Fluoxetine's spectrum of action in premenstrual syndrome

This study extends our previous report of the efficacy and tolerability of fluoxetine in severe premenstrual syndrome (PMS), describes which aspects of the disorder are responsive to such treatment, and assesses the relationship between steady-state drug level and clinical outcome. Twenty-one women with documented PMS satisfied criteria for late luteal phase dysphoric disorder (DSM-III-R) and accepted the offer of a double-blind, randomized crossover trial of fluoxetine hydrochloride 20 mg/day vs placebo. Symptom severity was measured with daily self-rating, monthly premenstrual assessment forms and psychiatric interviews after 3 months each of baseline, placebo and fluoxetine treatment. Compared with an inconsistent placebo response, fluoxetine produced marked improvement in 15 of 16 women completing the trial, eight showing virtually complete remission of PMS symptoms. Fluoxetine's efficacy extended over a range of affective, physical and behavioural symptoms; its superiority obtained whether it preceded or followed placebo. Three women withdrew due to adverse effects of fluoxetine, and 10 of 16 completing the trial reported at least one adverse effect of this agent. Compared with placebo, fluoxetine produced more (but usually transient) insomnia, sweating, gastrointestinal and menstrual disturbance. Plasma levels of fluoxetine and its active metabolite were not reliably associated with efficacy nor with side effects. Serotonergic agents appear to have considerable promise in treating a range of symptoms in women with severe PMS.