Premenstrual Dysphoria and the Serotonin System: Pathophysiology and Treatment

The inclusion of research diagnostic criteria for premenstrual dysphoric disorder (PMDD) in theDSM-IV recognizes the fact that some women have extremely distressing emotional and behavioralsymptoms premenstrually. PMDD can be differentiated from premenstrual syndrome (PMS), whichpresents with milder physical symptoms, headache, and more minor mood changes. In addition,PMDD can be differentiated from premenstrual magnification of physical and/or psychological symptomsof a concurrent psychiatric and/or medical disorder. As many as 75% of women with regularmenstrual cycles experience some symptoms of PMS, according to epidemiologic surveys. PMDD ismuch less common; it affects only 3% to 8% of women in this group. The etiology of PMDD is largelyunknown, 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 andother target organs. The serotonergic system is in close reciprocal relationship with the gonadal hormonesand has been identified as the most plausible target for interventions. Thus, beyond the conservativetreatment 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 severalrandomized, placebo-controlled trials in women with PMDD have clearly demonstrated that theSRIs have excellent efficacy and minimal side effects. More recently, several preliminary studies indicatethat intermittent (premenstrual only) treatment with selective SRIs is equally effective in thesewomen and, thus, may offer an attractive treatment option for a disorder that is itself intermittent.