Venlafaxine in the treatment of premenstrual dysphoric disorder

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine, a new-genera tion antidepressant that selectively inhibits serotonin and norepinephrine reuptake, in the treatment of premenstrual dysphoric disorder (PMDD). METHOD: We conducted a randomized, double-blind, placebo-controlled, parall el-group, flexible-dose trial. After three screening cycles, including a si ngle-blind placebo cycle, 164 women were randomly assigned to double-blind treatment with venlafaxine (50-200 mg/day) or placebo for four menstrual cy cles. Primary outcome measures were the total premenstrual symptom scores a s assessed by a daily symptom report (DSR) and the Hamilton Rating Scale fo r Depression. RESULTS: Venlafaxine was significantly more effective than placebo in reduc ing PMDD symptoms as assessed by DSR scores (P < .001 for last observation carried forward and observed analyses). Sixty percent of venlafaxine versus 35% of placebo subjects improved >50% (P = .003). Forty-three percent of v enlafaxine subjects versus 25% of placebo subjects experienced symptom remi ssion, defined as reduction of DSR scores to the postmenstrual level (P = . 034). Venlafaxine treatment was significantly better than placebo for all s tatistically derived DSR factors (mood, function, pain, and physical sympto ms). Improvement was relatively swift, with approximately 80% symptom reduc tion in the first treatment cycle. Mean venlafaxine doses ranged from 50 mg /day in the first treatment cycle to 130 mg/day in the fourth treatment cyc le. Adverse events such as nausea, insomnia, and dizziness were mild and tr ansient. CONCLUSIONS: Venlafaxine is significantly more efficacious than placebo for PMDD treatment. Response to treatment can occur in the first treatment cyc le, and venlafaxine is well tolerated. Further studies are needed to evalua te the potential of intermittent (luteal phase) dosing for this cyclic diso rder and the efficacy of long-term maintenance treatment with venlafaxine. (Obstet Gynecol 2001;98:737-44. (C) 2001 by the American College of Obstetr icians and Gynecologists).