Sleep changes following chlorpromazine, clozapine, olanzapine or thalidomide in healthy subjects – First results from a double-blind, placebocontrolled study

Different sedative psychotropic substances do not only exert effects on central nervous neurotransmitter systems, but also have immunmodulatory properties, which might contribute to their pharmacodynamic properties.

We examined in 40 healthy subjects the effects of two different dosages of chlorpromazine, clozapine, olanzapine and thalidomide on sleep in a double-blind, placebo-controlled experiment. All these psychotropic drugs have been observed to exert different effects on immune parameters.

In the present study all drugs had comparable sedative properties, but induced differential effects on sleep architecture: Clozapine-intake reduced REM-sleep, which was increased following chlorpromazine-intake. All substances increased nonREM-sleep, slow wave sleep was reduced following clozapine, but increased following olanzapine.

These differential effects on sleep architecture might be due to the different immunomodulatory effects expecially on cyokines of the TNF-system, which are known to be pivotally involved in sleep regulation: A more robust activation like during clozapine therapy suppresses REM- and slow wave sleep, whereas a more subtle activation increases slow wave sleep.