Withdrawal from clozapine: The "rebound phenomenon"

Clozapine is an "atypical" antipsychotic agent for treating previously resi stant schizophrenic patients. Its main advantages over "typical" neurolepti cs are low incidence of extrapyramidal side effects and its capacity to ind uce therapeutic response in previously treated refractory patients. However , withdrawal from clozapine has been observed to lead to "atypical" clinica l characteristics or a "rebound phenomenon," manifested in two interwoven c linical forms: (1) psychotic exacerbation, and (2) cholinergic rebound. The underlying pathophysiological mechanism of this phenomenon is postulated t o be a result of cholinergic supersensitivity. In this paper, the "rebound phenomenon" will be discussed and exemplified by three case histories in wh ich abrupt cessation of clozapine led to serious deterioration and psychoti c exacerbation, and one case in which gradual titration from the drug was e mployed in order to preempt this hazardous occurrence.