Autonomic responses of blood vessels and sweat glands in patients with schizophrenia treated with olanzapine or clozapine.
BACKGROUND
Data comparing the in vivo effects on autonomic nervous system function of standard clinical doses of olanzapine and clozapine are sparse.


OBJECTIVE
The goal of this study was to compare the skin conductance response (which is peripherally mediated via muscarinic m3-receptors) and the inspiratory gasp response (which is peripherally mediated via adrenergic receptors) between healthy controls and schizophrenics treated with clozapine or olanzapine.


METHODS
Twenty patients with schizophrenia (according to DSM-III-R criteria) treated with either clozapine (200-500 mg/day) or olanzapine (10-20 mg/day) as well as ten matched controls underwent simultaneous recordings of the skin conductance response (SCR) of sweat glands and of the inspiratory gasp response (IGR) of acral blood vessels. A single, deep inspiration was used as the stimulus. Group differences for the SCR amplitudes and the post-IGR redilation times were compared using the Mann-Whitney test.


RESULTS
Both clozapine- and olanzapine-treated patients showed a significant SCR reduction compared to controls. Interestingly, the reduction in SCR was significantly larger in the clozapine group compared to the olanzapine group (P<0.05). Moreover, only clozapine-treated patients showed a statistical trend towards a longer IGR redilation time compared to controls.


CONCLUSIONS
The significantly stronger SCR reduction amongst clozapine-treated compared to olanzapine-treated patients suggests that olanzapine at a standard clinical dose exhibits a significantly smaller anticholinergic effect at peripheral m3-receptors in vivo compared to clozapine. The prolongation of IGR redilation can be explained by a prolonged release of noradrenaline due to the alpha2-antagonistic effect of clozapine.
Mueck-Weymann
M
M
Institute of Physiology and Cardiology, University of Erlangen-Nürnberg, Waldstr. 6, 91054 Erlangen, Germany. michael.mueck@web.de
Acker
J
J
Agelink
M W
MW
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001569:Benzodiazepines; D001808:Blood Vessels / Q000187:drug effects* / Q000294:innervation; D003024:Clozapine / Q000009:adverse effects*; D005260:Female; D005712:Galvanic Skin Response / Q000187:drug effects; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D012039:Regional Blood Flow / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D012867:Skin / Q000098:blood supply; D013545:Sweat Glands / Q000187:drug effects* / Q000294:innervation
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D000077152:Olanzapine