Premenstrual dysphoria and the serotonin system: pathophysiology and treatment

The inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in the DSM-IV recognizes the fact that some women have extremely distressing emotional and behavioral symptoms premenstrually. PMDD can be differentiated from premenstrual syndrome (PMS), which presents with milder physical symptoms, headache, and more minor mood changes. In addition, PMDD can be differentiated from premenstrual magnification of physical and/or psychological symptoms of a concurrent psychiatric and/or medical disorder. As many as 75% of women with regular menstrual cycles experience some symptoms of PMS, according to epidemiologic surveys. PMDD is much less common; it affects only 3% to 8% of women in this group. The etiology of PMDD is largely unknown, but the current consensus is that normal ovarian function (rather than hormone imbalance) is the cyclical trigger for PMDD-related biochemical events within the central nervous system and other target organs. The serotonergic system is in close reciprocal relationship with the gonadal hormones and has been identified as the most plausible target for interventions. Thus, beyond the conservative treatment options such as lifestyle and stress management, other nonantidepressant treatments, or the more extreme interventions that eliminate ovulation altogether, the serotonin reuptake inhibitors (SRIs) are emerging as the most effective treatment option for this population. Results from several randomized, placebo-controlled trials in women with PMDD have clearly demonstrated that the SRIs have excellent efficacy and minimal side effects. More recently, several preliminary studies indicate that intermittent (premenstrual only) treatment with selective SRIs is equally effective in these women and, thus, may offer an attractive treatment option for a disorder that is itself intermittent.