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In a previous controlled trial we have shown that premenstrual irritability and depressed mood (premenstrual syndrome) can be effectively reduced by low doses of the potent (but nonselective) serotonin reuptake inhibitor clomipramine taken each day of the menstrual cycle. The present study was undertaken to examine to what extent intermittent administration of clomipramine, during the luteal phase only, is also effective against premenstrual complaints. Twenty-nine nondepressed women displaying severe premenstrual irritability and/or depressed mood and fulfilling the DSM-III-R criteria of late luteal phase dysphoric disorder were treated daily from the day of ovulation until the onset of the menstruation either with clomipramine (25 to 75 mg) (n = 15) or with placebo (n = 14) for three consecutive menstrual cycles; another nine subjects (seven on clomipramine, two on placebo) dropped out during treatment. In both treatment groups self-rated premenstrual irritability and depressed mood (as registered daily using a visual analogue scale) were significantly reduced during treatment; in the placebo group, this symptom reduction was about 45%, whereas in the clomipramine group it was greater than 70%. The mean premenstrual ratings of irritability and depressed mood during the three treatment cycles were significantly lower in the clomipramine group than in the placebo group. Also with respect to the rating of global improvement, the result obtained with clomipramine was significantly better than that obtained with placebo. The study confirms the previously reported effectiveness of low doses of clomipramine in the treatment of premenstrual syndrome and demonstrates that the time lag between onset of medication and clinical effect is shorter when clomipramine is used for premenstrual syndrome than when it is used for depression, panic disorder, or obsessive compulsive disorder.

Clomipramine Administered during the Luteal Phase Reduces the Symptoms of Premenstrual Syndrome: A Placebo-Controlled Trial