Immunomodulatory Effects of Psychotropic Drugs




Hinze-Selch, E.W. Becker, G. Stein, a. Schuld, T. Kraus, M.

Haack, and T. Pollmächer. Max-Planck-Institute of Psychiatry,

Munich, Germany

Malaria/fever therapy in the

beginning of this century gives early evidence for a link between

the immune system and psychiatric disorders. Chlorpromazine, the

first neuroleptic agent in clinical use, has antiparasitic and in

vitro immunomodulatory effects. Various in vitro and in vivo

peculiarities of the immune system have been described in

psychiatric disorders such as major depression and schizophrenia.

However, immunomodulatory properties of psychoactive drugs have

neither been investigated systematically nor considered

systematically in studies on the immune system of psychiatric


Therefore, we have been analyzing

in vivo and in vitro effects of psychoactive drugs on the immune

system of psychiatric patients and we have tried to link such

immunomodulatory effects to psychotrophic effects.

We found that the atypical

neuroleptic agent clozapine increases plasma levels of the

cytokines and soluble cytokine receptors TNF-a ,

sTNFRp55, sTNFRp75 and sIL-2r while in vitro immune variables

were affected in a complex way in the course of a 6 week

treatment with clozapine in schizophrenic patients1,2.

The class neuroleptic haloperidol does not have such effects3.

Whereas clozapine in patients and a non-pyrogenic dose of

endotoxin in healthy probands both increase stage 2 sleep the

immunologically non-active compound haloperidol increases stage 1

sleep4. However, the immunodulatory property is not

restricted to clozapine because the antidepressants ami-triptylin

and nortriptylin also increase plasma levels of both soluble

TNF-receptors in patients.

We conclude that some

psychoactive drugs have immunomodulatory effects whereas others

have not and that this property is independent of the

psychopharmacological characterization of the substances as

neuroleptics or antidepressants. As demonstrated for

polysomnographic nightsleep, a function regulated by the CNS,

such immunomodulation might even be involved in psychotrophic

effects. Therefore, we hypothesise that immunomodulation is a

considerable characteristic of a subgroup of psychoactive

substances and even predicts some psychoactive properties.

1 Pollmächer et al.

J. Clin Psychopharmacol 1996, 16:403-409

2Hinze-Selch et al.

Neuropsychpharmacology 1998, 19:114-122

3 Pollmächer et al.

Am J Psychiatry 1997, 154:1763-1765

4Hinze-Selch et al.

Biol Psychiatry 1997, 42:260-266