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
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.