1. ¹Department of Clinical Neuroscience, Section of Psychiatry S:t Göran, Karolinska Institutet, Stockholm, Sweden
2. ²Department of Gynaecology and Obstetrics, Göteborg University, Göteborg, Sweden
3. ³Department of Medicine and Care, Division of Clinical Pharmacology, Linköping University, Linköping, Sweden
4. ⁴Department of Pharmacology, Institute of Neuroscience and Physiology, Göteborg University, Göteborg, Sweden

Correspondence: Dr Mikael Landén, Department of Clinical Neuroscience, Section of Psychiatry S:t Göran, Karolinska Institutet, SE 112 81 Stockholm, Sweden, Tel: +46 (8) 672 23 71, Fax: +46 (8) 672 19 08, E-mail: mikael.landen@cns.ki.se

Received 10 December 2007; Revised 27 April 2008; Accepted 8 May 2008; Published online 2 July 2008.

Abstract

Several studies suggest that serotonin reuptake inhibitors (SRIs) exert a more rapid effect when used for the treatment of symptoms such as anger and irritability then when used for depression, obsessive-compulsive disorder, or anxiety. In line with this, premenstrual irritability can be effectively dampened by intermittent administration of an SRI, from ovulation to menstruation, indicating an onset of action of 10 days or less. How fast this effect appears, in terms of hours or days, is of considerable theoretical interest, but has previously not been studied in detail. To explore this issue, 22 women with marked premenstrual irritability, who previously had responded to paroxetine, were given this compound during two menstrual cycles and placebo during one cycle in a double-blind, cross-over fashion. The women were asked to start medication in the midst of the luteal phase when irritability had been intense for 2 days. The paroxetine cycles differed significantly from the placebo cycle as early as 14 h after drug intake with respect to the number of subjects experiencing sustained reduction in irritability. When the different cycles were compared with respect to irritability-rating scores for each time of assessment, the difference was significant at day 3. The side effect nausea had an even more rapid onset (4 h), but usually disappeared within 4 days. To summarize, this controlled trial shows that an SRI reduces premenstrual irritability already within a few days after the onset of treatment.