Valpromide increases amplitude of heart rate circadian rhythm in remitted bipolar and unipolar disorders.A placebo-controlled study

Abstract

The aim of this study was to investigate for the effects of valpromide on heart rate circadian rhythm in remitted recurrent unipolar and bipolar disorders (DSM-III-R). It consisted of a comparative, randomized, double-blind, repeated cross-over study of valpromide versus placebo over four four-week periods. The primary evaluation criteria was heart rate (HR). Secondary criteria comprised motor activity (MA) and the Bech and Rafaelsen mania assessment scale, Horne and Ostberg questionnaire, Montgomery and Asberg depression rating scale, Spiegel questionnaire, a sleep diary, and Clinical Global Impression. Fifteen patients were included, giving 60 one-month periods (30 valpromide periods and 30 placebo periods).Cosinor analysis of HR and MA data revealed a difference in amplitude (P = 0.037, analysis of variance, one-tailed test).The clinical sleep study shows that the duration of sleep was greater with valpromide than with placebo (P = 0.007, one-tailed test). Similarly, evaluation of the quality of sleep by patients themselves showed valpromide to be superior to placebo (P = 0.045, one-tailed test). The results of analysis of the Spiegel questionnaire also confirm the superiority of valpromide over placebo. Safety and compliance were comparable for the active drug and the placebo.In conclusion, the relatively small sample size requires cautious interpretation of this study. Nevertheless, these initial results show a definite effect of valpromide on a biological rhythm that leads one to suppose that it may be effective through a ‘synchronizing’ effect.