Clozapine withdrawal effects and receptor profiles of typical and atypical neuroleptics

Cherian Verghese, Jose DeLeon, Chand Nair, George M. Simpson

Research output: Contribution to journalComment/debate

62 Scopus citations


Withdrawal effects of neuroleptics have not received much attention. Clozapine withdrawal phenomena have been attributed to psychosis arising from D2 supersensitivity, which is unlikely since it has minimal action on D2 receptors. The time course and clinical features of this phenomenon suggest that cholinergic overdrive and gamma-aminobutyric acid (GABA) supersensitivity occurs after withdrawal, since it is strongly anticholinergic and has a GABAergic action. Recently, a number of patients showed marked decompensation when they were switched from clozapine to risperidone, especially when they were rapidly tapered off clozapine. This was probably more due to withdrawal effects than the primary psychosis or a lack of efficacy of risperidone. A slow withdrawal schedule would facilitate homeostatic mechanisms; anticholinergics would be useful in clozapine withdrawal. This area has not received any attention from researchers, nor are there any guidelines for clinicians. This will be particularly important with the widespread use of atypical agents in the future.

Original languageEnglish
Pages (from-to)135-138
Number of pages4
JournalBiological Psychiatry
Issue number2
StatePublished - Jan 15 1996


  • Anticholinergics
  • Clozapine
  • Dopamine receptors
  • Neuroleptics
  • Risperidone
  • Substance withdrawal syndrome

ASJC Scopus subject areas

  • Biological Psychiatry


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