Nefazodone in the treatment of premenstrual syndrome: a preliminary study.

Nefazodone, a new phenylpiperazine antidepressant agent with serotonin type 2 antagonism and serotonin reuptake inhibition, was evaluated in two patient groups to determine its effectiveness in reducing the symptoms of premenstrual syndrome (PMS). The two studied groups were PMS patients with no coexisting major depression or dysthymia (N = 23) and PMS patients with current major depression or dysthymia, termed the premenstrual exacerbation group (N = 24). The two patient groups received open-label nefazodone for 8 weeks, with optional maintenance at the same dose for up to 1 year. The initial dose was 100 mg, titrated to 600 mg/day, on a twice-daily dosing schedule. Symptoms were assessed by the Hamilton Rating Scale for Depression and by Daily Symptom Ratings. Premenstrual symptoms improved significantly from pretreatment baseline values, with similar improvement for the PMS and premenstrual exacerbation groups. Significantly improvement occurred by the end of the first treated cycle (4 weeks of therapy), at an average dose of 245 (range, 100 to 400) mg, and was maintained thereafter. Nefazodone was well tolerated, side effects were often transient, and the most common were nausea and headache. Forty-seven of 54 patients completed 2 months of therapy, with a mean daily nefazodone dose of 319 mg at the 2-month point. A placebo-controlled study should be conducted to confirm and extend these promising preliminary findings.