The efficacy of fluoxetine in improving physical symptoms associated with premenstrual dysphoric disorder

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Abstract

Objective To determine the effectiveness of fluoxetine in alleviating physical symptoms of premenstrual dysphoric disorder.

Design Randomised, double-blind, placebo controlled, parallel study.

Setting Canadian University based outpatient clinics.

Participants Four hundred and five subjects, of whom 320 with prospectively determined premenstrual dysphoric disorder were randomised.

Methods Randomised women were assigned to fluoxetine 20 or 60 mg/day or placebo. Common physical symptoms associated with premenstrual dysphoric disorder including breast tenderness, bloating, and headache were evaluated by visual analog scales and the self-rated and observer premenstrual tension syndrome scales.

Outcome measures Luteal phase change from mean baseline scores to mean treatment scores for all scales.

Results Fluoxetine treatment was statistically superior to placebo, with no significant differences between the two fluoxetine dosages in their effects on physical symptoms.

Conclusion Daily fluoxetine treatment is superior to placebo in improving the most common physical symptoms associated with premenstrual dysphoric disorder.

Introduction

Premenstrual dysphoric disorder, as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition1, is a severe variant of premenstrual syndrome (PMS). Premenstrual dysphoric disorder affects from 3% to 8% of women in their reproductive years2., 3., 4.. Premenstrual dysphoric disorder is characterised by a significant mood disturbance that appears during the week prior to onset of menses (the late luteal phase) and remits following the start of menstrual flow. The diagnosis of premenstrual dysphoric disorder requires persistence of this luteal mood disturbance, which includes tension, irritability, affective lability, and depression. Physical symptoms, such as breast tenderness, bloating, headache, and joint and muscle pain, frequently accompany the prominent dysphoria of premenstrual dysphoric disorder and contribute to occupational and social impairment during the late luteal phase of the menstrual cycle.

Many treatments have been utilised in the management of premenstrual symptoms, including hormonal therapies and, in the most severe cases, surgical intervention. More recently, the serotonergic agents, including specific serotonic reuptake inhibitors, have been shown to be effective at improving the mood symptoms associated with premenstrual dysphoric disorder5., 6., 7., 8., 9., 10., 11., 12.. Less has been described regarding their efficacy at reducing accompanying physical complaints. The current study evaluates data from a multicenter trial of the specific serotonergic re-uptake inhibitor fluoxetine in the treatment of premenstrual dysphoric disorder, specifically addressing physical symptomatology.

Section snippets

Methods

This was a randomised, double-blind, placebo-controlled, parallel study of 405 women, of whom 320 were randomised, designed to evaluated the efficacy of fluoxetine 20 mg/day and 60 mg/day in the management of premenstrual dysphoric disorder. The women were randomised to six menstrual cycles of double-blind treatment following a two-cycle, single-blind, placebo run-in period (Fig. 1). A detailed description of the study has been published previously12.

Results

Three hundred and twenty women (mean age, 36 ±5 years) with prospectively confirmed premenstrual dysphoric disorder were randomised to one of three treatment sequence groups: fluoxetine 20 mg/day (n=104), or fluoxetine 60 mg/day (n=108), or placebo (n=108). The treatment groups were comparable at baseline with respect to demographics.

Discussion

Daily fluoxetine treatment improved physical symptoms in women with premenstrual dysphoric disorder when symptoms were measured using a VAS physical scale, the individual VAS items (except headache), and the PMTS-SR and PMTS-O physical symptoms subtotals. Fluoxetine 20 mg/day produced similar improvement compared with fluoxetine 60 mg/day. This is the largest trial to date documenting that, in addition to improving mood, fluoxetine improved physical discomfort associated with premenstrual

Conclusion

Daily fluoxetine treatment significantly improved physical symptoms in women with severe premenstrual dysphoria. Fluoxetine treatment at 20 mg/day was as efficacious as 60 mg/day and was more tolerable than the higher dose. Future studies are required to determine whether intermittent fluoxetine dosing is as efficacious as daily fluoxetine dosing in improving physical symptoms associated with the premenstruum.

Acknowledgements

This work was funded by Eli Lilly Co.

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