Autonomic responses of blood vessels and sweat glands in patients with schizophrenia treated with olanzapine or clozapine

Abstract.

Rationale: 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. Conclusion: 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 α₂-antagonistic effect of clozapine.