Research into the psychobiology of premenstrual dysphoric disorder (PDD) finds 
alterations in markers associated with serotonergic neurotransmission. 
Supporting this is work showing that patients with PDD respond to some agents 
that block the reuptake of serotonin. In this open trial, patients were treated 
for one cycle with placebo and then for three consecutive cycles with the 
serotonin reuptake inhibitor paroxetine. The study population was composed of 14 
participants who met DSM-IV criteria for PDD with moderate to severe 
symptomatology and specifically endorsed anger and irritability as a central 
premenstrual complaint. Patients showed modest improvement over the course of 
the pretreatment evaluation, with significant improvement occurring for feelings 
of worthlessness, decreased interest, and low energy. The effects of active 
treatment were marked by the first active cycle with luteal phase 17-item 
Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 
8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in 
the third active treatment cycles (F[1,13] = 17.6; p < 0.0001). A group of items 
from daily ratings indicative of anger and irritability (mood swings, anger and 
irritability, behavioral dyscontrol, and interpersonal conflicts) also showed 
improvement (F[1,13] = 5.94; p < 0.03). Various definitions of response were 
applied to treatment completers. The most conservative measure, the Clinical 
Global Impression (CGI), revealed that 7 of 14 patients had a complete response 
(CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3). These open 
trial findings are consistent with the notion that paroxetine is effective in 
the acute phase for the treatment of PDD.