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Luteal Phase Administration of Paroxetine for the Treatment of Premenstrual Dysphoric Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial in Canadian Women

Meir Steiner, M.D., Ph.D., F.R.C.P.(C); Arun V. Ravindran, M.B., Ph.D., F.R.C.P.(C), F.R.C.Psych.; Jean-Michel LeMelledo, M.D.; Diana Carter, M.D., F.R.C.P.(C); Jenny O. Huang, M.Sc.; Andrea M. Anonychuk, M.Sc.; and Scott D. Simpson, Ph.D.

Objective: To evaluate the efficacy and safety of intermittent, luteal phase-only administration of paroxetine (10 mg and 20 mg) in the treatment of premenstrual dysphoric disorder (PMDD).

Method: In this multicenter trial, female outpatients (aged 18-45 years) from 4 Canadian health centers meeting DSM-IV criteria for PMDD were asked to perform daily ratings of their premenstrual symptoms for 2 consecutive menstrual cycles. Those displaying the symptoms of irritability and/or depressed mood in the luteal phases but not in the follicular phases of their menstrual cycles were randomly assigned to intermittent, luteal phase-only treatment with paroxetine 10 mg or 20 mg or placebo for 4 additional cycles. The primary efficacy endpoint was the percent change from baseline at study endpoint on the visual analog scale irritability score. Treatment differences were tested using analysis of covariance ad hoc. Estimated treatment mean differences and their associated 95% confidence intervals were also calculated. Data were collected from May 1999 to November 2002.

Results: Ninety-nine patients were included in the intention-to-treat population. When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects.

Conclusion: Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD. These results are consistent with previous studies suggesting that PMDD may be treated effectively by luteal phase-only administration of a selective serotonin reuptake inhibitor.

Trial Registration: Identifier: NCT00620581


(J Clin Psychiatry 2008;69:991-998. Online Ahead of Print May 27, 2008.)

Received June 26, 2007; accepted Sept. 18, 2007. From the Departments of Psychiatry and Behavioral Neurosciences and Obstetrics and Gynecology, McMaster University and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, Ontario (Dr. Steiner); the Department of Psychiatry, University of Toronto and Centre for Addiction and Mental Health, Toronto, Ontario (Dr. Ravindran); the Department of Psychiatry, University of Alberta, Edmonton (Dr. LeMelledo); British Columbia Women's Reproductive Psychiatric Program, Vancouver (Dr. Carter); Biomedical Data Sciences, GlaxoSmithKline Canada, Oakville, Ontario (Ms. Huang); and Statistics and Epidemiology (Ms. Anonychuk) and Medical Affairs (Dr. Simpson), GlaxoSmithKline Canada, Mississauga, Ontario, Canada.

This study was funded by GlaxoSmithKline, Canada.

The authors would like to thank Stephanie Duench, M.S. (University of Waterloo, Ontario, Canada) for her assistance with the preparation of this manuscript. Ms. Duench has no conflict of interest to report.

Financial disclosure appears at the end of the article.

Corresponding author and reprints: Meir Steiner, M.D., Ph.D., F.R.C.P.(C), St. Joseph's Healthcare, Hamilton, Ontario, Canada L8N 4A6 (e-mail: