Influences of biological rhythms on the effects of psychotropic drugs.

The efficacy of psychotropic drugs varies depending on the time of administration. This phenomenon is observed with antipsychotics, antidepressants, mood stabilizers, benzodiazepines, barbiturates, and psychostimulants. The presence or absence of this phenomenon and the rhythm phase in the efficacy of each drug varies depending on the drug, dose, parameter measured, animal species, and strain. A recent study demonstrating circannual changes in the phases of circadian rhythm of drug efficacy suggests that discrepancies between studies may be considerably explained by the presence of a circannual rhythm. The rhythms in drug effects are suggested not to be due to rhythmic changes in the pharmacokinetics of the drugs but rather to an endogenous rhythm in drug susceptibility resulting from a circadian rhythm in the intracerebral neurotransmission system. The presence of this phenomenon and its law have been demonstrated to a considerable extent in animals, but corresponding clinical reports in humans remain insufficient despite its clinical importance. Further study in humans is certainly warranted.