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.
CONCLUSIONS: 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: clinicaltrials.gov Identifier: NCT00620581.