Serotonin reuptake inhibitors for the treatment of premenstrual dysphoria

Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome, afflicting approximately 5% of all women of fertile age. The cardinal symptoms are irritability and anger. In addition, sadness, tension and carbohydrate craving are common complaints. The symptoms surface regularly between ovulation and menstruation, and disappear completely within a few days after the onset of the bleeding; in patients with remaining symptoms during the follicular phase, alternative diagnoses should be considered. In a large number of recent trials, serotonin reuptake inhibitors (clomipramine, citalopram, fluoxetine, paroxetine, sertraline) have been shown to reduce the symptoms of PMD much more effectively than placebo; in contrast, non-serotonergic antidepressants (maprotiline, bupropion) appear to be ineffective. Interestingly, the onset of action of clomipramine and selective serotonin reuptake inhibitors (SSRIs) is much shorter when used for PMD than when used for depression, panic disorder, or obsessive-compulsive disorder. Consequently, patients with PMD can restrict the medication to the luteal phase of the cycle. In a recent placebo-controlled trial, intermittent administration of the SSRI citalopram was shown to reduce the symptoms of PMD significantly better than placebo, but also better than continuous administration of the drug. A reasonable interpretation of the latter, unexpected finding is that continuous medication may be associated with a certain development of tolerance than can be avoided by intermittent drug administration. The observation that the symptoms of PMD may be effectively reduced by SSRIs is of considerable clinical importance since previously no effective treatment for this common condition - apart from those disrupting ovarian cyclicity - has been available. It is also of theoretical importance because it constitutes one of the first pharmacological observations supporting the concept that serotonin may dampen irritability and anger in humans.