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

The aim of this study was to investigate for the effects of valpromide on h eart rate circadian rhythm in remitted recurrent unipolar and bipolar disor ders (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 cri teria comprised motor activity (MA) and the Bech and Rafaelsen mania assess ment scale, Horne and Ostberg questionnaire, Montgomery and Asberg depressi on 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, evalu ation of the quality of sleep by patients themselves showed valpromide to b e superior to placebo (P = 0.045, one-tailed test). The results of analysis of the Spiegel questionnaire also confirm the superiority of valpromide ov er placebo. Safety and compliance were comparable for the active drug and the placebo. In conclusion, the relatively small sample size requires cautious interpret ation of this study. Nevertheless, these initial results show a definite ef fect of valpromide on a biological rhythm that leads one to suppose that it may be effective through a 'synchronizing' effect. (C) 2000 Editions scien tifiques et medicales Elsevier SAS.