Clomipramine effectively reduces premenstrual irritability and dysphoria: a placebo‐controlled trial

Forty nondepressed women displaying severe premenstrual irritability and/or dysphoria and fulfilling the DSM-III-R criteria of late luteal phase dysphoric disorder were treated daily for 3 menstrual cycles with either the potent serotonin reuptake inhibitor clomipramine (25-75 mg; flexible dosage) (n = 20) or placebo (n = 20). In both treatment groups premenstrual irritability and dysphoria (as rated daily by the patients using a visual analogue scale) were significantly reduced as compared with the rating during 2 pretreatment reference cycles; however, in the placebo group this reduction was only about 40% whereas, in the clomipramine group, the symptom decrease was greater than 80%. At all 3 treatment cycles, patients on clomipramine displayed significantly lower symptom rating than controls. Also with respect to the rating of global improvement, the results obtained with clomipramine were considerably and significantly better than those obtained with placebo. It is concluded that low doses of clomipramine effectively reduce premenstrual irritability and dysphoria with a response rate close to 100%. The possible role of serotonin in the pathophysiology of the premenstrual syndrome is discussed.