Clozapine-olanzapine: a potentially dangerous switch. A report of two cases

Withdrawal symptoms associated with switch between two typical antipsychotics are generally rare and mild. In contrast, switching from clozapine to risperidone can be lead to severe withdrawal symptoms. Different pathophysiologic aetiologies have been suggested for explaining these severe symptoms, including cholinergic supersensitivity and rebound. Theoretically, the switch from clozapine to olanzapine should not lead to any problems because those two agents have the same affinity in vitro for muscarinic receptors.

This study reports two cases of switches from clozapine to olanzapine, in refractory schizophrenic patients, which were associated with severe withdrawal symptoms.

After the switch, the two patients developed diaphoresis, hypersialorrhea, bronchial obstruction, agitation, anxiety and enuresis. The symptoms were treated with anticholinergic medication and by an increase in dose of olanzapine to 20 mg/day. For one of the patients this treatment led to normalization of secretion. For the other patient, a superinfection leading to a bilateral pneumopathy which required emergency hospitalization in a general hospital was observed.

The symptomatology and the response to treatment lead to the hypothesis of a muscarinic from abrupt weaning. The withdrawal symptoms disappeared rapidly with an increase in olanzapine dosage and with anticholinergic started at the beginning of the switch. We recommend slow clozapine weaning over 3 weeks or more with concurrent anticholinergic treatment.