Selective serotonin reuptake inhibitors for premenstrual syndrome

Obstetrics and Gynaecology, University of Auckland, FMHS, Auckland, New Zealand.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 01/2009; 6(2):CD001396. DOI: 10.1002/14651858.CD001396.pub2
Source: PubMed


This is a substantive update of a previous review. Severe premenstrual syndrome (PMS) affects between 3% to 5% of women of reproductive age. Severe PMS is classified under the Diagnostic and Statistical Manual of Mental Disorders as premenstrual dysphoric disorder (PMDD). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as front-line therapy for PMS. A systematic review was undertaken on the efficacy of SSRIs in the management of severe PMS, or PMDD, to assess the evidence for this treatment option.
The objective of this review was to evaluate the effectiveness of SSRIs in reducing premenstrual syndrome symptoms in women diagnosed with severe premenstrual syndrome.
Electronic searches for relevant randomised controlled trials 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 (March 2008). Where insufficient data were presented in a report the original authors were contacted for further details.
All trials 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 in a blinded trial.
Forty randomised controlled trials were identified which reported the use of SSRIs in the management of PMS. Fifty-six trials were excluded. The review authors extracted the data independently and estimated standardised mean differences for continuous outcomes.
Due to heterogeneity, analyses were subgrouped into change and absolute scores. The primary analysis of reduction in overall symptomatology included data on 2294 women with premenstrual syndrome. SSRIs were found to be highly effective in treating the premenstrual symptoms (SMD -0.53, 95% CI 0.68 to -0.39; P < 0.00001). Secondary analysis showed that they were effective in treating physical (SMD -0.34, 95% CI -0.45 to -0.22; P < 0.00001), functional (SMD -0.30, 95% CI -0.43 to -0.17; P < 0.00001), and behavioural symptoms (SMD -0.41, 95% CI -0.53 to -0.29; P < 0.00001). Luteal phase only and continuous administration were both effective and there was no influence of a placebo run-in period on reduction in symptoms. All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms. Withdrawals due to side effects were twice as likely to occur in the treatment group (OR 2.18, 95% CI 1.62 to 2.92; P < 0.00001).
The evidence supports the use of selective serotonin reuptake inhibitors in the management of severe premenstrual syndrome.

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Available from: Julie Anne Brown, Oct 04, 2015
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    • "Already widely prescribed as antidepressants, selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, have gained increasing acceptance since the 1990s (Steiner et al., 1995) as treatments for premenstrual dysphoric disorder (PMDD) and the more common but loosely defined premenstrual syndrome (see Marjoribanks et al., 2013). The former is a debilitating condition (Dennerstein et al., 2010) that includes both mood and physical symptoms such as irritability, anxiety, outbursts of anger, fatigue, sleep disturbance and hyperalgesia, and is thought at least in part to be triggered by the withdrawal of endogenous progesterone (see Backstrom et al., 2003). "
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    ABSTRACT: Background and purpose: Fluoxetine, a selective serotonin reuptake inhibitor, elevates brain concentrations of the neuroactive progesterone metabolite allopregnanolone, an effect suggested to underlie its use in the treatment of premenstrual dysphoria. One report showed fluoxetine to activate the aldo-keto reductase (AKR) component of 3α-hydroxysteroid dehydrogenase (3α-HSD), which catalyses production of allopregnanolone from 5α-dihydroprogesterone. However, this action was not observed by others. The present study sought to clarify the site of action for fluoxetine in elevating brain allopregnanolone. Experimental approach: Adult male rats and female rats in dioestrus were treated with fluoxetine and their brains assayed for allopregnanolone and its precursors, progesterone and 5α-dihydroprogesterone. Subcellular fractions of rat brain were also used to investigate the actions of fluoxetine on 3α-HSD activity in both the reductive direction, producing allopregnanolone from 5α-dihydroprogesterone, and the reverse oxidative direction. Fluoxetine was also tested on these recombinant enzyme activities expressed in HEK cells. Key results: Short-term treatment with fluoxetine increased brain allopregnanolone concentrations in female, but not male, rats. Enzyme assays on native rat brain fractions and on activities expressed in HEK cells showed fluoxetine did not affect the AKR producing allopregnanolone from 5α-dihydroprogesterone but did inhibit the microsomal dehydrogenase oxidizing allopregnanolone to 5α-dihydroprogesterone. Conclusions and implications: Fluoxetine elevated allopregnanolone in female rat brain by inhibiting its oxidation to 5α-dihydroprogesterone by a microsomal dehydrogenase. This is a novel site of action for fluoxetine, with implications for the development of new agents and/or dosing regimens to raise brain allopregnanolone.
    British Journal of Pharmacology 08/2014; 171(24). DOI:10.1111/bph.12891 · 4.84 Impact Factor
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    • "These pharmacologic approaches are associated with side effects that obviously concern women with PMS. As a result, compliance in women with PMS treated with SSRIs is rather poor due to adverse drug effects, such as headache, weight gain, drowsiness, sexual dysfunction, and insomnia [13,14]. As well, prescriptions of alprazolam are limited due to drug dependence, intolerance or even abuse [8]. "
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    ABSTRACT: Background Premenstrual syndrome (PMS) occurs in women during their reproductive age with a quite negative impact on their daily lives. Women with PMS experience a wide range of physical or psychological symptoms and seek treatment for them. Chinese herb medicine (CHM) is commonly used for PMS and the goal of this study is to investigate the prescription patterns of CHM for PMS by using a nationwide database. Methods Prescriptions of CHM were obtained from two million beneficiaries randomly sampled from the National Health Insurance Research Database, a nationwide database in Taiwan. The ICD-9 code 625.4 was used to identify patients with PMS. Association rule mining and social network analysis were used to explore both the combinations and the core treatments for PMS. Results During 1998-2011, a total of 14,312 CHM prescriptions for PMS were provided. Jia-Wei-Xiao-Yao-San (JWXYS) was the CHM which had the highest prevalence (37.5% of all prescriptions) and also the core of prescription network for PMS. For combination of two CHM, JWXYS with Cyperus rotundus L. was prescribed most frequently, 7.7% of all prescriptions, followed by JWXYS with Leonurus heterophyllus Sweet, 5.9%, and Cyperus rotundus L. with Leonurus heterophyllus Sweet, 5.6%. Conclusions JWXYS-centered CHM combinations were most commonly prescribed for PMS. To the best of our knowledge, this is the first pharmaco-epidemiological study to review CHM treatments for PMS. However, the efficacy and safety of these commonly used CHM were still lacking. The results of this study provide valuable references for further clinical trials and bench studies.
    BMC Complementary and Alternative Medicine 06/2014; 14(1):206. DOI:10.1186/1472-6882-14-206 · 2.02 Impact Factor
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    • "The most widely accepted current theory holds that gonadal steroid hormones and cyclic changes in the level of central neurotransmitters affect mood and behavior during the luteal phase and trigger the disease in women who are predisposed to PMS [3]. Despite the evidence demonstrating the role of β-endorphin and gamma-aminobutyric acid in the etiology of PMS, serotonin is the most accused neurotransmitter [23,24]. However, a clear relationship between serotonin and PMS has not yet been proven [6]. "
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    ABSTRACT: Objective The objective of this study was to investigate whether there was a correlation between catechol-o-methyltransferase (COMT) gene polymorphism, which is believed to play a role in the etiology of psychotic disorders, and premenstrual syndrome (PMS). Methods Fifty-three women with regular menstrual cycles, aged between 18 and 46 years and diagnosed with PMS according to the American Congress of Obstetrics and Gynecology criteria were included in this study as the study group, and 53 healthy women having no health problems were selected as the controls. Venous blood was collected from all patients included in the study and kept at -18℃ prior to analysis. Results There was no significant difference between the groups in terms of demographic features such as age, body mass index, number of pregnancies, parity, and number of children. No statistically significant difference was observed in terms of COMT gene polymorphism (p=0.61) between women in the PMS and the control groups. However, a significant difference was found between arthralgia, which is an indicator of PMS, and low-enzyme activity COMT gene (Met/Met) polymorphism (p=0.04). Conclusion These results suggested that there was no significant relationship between PMS and COMT gene polymorphism. Since we could not find a direct correlation between the COMT gene polymorphism and PMS, further studies including alternative neurotransmitter pathways are needed to find an effective treatment for this disease.
    Clinical and Experimental Reproductive Medicine 06/2014; 41(2):62-7. DOI:10.5653/cerm.2014.41.2.62
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