Clozapine withdrawal resulting in delirium with psychosis: a report of three cases.
BACKGROUND
Withdrawal symptoms for typical antipsychotics are generally mild, self-limited and do not include development of psychotic symptoms. In contrast, withdrawal symptoms for clozapine can be severe with rapid onset of agitation, abnormal movements, and psychotic symptoms. Different pathophysiologic etiologies have been suggested for these severe symptoms, including dopaminergic supersensitivity and rebound.


METHODS
Three case reports of clozapine withdrawal symptoms are presented. A review of previous case reports and discussion of the etiology of withdrawal symptoms of typical antipsychotics and clozapine are provided.


RESULTS
These three patients developed delirium with psychotic symptoms that resolved rapidly and completely upon resumption of low doses of clozapine.


CONCLUSIONS
The severe agitation and psychotic symptoms after clozapine withdrawal in these three patients were due to delirium, perhaps the result of central cholinergic rebound. The withdrawal symptoms and delirium resolved rapidly with resumption of low doses of clozapine. Severe withdrawal symptoms can probably be avoided by slowly tapering clozapine and/or simultaneously substituting another psychotropic with high anticholinergic activity, such as thioridazine.
Stanilla
J K
JK
Department of Psychiatry, Allegheny University, Norristown State Hospital, Pa. 19401, USA.
de Leon
J
J
Simpson
G M
GM
D000328:Adult; D003024:Clozapine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D003693:Delirium / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D011605:Psychoses, Substance-Induced / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D011618:Psychotic Disorders / Q000188:drug therapy; D011954:Receptors, Dopamine / Q000502:physiology; D012008:Recurrence; D012559:Schizophrenia / Q000139:chemically induced / Q000188:drug therapy*; D012563:Schizophrenia, Paranoid / Q000188:drug therapy; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D013881:Thioridazine / Q000627:therapeutic use
D011954:Receptors, Dopamine; D003024:Clozapine; D013881:Thioridazine; D004298:Dopamine