BACKGROUND: Better characterization of safety and efficacy of multiple doses of 
selective serotonin reuptake inhibitors for the treatment of a wider range of 
symptoms of premenstrual dysphoric disorder (PMDD) will provide clinicians with 
flexibility to provide symptom relief along with acceptable tolerability. This 
study was designed to assess the efficacy and tolerability of multiple doses of 
paroxetine controlled release (CR) in PMDD.
METHODS: In a multicenter (43 outpatient U.S. sites), placebo-controlled trial, 
327 females aged 18 to 45 years, with regular menstrual cycles, meeting DSM-IV 
criteria for PMDD, were randomly assigned to receive paroxetine CR 12.5 mg; 
paroxetine CR 25 mg; or placebo, once daily, for up to three treatment cycles. 
The primary efficacy outcome was change from baseline to end point in mean 
luteal phase Visual Analogue Scale-Mood (irritability, tension, affective 
lability, depressed mood) score.
RESULTS: At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) 
demonstrated significant improvement in VAS-Mood scores compared with those who 
received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, 
-8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment 
difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001). Results were 
also significant across measures of physical symptoms and social functioning. 
Paroxetine CR was well tolerated; 9.5% of subjects treated with 12.5 mg and 
13.5% of subjects treated with 25 mg withdrew from the trial due to adverse 
events, compared with 6.5% of subjects in the placebo group.
CONCLUSIONS: Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective 
and well tolerated in patients who suffer from PMDD. Efficacy with both doses 
affords greater flexibility to the prescribing physician.