Selective serotonin reuptake inhibitors for premenstrual syndrome
TL;DR: SSRIs were found to be highly effective in treating premenstrual symptoms and there was no significant difference between trials funded by pharmaceutical companies and those independently funded.
Abstract: Background
Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.
Objectives
The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.
Search methods
Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.
Selection criteria
Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome.
Data collection and analysis
Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.
Main results
Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I2 = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I2=29%), moderate quality evidence).
SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.
Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I2 = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.
The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.
Authors' conclusions
SSRIs are effective in reducing the symptoms of PMS, whether taken in the luteal phase only or continuously. Adverse effects are relatively frequent, the most common being nausea and asthenia. Adverse effects are dose-dependent.
Citations
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TL;DR: Recommendations for a stepped care approach that differentiates between uncomplicated and complicated FSS are given, and a balance between biomedical, organ-oriented, and cognitive interpersonal approaches is most appropriate at this truly psychosomatic interface.
626 citations
TL;DR: To the extent that behavioral changes have been demonstrated over the course of the menstrual cycle, the best evidence suggests that differences in sexually dimorphic tasks are small and difficult to replicate.
Abstract: The menstrual cycle has attracted research interest ever since the 1930s. For many researchers the menstrual cycle is an excellent model of ovarian steroid influence on emotion, behavior, and cognition. Over the past years methodological improvements in menstrual cycle studies have been noted, and this review summarizes the findings of methodologically sound menstrual cycle studies in healthy women. Whereas the predominant hypotheses of the cognitive field state that sexually dimorphic cognitive skills that favor men are improved during menstrual cycle phases with low estrogen and that cognitive skills that favor women are improved during cycle phases with increased estrogen and/or progesterone, this review has not found sufficient evidence to support any of these hypotheses. Mental rotation has gained specific interest in this aspect, but a meta-analysis yielded a standardized mean difference in error rate of 1.61 (95% CI -0.35 to 3.57), suggesting, at present, no favor of an early follicular phase improvement in mental rotation performance. Besides the sexually dimorphic cognitive skills, studies exploring menstrual cycle effects on tasks that probe prefrontal cortex function, for instance verbal or spatial working memory, have also been reviewed. While studies thus far are few, results at hand suggest improved performance at times of high estradiol levels. Menstrual cycle studies on emotional processing, on the other hand, tap into the emotional disorders of the luteal phase, and may be of relevance for women with premenstrual disorders. Although evidence at present is limited, it is suggested that emotion recognition, consolidation of emotional memories, and fear extinction is modulated by the menstrual cycle in women. With the use of functional magnetic resonance imaging, several studies report changes in brain reactivity across the menstrual cycle, most notably increased amygdala reactivity in the luteal phase. Thus, to the extent that behavioral changes have been demonstrated over the course of the menstrual cycle, the best evidence suggests that differences in sexually dimorphic tasks are small and difficult to replicate. However, emotion-related changes are more consistently found, and are better associated with progesterone than with estradiol such that high progesterone levels are associated with increased amygdala reactivity and increased emotional memory.
252 citations
Journal Article•
TL;DR: The Daily Record of Severity of Problems is one tool with which women may self-report the presence and severity of premenstrual symptoms that correlate with the criteria for pre menstrual dysphoric disorder in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.
Abstract: Premenstrual syndrome is defined as recurrent moderate psychological and physical symptoms that occur during the luteal phase of menses and resolve with menstruation. It affects 20 to 32 percent of premenopausal women. Women with premenstrual dysphoric disorder experience affective or somatic symptoms that cause severe dysfunction in social or occupational realms. The disorder affects 3 to 8 percent of premenopausal women. Proposed etiologies include increased sensitivity to normal cycling levels of estrogen and progesterone, increased aldosterone and plasma renin activity, and neurotransmitter abnormalities, particularly serotonin. The Daily Record of Severity of Problems is one tool with which women may self-report the presence and severity of premenstrual symptoms that correlate with the criteria for premenstrual dysphoric disorder in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision. Symptom relief is the goal for treatment of premenstrual syndrome and premenstrual dysphoric disorder. There is limited evidence to support the use of calcium, vitamin D, and vitamin B6 supplementation, and insufficient evidence to support cognitive behavior therapy. Serotonergic antidepressants (citalopram, escitalopram, fluoxetine, sertraline, venlafaxine) are first-line pharmacologic therapy.
247 citations
TL;DR: Drospirenone/EE, given in a 24/4 regimen, was superior to placebo for improving symptoms associated with PMDD.
229 citations
Cites background from "Selective serotonin reuptake inhibi..."
...The selective serotonin reuptake inhibitors (SSRIs) are generally considered the first-line treatment option and are the only FDA-approved treatments for PMDD [15,18,22–25]....
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TL;DR: The results suggest a bidirectional association between depression and obesity in middle-aged and elderly women and underscore the importance of early detection and proper behavioral modifications to lower the burden of both conditions.
Abstract: Although it has been hypothesized that the depression–obesity relation is bidirectional, few studies have addressed this hypothesis in a prospective setting. We aimed to examine the bidirectional relationship in middle-aged and elderly women. A total of 65 955 women aged 54–79 years in the Nurses’ Health Study were prospectively followed from 1996 to 2006 with updated information on body weight, depression status and various covariates every 2 years. Depression was defined as self-report of physician-diagnosed depression and/or antidepressant use. Obesity was defined as a BMI ⩾30.0 kg m−2. The first three waves (1996–2000) were used as the baseline period and the last three waves (2002–2006) were used as the follow-up period. After adjusting for baseline age, physical activity, comorbidities, BMI and other covariates, depression at the baseline period was associated with an increased risk of obesity at the follow-up period in all women (multivariate-adjusted odds ratio (OR), 1.38; 95% confidence interval (95% CI), 1.24–1.53) and baseline non-obese women (OR, 1.51; 95% CI, 1.36–1.67). In the opposite direction, after adjusting for baseline age, physical activity, comorbidities, depression status and other covariates, obese women at baseline had a moderately increased risk of depression at the follow-up period compared with normal-weight women (OR, 1.11; 95% CI, 1.03–1.18), and this association was similar for new onset of depression (OR for obese versus normal weight women, 1.10; 95% CI, 1.02–1.20). Our results suggest a bidirectional association between depression and obesity in middle-aged and elderly women. Future studies are needed to confirm our findings in different populations, and investigate the potential mechanisms underlying this association. Our results underscore the importance of early detection and proper behavioral modifications to lower the burden of both conditions.
228 citations
References
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11 Jun 2013
113,134 citations
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
TL;DR: An instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research is described and its use to determine the effect of rater blinding on the assessments of quality is described.
15,740 citations
TL;DR: A systematic review and meta-analysis of placebo-controlled studies examined the efficacy and tolerability of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products in adults with somatoform disorders in adults to improve optimal treatment decisions.
Abstract: BACKGROUND: Somatoform disorders are characterised by chronic, medically unexplained physical symptoms (MUPS). Although different medications are part of treatment routines for people with somatoform disorders in clinics and private practices, there exists no systematic review or meta-analysis on the efficacy and tolerability of these medications. We aimed to synthesise to improve optimal treatment decisions.OBJECTIVES: To assess the effects of pharmacological interventions for somatoform disorders (specifically somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, and pain disorder) in adults.SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 17 January 2014). This register includes relevant randomised controlled trials (RCTs) from The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). To identify ongoing trials, we searched ClinicalTrials.gov, Current Controlled Trials metaRegister, the World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry. For grey literature, we searched ProQuest Dissertation {\&} Theses Database, OpenGrey, and BIOSIS Previews. We handsearched conference proceedings and reference lists of potentially relevant papers and systematic reviews and contacted experts in the field.SELECTION CRITERIA: We selected RCTs or cluster RCTs of pharmacological interventions versus placebo, treatment as usual, another medication, or a combination of different medications for somatoform disorders in adults. We included people fulfilling standardised diagnostic criteria for somatisation disorder, undifferentiated somatoform disorder, somatoform autonomic dysfunction, or somatoform pain disorder.DATA COLLECTION AND ANALYSIS: One review author and one research assistant independently extracted data and assessed risk of bias. Primary outcomes included the severity of MUPS on a continuous measure, and acceptability of treatment.MAIN RESULTS: We included 26 RCTs (33 reports), with 2159 participants, in the review. They examined the efficacy of different types of antidepressants, the combination of an antidepressant and an antipsychotic, antipsychotics alone, or natural products (NPs). The duration of the studies ranged between two and 12 weeks.One meta-analysis of placebo-controlled studies showed no clear evidence of a significant difference between tricyclic antidepressants (TCAs) and placebo for the outcome severity of MUPS (SMD -0.13; 95{\%} CI -0.39 to 0.13; 2 studies, 239 participants; I(2) = 2{\%}; low-quality evidence). For new-generation antidepressants (NGAs), there was very low-quality evidence showing they were effective in reducing the severity of MUPS (SMD -0.91; 95{\%} CI -1.36 to -0.46; 3 studies, 243 participants; I(2) = 63{\%}). For NPs there was low-quality evidence that they were effective in reducing the severity of MUPS (SMD -0.74; 95{\%} CI -0.97 to -0.51; 2 studies, 322 participants; I(2) = 0{\%}).One meta-analysis showed no clear evidence of a difference between TCAs and NGAs for severity of MUPS (SMD -0.16; 95{\%} CI -0.55 to 0.23; 3 studies, 177 participants; I(2) = 42{\%}; low-quality evidence). There was also no difference between NGAs and other NGAs for severity of MUPS (SMD -0.16; 95{\%} CI -0.45 to 0.14; 4 studies, 182 participants; I(2) = 0{\%}).Finally, one meta-analysis comparing selective serotonin reuptake inhibitors (SSRIs) with a combination of SSRIs and antipsychotics showed low-quality evidence in favour of combined treatment for severity of MUPS (SMD 0.77; 95{\%} CI 0.32 to 1.22; 2 studies, 107 participants; I(2) = 23{\%}).Differences regarding the acceptability of the treatment (rate of all-cause drop-outs) were neither found between NGAs and placebo (RR 1.01, 95{\%} CI 0.64 to 1.61; 2 studies, 163 participants; I(2) = 0{\%}; low-quality evidence) or NPs and placebo (RR 0.85, 95{\%} CI 0.40 to 1.78; 3 studies, 506 participants; I(2) = 0{\%}; low-quality evidence); nor between TCAs and other medication (RR 1.48, 95{\%} CI 0.59 to 3.72; 8 studies, 556 participants; I(2) =14{\%}; low-quality evidence); nor between antidepressants and the combination of an antidepressant and an antipsychotic (RR 0.80, 95{\%} CI 0.25 to 2.52; 2 studies, 118 participants; I(2) = 0{\%}; low-quality evidence). Percental attrition rates due to adverse effects were high in all antidepressant treatments (0{\%} to 32{\%}), but low for NPs (0{\%} to 1.7{\%}).The risk of bias was high in many domains across studies. Seventeen trials (65.4{\%}) gave no information about random sequence generation and only two (7.7{\%}) provided information about allocation concealment. Eighteen studies (69.2{\%}) revealed a high or unclear risk in blinding participants and study personnel; 23 studies had high risk of bias relating to blinding assessors. For the comparison NGA versus placebo, there was relatively high imprecision and heterogeneity due to one outlier study. Although we identified 26 studies, each comparison only contained a few studies and small numbers of participants so the results were imprecise.AUTHORS' CONCLUSIONS: The current review found very low-quality evidence for NGAs and low-quality evidence for NPs being effective in treating somatoform symptoms in adults when compared with placebo. There was some evidence that different classes of antidepressants did not differ in efficacy; however, this was limited and of low to very low quality. These results had serious shortcomings such as the high risk of bias, strong heterogeneity in the data, and small sample sizes. Furthermore, the significant effects of antidepressant treatment have to be balanced against the relatively high rates of adverse effects. Adverse effects produced by medication can have amplifying effects on symptom perceptions, particularly in people focusing on somatic symptoms without medical causes. We can only draw conclusions about short-term efficacy of the pharmacological interventions because no trial included follow-up assessments. For each of the comparisons where there were available data on acceptability rates (NGAs versus placebo, NPs versus placebo, TCAs versus other medication, and antidepressants versus a combination of an antidepressant and an antipsychotic), no clear differences between the intervention and comparator were found.Future high-quality research should be carried out to determine the effectiveness of medications other than antidepressants, to compare antidepressants more thoroughly, and to follow-up participants over longer periods (the longest follow up was just 12 weeks). Another idea for future research would be to include other outcomes such as functional impairment or dysfunctional behaviours and cognitions as well as the classical outcomes such as symptom severity, depression, or anxiety.
11,458 citations
Book•
01 Jan 1964
TL;DR: A premenstrual exacerbation of an underlying disease is therefore not, by definition, preMenstrual syndrome (PMS), but is sometimes referred to as menstrual distress, as the patient will have symptoms throughout the menstrual cycle.
Abstract: A premenstrual exacerbation of an underlying disease is therefore not, by definition, premenstrual syndrome (PMS) but is sometimes referred to as menstrual distress, as the patient will have symptoms throughout the menstrual cycle.
1,791 citations