAR 29060.427]. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F427&studyId=46B83DBA-A3AD-44FB-84F7-51BC66679F35&compound=paroxetine Accessed 16 August 2012.
Glaxo 2001 {unpublished data only}
  • GlaxoSmithKline. A Double-Blind, Placebo-Controlled, 3-Arm, Fixed-Dose Study of Paroxetine CR Continuous Treatment (12.5 mg/day and 25 mg/day) for Premenstrual Dysphoric Disorder [Study No 29060/688]. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F688&studyId=4EAE38F8-954D-453B-BA8C-32CA4FFAD277&compound=paroxetine Accessed 16 August 2012.
Halbreich 1997 {published data only}
Halbreich 2002 {published data only}
  • Halbreich U, Bergeron R, Freeman E, Stout A, Cohen L. Intermittent (luteal phase) dosing of sertraline effective in PMDD. International Journal of Neuropsychopharmacology 2000;3 Suppl 1:248.
  • Halbreich U, Bergeron R, Stout A, Freeman E, Yonkers K, Pearlstein T, et al. Dosing of sertraline is effective in premenstrual dysphoric disorder. 155th Annual Meeting of the American Psychiatric Association. 13th-18th May 2000.
  • Halbreich U, Bergeron R, Yonkers K, Freeman E, Stout A, Cohen L. Efficacy of intermittent, luteal phase sertraline treatment of premenstrual dysphoric disorder. Obstetrics and Gynecology 2002;100(6):1219-29.
  • Pearlstein T, Yonkers K, Fayyad R, Gillespie J. Pretreatment pattern of symptom expression in premenstrual dysphoric disorder. Journal of Affective Disorders 2005;85:275-82.
Jermain 1999 {published data only}
  • Jermain DM, Preece CK, Sykes RL, Kuehl TJ, Sulak PJ. Luteal phase sertraline for the treatment of premenstrual dysphoric disorder. Archives of Family Medicine 1999;8:328-32.
Kornstein 2006 {published data only}
  • Kornstein S, Gillespie J. Double blind placebo controlled study of sertraline in premenstrual syndrome. 155th Annual Meeting of the American Psychiatric Association. May 18-23, Philadelphia PA. 2002:NR248.
  • Kornstein S, Pearlstein T, Fayyad R, Farfel G, Gillespie J. Low dose sertraline in the treatment of moderate to severe premenstrual syndrome: Efficacy of 3 dosing strategies. Journal of Clinical Psychiatry 2006;67(10):1624-32.
Landen 2007 {published data only}
  • Bellew KM, Landen M, Hunter B, McCafferty JP. Social functioning improves with paroxetine treatment. 155th Annual Meeting of the American Psychiatric Association. May 18-23, Philadelphia. 2002:NR282.
  • GlaxoSmithKline. A Placebo-Controlled Study to Investigate the Efficacy of Intermittent and Continuous Treatment With Paroxetine in Patients With Premenstrual Dysphoric Disorder (PMDD). http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F658&studyId=186F6412-CDE1-4505-8ACD-FBB1858393EB&compound=paroxetine Accessed 16 August 2012.
  • Landen M, Sorvik K, Ysander C, Allgulander C, Nissbrandt H, Gezelius B, et al. A placebo controlled trial exploring the efficacy of paroxetine for the treatment of premenstrual dysphoria. American Psychiatric Association, 155th annual meeting. May 18-23. Philadelphia, PA., 2002.
  • Landen M, Ysander K, Sorvik K, Nissbrandt H, Allgulander C, Hunter B, et al. A placebo controlled study of the efficacy of intermittent and continuous treatment with paroxetine for premenstrual dysphoric disorder (PMDD). European Neuropsychopharmacology 2001;11 Suppl 3:308-9.
  • Landen MSG. A Placebo-Controlled Study to Investigate the Onset of Action of Paroxetine in Premenstrual Dysphoria. http://clinicaltrials.gov/ct2/show/NCT00516113 2007.
  • Länden M, Nissbrandt H, Allgulander C, Sorvik K, Ysander C, Eriksson E. Placebo controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder. Neuropsychopharmacology 2007;32:153-61.
Menkes 1992 {published data only}
  • Menkes DB, Taghavi E, Mason PA, Spears GF, Howard RC. Fluoxetine treatment of severe premenstrual syndrome. BMJ 1992;305(6489):346-7.
  • Menkes DB, Taghavi E, Mason PA, Spears GF, Howard RC. Fluoxetine treatment of severe premenstrual syndrome. International Clinical Psychopharmacology 1993;8:95-102.
Miner 2002 {published data only}
  • Miner C, Brown E, McCray S, Gonzales J, Wohlreich M. Weekly luteal phase dosing with enteric coated fluoxetine 90mg in premenstrual dysphoric disorder: A randomised, double blind, placebo controlled clinical study. Clinical Therapeutics 2002;24(3):417-33.
  • Miner C, Cohen LS, O'Brien PMS, Davis S, Brown E, Jacobson J. Predictors of response to luteal phase fluoxetine treatment of PMDD. The International Journal of Neuropsychopharmacology 2002;5 Suppl:87.
Ozeren 1997 {published data only}
Pearlstein 1997 {published data only}
  • Pearlstein TB, Stone AB, Lund SA, Scheft H, Zlotnick C, Brown WA. Comparison of fluoxetine, bupropion and placebo in the treatment of premenstrual dsyphoric disorder. Journal of Clinical Psychopharmacology 1997;17:261-6.
Pearlstein 2005 {published data only}
  • GlaxoSmithKline. A Double-Blind, Placebo-Controlled, 3-Arm, Fixed-Dose Study of Paroxetine CR Continuous Treatment (12.5 mg/day and 25 mg/day) for Premenstrual Dysphoric Disorder. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F689&studyId=6F9A5C75-99C3-4F11-AED7-A122263D1746&compound=paroxetine Accessed 16 August 2012.
  • GlaxoSmithKline NZ. Phone call from a representative of GlaxoSmithKline New Zealand (in response to an email sent by J. Marjoribanks) confirming that 29060/677 (Cohen 2004) and 29060/689 (Pearlstein 2005) were separate studies July 2012.
  • Pearlstein 2012. Email to Jane Marjoribanks from Teri Pearlstein advising that participants in Pearlstein 2005 and Cohen 2004 did not, to her knowledge, overlap. 22.6.12.
  • Pearlstein T, Bellew K, Endicott J, Steiner M. Paroxetine controlled release for premenstrual dysphoric disorder: remission analysis following a randomized, double blind, placebo controlled trial. 41st Annual Meeting of the American College of Neuropsychopharmacology (ACNP), San Juan, Puerto Rico. Dec 8-12 2002.
Steiner 1995 {published data only}
  • Dillon J, Steiner M, Judge R, Brown E. Fluoxetine improves social functioning in women with premenstrual dysphoria. International Journal of Gynecology and Obstetrics 2000;70 Suppl 3:99.
  • Koke S, Steiner M, Judge R, Babcock S, Dillon J. Efficacy of fluoxetine in improving mood symptoms and social impairments in patients with PMDD. Psychosomatics 2001;42(2):178.
  • Nilsson M Judge R, Brown E, Schuler C. Fluoxetine's efficacy in improving mood. physical and social impairment symptoms associated with PMDD. International Journal of Gynecology and Obstetrics 2000;Abstract Book 3:96.
  • Steiner M, Babcock S, McCray SD, Romano S. Fluoxetine's efficacy in improving premenstrual dysphoric disorder. 152nd Annual Meeting of the American Psychiatric Association, Washington DC. USA. 15-20th May 1999.
  • Steiner M, Babcock S, Steinberg SI, Stewart DE, Carter D, Berger C. Fluoxetine's efficacy in improving physical symptoms associated with pdd: results from a multisite, randomized placebo controlled trial. 152nd Annual Meeting of the American Psychiatric Association. Washington DC USA. 15-20 May 1999.
  • Steiner M, Brown E, Trzepacz P, Dillon J, Berger C, Carter D, et al. Fluoxetine improves functional work capacity in women with premenstrual dysphoric disorder. Archives of Women's Mental Health 2003;6:71-7.
  • Steiner M, Judge R, Brown E, Dillon J. Fluoxetine improves social functioning in women with premenstrual dysphoric disorder (PMDD). International Journal of Neuropsychopharmacology. 2000; Vol. 3, issue suppl1:247.
  • Steiner M, Judge R, Brown E, Dillon J. Fluoxetine's effect on food craving during the luteal phase in women with premenstrual dysphoric disorder (PMDD). International Journal of Gynecology and Obstetrics 2000;70(4):D147.
  • Steiner M, Romano S, Babcock S. Fluoxetine's efficacy in improving physical symptoms associated with PMDD. Journal of the European College of Neuropsychopharmacology 1999;9 Suppl 5:208.
  • Steiner M, Romano S, Babcock S. Fluoxetine's efficacy in improving physical symptoms associated with PMDD. Journal of the European College of Neuropsychopharmacology 2001;Suppl:208.
  • Steiner M, Romano S, Babcock, Dillon J, Shuler C, Berger C, et al. The efficacy of fluoxetine in improving physical symptoms associated with premenstrual dysphoric disorder. British Journal of Obstetrics and Gynaecology 2001;108:462-8.
  • Steiner M, Romano SJ, Babcock S, McCray S, Dillon JA. Efficacy of fluoxetine in improving mood symptoms, physical symptoms and social impairment in patients with PMDD. Journal of the European College of Neuropsychopharmacology 2001;Suppl:208.
  • Steiner M, Steinberg S, Stewart D, Carter D, Berger C, Reid R, et al. Fluoxetine in the treatment of premenstrual dysphoric disorder. The New England Journal of Medicine 1995;332:1529-34.
  • Steiner M, Trezepacz PT, Brown E. Premenstrual dysphoric disorder (PMDD) and work efficiency: Response to fluoxetine in a randomized clinical trial. European Neuropsychopharmacology 2000;10(3):226-7.
  • Steiner M, Trzepacz PT, Brown E. Premenstrual dysphoric disorder (PMDD) and work efficiency: response to fluoxetine in a randomized clinical trial. Journal of European College of Neuropsychopharmacology 2001;Suppl:226.
  • Trzepacz PT, Steiner M, Brown E. Premenstrual dysphoric disorder and work efficiency: Response to fluoxetine in a randomized clinical trial. Psychosomatics 2001;42(2):184.
  • Trzepacz PT, Steiner M, Brown E, Dillon J. Premenstrual dysphoric disorder and work efficiency: Response to fluoxetine in a randomized clinical trial. World Journal of Biological Psychiatry 2001;2 Suppl:340S.
Steiner 2005 {published data only}
  • Gee M, Bellew K, Holland F, Van Erp E, Perera P, McCafferty J. Luteal phase dosing of paroxetine controlled release is effective in treating PMDD. 156th Annual Meeting American Psychiatric Association, May 17-22 San Francisco, CA. 2003:NR760.
  • GlaxoSmithKline. A Double-Blind, Placebo-Controlled, 3-Arm, Fixed-Dose Study of Paroxetine CR Intermittent Dosing (12.5 mg and 25 mg) for Premenstrual Dysphoric Disorder [Study No 29060/717]. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F717&studyId=CA9A3538-05F2-43D8-A1E2-342281DDD178&compound=paroxetine Accessed 16 August 2012.
  • Steiner M, Hirschberg AL, Bergeron R, Holland F, Gee MD, Van Erp E. Luteal phase dosing with paroxetine controlled release (CR) in the treatment of premenstrual dysphoric disorder. American Journal of Obstetrics and Gynecology 2005;193:352-60.
Steiner 2008 {published data only}
  • GlaxoSmithKline. A randomized, double-blind, placebo-controlled trial of intermittent treatment with paroxetine 10mg/day and 20mg/day versus placebo in Canadian women with Premenstrual Dysphoric Disorder. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F621&studyId=8696C1BE-93D7-4883-AD54-2BC6CF7740BB&compound=paroxetine Accessed 16 August 2012.
  • Hamilton Health Sciences Corporation. Luteal Phase Administration of Paroxetine for the Treatment of PMDD: A Randomized, Double-Blind, Placebo-Controlled Trial in Canadian Women NCT00620581. http://clinicaltrials.gov/ct2/show/NCT00620581 2008.
  • Steiner M, Ravindran AV, LeMedello J-M, Carter D, Huang JO, Anonychuk AM, Simpson SD. Luteal phase administration of paroxetine for the treatment of premenstrual dysphoric disorder: a randomized, double-blind, placebo-controlled trial in Canadian women. Journal of Clinical Psychiatry 2008;69:991-8.
Stone 1991 {published data only}
Su 1997 {published data only}
Wikander 1998 {published data only}
  • Wikander I, Sunblad C, Andersch B, Dagnell I, Zylberstein D, Bengtsson F, et al. Citalopram in premenstrual dysphoria: Is intermittent treatment during luteal phases more effective than continuous medication throughout the menstrual cycle?. Journal of Clinical Psychopharmacology 1998;18:390-8.
Wood 1992 {published data only}
  • Wood SH, Mortola JF, Chan YF, Moossazadeh F, Yen SS. Treatment of premenstrual syndrome with fluoxetine: a double-blind, placebo-controlled, crossover study. Obstetrics and Gynecology 1992;80:339-44.
Yonkers 1997 {published data only}
  • Yonkers KA, Halbriech U, Freeman E, Brown C, Endicott J, Frank E, et al. Symptomatic improvement of premenstrual dysphoric disorder with sertraline treatment. JAMA 1997;278(12):983-8.
Young 1998 {published data only}
  • Young SA, Hurt PH, Benedeck DM, Howard RS. Treatment of PDD with sertraline during the luteal phase: a randomised, double-blind, placebo controlled crossover trial. Journal of Clinical Psychiatry 1998;59:76-80.
  • Young SA, Hurt PH, Benedek DM, Howard RS. Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: A randomized, double blind placebo controlled crossover trial. American Psychiatric Association 150th Annual Meeting, San Diego USA. 1997.
  • Young SA, Hurt PH, Benedek DM, Howard RS. Treatment of premenstrual dysphoric disorder with sertraline during the luteal phase: A randomized, double blind placebo controlled crossover trial. Journal of Clinical Psychiatry 1998;59:76-80.

References to studies excluded from this review

  1. Top of page
  2. Abstract摘要Résumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Alpay 2001 {published data only}
  • Alpay F, Turhan N. Intermittant versus continuous sertraline therapy in the treatment of premenstrual dysphoric disorders. International Journal of Fertility 2001;46:228-31.
Brandenburg 1993 {published data only}
De la Gandara 1997 {published data only}
  • De La Gandara Martin JJ. Trastorno disforico premenstrual: Tratamiento a largo plazo con fluoxetina y discontinuacion [Premenstrual dysphoric disorder:long term treatment with fluoxetine and discontinuation]. Actas Luso-Espanolas de Neurologia, Psiquiatria y Ciencias Afines 1997;25:235-42.
Diegoli 1998 {published data only}
  • Diegoli M, DaFonseca A, Diegoli CA, Pinotti JA. A double blind trial of four medications to treat severe premenstrual syndrome. International Journal of Gynecology and Obstetrics 1998;62:63-7.
Elks 1993 {published data only}
Flores Ramos 2003 {published data only}
  • Fores Ramos M, Ontiveros Uribe M, Cortes Sotres J. Comparison between continuous and intermittent treatment with citalopram..... [Comparacion entre el tratamiento continuo y el intermitente con citalopram para el trastorno disforico premenstrual]. Salud Mental 2003;26(003):37-45.
Freeman 1996 {published data only}
  • Freeman EW, Rickels K, Sondheimer SJ. Comparison of serotonergic and noradrenergic antidepressant medications in treatment of premenstrual syndrome (PMS). XXIst Collegium Internationale Neuro-psychopharmacologicum, Glasgow, Scotland. 12-16th July 1998.
  • Freeman EW, Rickels K, Sondheimer SJ. Sertraline versus desipramine in PMS treatment. 151st Annual Meeting of the American Psychiatric Association, Toronto, Canada. 30th May-4th June 1998, issue 118C.
  • Freeman EW, Rickels K, Sondheimer SJ, Wittmaack FM. Sertraline versus desipramine in the treatment of premenstrual syndrome: an open label trial. Journal of Clinical Psychiatry 1996;57:7-11.
Freeman 1999b {published data only}
  • Freeman EW, Rickels K, Arredono F, Lee-Chuan K, Pollack S, Sondheimer S. Full or half cycle treatment of severe premenstrual syndrome with a serotonergic antidepressant. Journal of Cliniical Psychopharmacology 1999;19(1):3-9.
Freeman 2000 {published data only}
  • Freeman EW, Sondheimer SJ, Polansky M, Garcia-Espagna B. Predictors of response to sertraline treatment of severe premenstrual syndromes. Journal of Clinical Psychiatry 2000;61(8):579-84.
Freeman 2002 {published data only}
  • Freeman E, Jabara S, Sondheimer S, Auletto R. Citalopram in PMS patients with prior SSRI treatment failure: A preliminary study. Journal of Womens Health & Gender-based Medicine 2002;11(5):459-64.
Freeman 2005 {published data only}
  • Freeman E, Sondheimer S, Sammel M, Ferdousi T, Lin H. A preliminary study of luteal phase versus symptom-onset dosing with escitalopram for premenstrual dysphoric disorder. Journal of Clinical Psychiatry 2005;66(6):769-73.
Glaxo 2002 {unpublished data only}
  • GlaxoSmithKline. A 3-Month, Double-blind, Placebo-controlled, Fixed-dose, Extension Study of Paroxetine CR (12.5 mg and 25 mg/day) Continuous Treatment for PMDD Patients Completing Studies 29060/677, 688 or 689 [Study no 29060/711]. http://www.gsk-clinicalstudyregister.com/result_detail.jsp?protocolId=29060%2F711&studyId=4A384A1A-46F7-4E8B-915B-4B324BB64491&compound=paroxetine Accessed 16 August 2012.
Landen 2009 {published data only}
  • Landen M, Erlandsson H, Bengtsson F, Andersch B, Eriksson E. Short onset of action of a serotonin reuptake inhibitor when used to reduce premenstrual irritability. Neuropsychopharmacology 2009;34:585-92.
Miller 2008 {published data only}
  • Miller MN, Newell CL, Miller BE, Frizzell PG, Kayser RA, Ferslew KE. Variable dosing of sertraline for premenstrual exacerbation of depression: a pilot study. Journal of Women's Health 2008;17(6):993-7.
Pearlstein 1994 {published data only}
Pearlstein 2000 {published data only}
  • Pearlstein T, Haskett R, Stout A, Frank E, Endicott J. Sertraline improves psychosocial functioning in premenstrual dysphoric disorder. 151st Annual Meeting of the American Psychiatric Association, 30th May- 4th June Toronto, Canada. 1998.
  • Pearlstein TB, Halbreich U, Batzar ED, Brown CS, Endicott J, Frank E, et al. Psychosocial functioning in women with premenstrual dysphoric disorder before and after treatment with sertraline or placebo. Journal of Clinical Psychiatry 2000;61(2):101-9.
Rickels 1990 {published data only}
Steiner 1997 {published data only}
  • Steiner M, Korzekwa MI, Lamont J, Wilkins A. Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria. Psychopharmacology Bulletin 1997;33:771-4.
Sundblad 1992 {published data only}
Sundblad 1993 {published data only}
  • Sundblad C, Hedberg M, Eriksson E. Clomipramine administered during the luteal phase reduces the symptoms of premenstrual syndrome: A placebo controlled trial. Neuropsychopharmacology 1993;9(2):133-45.
Sundblad 1997 {published data only}
  • Sundblad C Wikander I, Andersch B, Eriksson E. A naturalistic study of paroxetine in premenstrual syndrome: efficacy and side-effects during ten cycles of treatment. European Neuropsychopharmacology 1997;7(3):201-6.
Veeninga 1990 {published data only}
Wu 2008 {published data only}
Yonkers 1996 {published data only}
Yonkers 2002 {unpublished data only}
  • Yonkers KA. Antidepressant Treatment for Premenstrual Syndrome and Premenstrual Dysphoric Disorder. http://clinicaltrials.gov/ct2/show/NCT00048854.
Yonkers 2006 {published data only}

References to ongoing studies

  1. Top of page
  2. Abstract摘要Résumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
Yonkers 2007 {unpublished data only}
  • Yonkers KA, Altemus M, Kornstein S. Evaluating the Effectiveness of Sertraline in Treating Women With Premenstrual Dysphoric Disorder. http://www.clinicaltrials.gov/ct2/show/NCT00536198 2007.
Yonkers 2010 {unpublished data only}
  • Yonkers KA. Comparison of Fluoxetine, Calcium and Placebo for the Treatment of Moderate to Severe Premenstrual Syndrome (PMS). http://clinicaltrials.gov/ct2/show/NCT00965562 2010.

Additional references

  1. Top of page
  2. Abstract摘要Résumé
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. History
  15. Contributions of authors
  16. Declarations of interest
  17. Sources of support
  18. Differences between protocol and review
  19. Characteristics of studies
  20. References to studies included in this review
  21. References to studies excluded from this review
  22. References to ongoing studies
  23. Additional references
  24. References to other published versions of this review
ACOG 2000
  • American College of Obstetricians and Gynecologists. Premenstrual syndrome. ACOG PracticeBulletin No. 15. Washington, DC: ACOG 2000.
APA 2000
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC:American Psychiatric Association; 2000. p. 774. Diagnostic and statistical manual of mental disorders. 4th Edition. Washington, DC: American Psychiatric Association, 2000:774.
Baker 2012
Cohen 1988a
  • Cohen J. Statistical Power Analysis in the Behavioral Sciences (2nd edition). Statistical Power Analysis in the Behavioral Sciences. 2nd Edition. Hillsdale (NJ): Lawrence Erlbaum Associates, Inc., 1988.
Epperson 2012
  • Epperson CN, Steiner M, Hartlage SA, Erikkson E, Schmidt PJ, Jones I, Yonkers KA. Premenstrual Dysphoric Disorder: Evidence for a New Category for DSM-5. American Journal of Psychiatry 2012;169(5):465-75.
Ford 2012
Freeman 2009
  • Freeman EW, Rickels K, Sammel MD, Lin H, Sondheimer SS. Time to relapse after short-term or long-term sertraline treatment for severe premenstrual syndromes. Archives of General Psychiatry 2009;66(5):537-44.
Freeman 2012
  • Freeman EW, Sammel MD, Lin H, Rickels K, Sondheimer SJ. Clinical subtypes of premenstrual syndrome and responses to sertraline treatment. Obstetrics and Gynecology 2011;118(6):1293-1300.
Glaxo 2012
  • GlaxoSmithKline Government Affairs, Public Policy, Patient Advocacy. Public Disclosure of Clinical Research. Downloaded from: http://www.google.co.nz/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CDAQFjAA&url=http%3A%2F%2Fwww.gsk.com%2Fpolicies%2FGSK-on-disclosure-of-clinical-trial-information.pdf&ei=lqIIUee4GuTDmQX9hoD4Ag&usg=AFQjCNEcA2G3XGrrh9BkqK1RedmQ53VgQg&bvm=bv.41642243,d.dGY.
Halbreich 2008
  • Halbreich U. Selective serotonin reuptake inhibitors and initial oral contraceptives for the treatment of PMDD: effective but not enough. CNS Spectrum 2008;13(7):566,569-72.
Higgins 2011
  • Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011 ]. Available from www.cochrane-handbook.org.
Ismail 2006
  • Ismail KMK, Crome IB, O'Brien PMS. In: Higham J editor(s). Psychological disorders in obstetrics and gynaecology for the MRCOG and beyond. London: The Royal College of Obstetricicians and Gynaecologists, 2006:37.
Jing 2009
Kleinstauber 2012
  • Kleinstauber M, Witthoft M, Hiller W. Cognitive-behavioral and pharmacological interventions for premenstrual syndrome or premenstrual dysphoric disorder: a meta-analysis. Journal of Clinical Psychology in Medical Settings 2012;19:308-19.
Lopez 2012
Magos 1986
  • Magos AL, Brincat M, Studd JW. Trend analysis of the symptoms of 150 women with a history of th premenstrual syndrome. American Journal of Obstetrics and Gynecology 1986;155(2):277-82.
Micromedex 2013
  • DRUGDEX® Evaluations. Micromedex.2 database Accessed 2.5.13 via University of Auckland library.
Naheed 2013
  • Naheed B, O'Brien PMS, Uthman OA, O'Mahony F. Non-contraceptive oestrogen-containing preparations for controlling symptoms of premenstrual syndrome. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD010503]
O'Brien 2011
  • O'Brien PMS, Backstrom T, Brown C, Dennerstein L, Endicott J, Epperson CN, et al. Towards a consensus on diagnostic criteria, measurement and trial design of the premenstrual disorders: the ISPMD Montreal consensus. Archives of Womens Mental Health 2011;14:13-21.
Pearlstein 2002
Pearlstein 2007
  • Pearlstein T. Prevalence, impact, on morbidity and burden of disease. In: O’Brien PMS, Rapkin A, Schmidt P editor(s). The premenstrual syndromes: PMS and PMDD. London: Informa Healthcare, 2007:37-47.
Plouffe 1993
  • Plouffe L, Stewart K, Craft KS, Maddox MS, Rausch MD. Diagnostic and treatment results from a south-eastern academic center-based premenstrual syndrome clinic: The first year. Americal Journal of Obstetrics and Gynecology 1993;169(2):295-307.
Rapkin 2008
Shah 2008
  • Shah NJ, Jones JB, Aperi J, Shemtov R, Karne A. Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. A meta-analysis. Obstetrics and Gynecology 2008;111(5):1175-82.
Shaw 2003
  • Shaw S, Wyatt K, Campbell J, Ernst E, Thompson-Coon J. Vitex agnus castus for premenstrual syndrome. Cochrane Database of Systematic Reviews 2003, Issue 4. [DOI: 10.1002/14651858.CD004632]
Yu 2005
  • Yu J, Liu B, Liu Z, Welch V, Wu T, Clarke J, Smith CA. Acupuncture for premenstrual syndrome. Cochrane Database of Systematic Reviews 2005, Issue 2. [DOI: 10.1002/14651858.CD005290]