Background: The safety and efficacy of fluoxetine in the short-term treatment of late luteal phase dysphoric disorder (LLPDD) have been shown in several studies, but its efficacy and safety over more than a few cycles have not been demonstrated.

Method: Sixty-four women with prospectively confirmed LLPDD were treated with fluoxetine for a mean of 18.6 months. Response was determined by clinical interview and Clinical Global Impressions rating within the first three cycles, and subjects were followed clinically every 3 to 6 months. Medication dose was titrated on the basis of side effects and response. Women who had been treated for at least 1 year were asked to discontinue medication to reassess the need for treatment.

Results: Sixty women were able to tolerate at least 1 month of treatment. Of these, 57% (N = 34) remained on 20 mg/day and 37% (N = 22) received 40 mg/day. Fifty-two percent (N = 31) achieved remission (CGI score = 1); 48% (N = 29) achieved a partial remission of symptoms (CGI score = 2). The most common side effect was sexual dysfunction, which occurred in 17% of women (N = 10). Symptoms recurred in most women after treatment discontinuation and remitted again with reinstitution of treatment. An earlier age at onset of LLPDD or a prior episode of major depression was associated with achieving only partial remission of symptoms.

Conclusion: These results support the findings of the double-blind studies of fluoxetine treatment for LLPDD. Fluoxetine is an effective and well-tolerated treatment for this condition when used over time. Approximately half of those treated achieved complete remission of their symptoms, while the others experienced significant improvement. This study also lends further support to the effectiveness of serotonergic agents in the treatment of premenstrual symptoms.