Can severe cardiorespiratory dysregulation induced by clozapine monotherapy be predicted?

Severe orthostatic and cardiorespiratory dysregulation may occur during institution of clozapine therapy both during concomitant benzodiazepine medication and on reinstitution of clozapine after a washout period. Extensive medical and neurological workup before and after the trials can nevertheless be normal. The absence of similar previous reactions to other drugs, adhering to monotherapy with clozapine, increasing dosage slowly or performing a single test for orthostatic reactions after initiating clozapine are insufficient precautionary measures. Cardiorespiratory complications can occur without the challenge of assuming an erect position but appear to otherwise run an initial course similar to that of severe orthostatic reactions. A significantly abnormal response to testing for orthostatic reactions may be established, but only during the period of vulnerability to cardiorespiratory dysregulation. Repeated testing for this predisposition during the first weeks of clozapine therapy is suggested.