Review of withdrawal catatonia: what does this reveal about clozapine?

Matthew Lander; Tarun Bastiampillai; Jitender Sareen

doi:10.1038/s41398-018-0192-9

Review of withdrawal catatonia: what does this reveal about clozapine?

Transl Psychiatry. 2018 Jul 31;8(1):139. doi: 10.1038/s41398-018-0192-9.

Authors

Matthew Lander¹, Tarun Bastiampillai^{2

3}, Jitender Sareen⁴

Affiliations

¹ Department of Psychiatry, University of Manitoba, Winnipeg, Canada. mlander2@exchange.hsc.mb.ca.
² Discipline of Psychiatry, School of Medicine, Flinders University, Adelaide, Australia.
³ South Australian Health and Medical Research Institute, Adelaide, Australia.
⁴ Departments of Psychiatry, Psychology, and Community Health Sciences, University of Manitoba, Winnipeg, Canada.

Abstract

Withdrawal symptoms are common upon discontinuation of psychiatric medications. Catatonia, a neuropsychiatric condition proposed to be associated with gamma-aminobutyric acid (GABA) hypoactivity due to its robust response to benzodiazepines, has been described as a withdrawal syndrome in case reports but is not a well-recognized phenomenon. The authors undertook a review of withdrawal catatonia with an aim to understand its presentation as well as the medications and psychoactive substances it is associated with. The review identified 55 cases of withdrawal catatonia, the majority of which occurred upon discontinuation of benzodiazepines (24 cases) and discontinuation of clozapine (20 cases). No other antipsychotic medications were identified as having been associated with the onset of a catatonic episode within 2 weeks following their discontinuation. Increasing GABA activity and resultant GABA receptor adaptations with prolonged use is postulated as a shared pharmacological mechanism between clozapine and benzodiazepines that underlie their association with withdrawal catatonia. The existing evidence for clozapine's activity on the GABA system is reviewed. The clinical presentations of benzodiazepine withdrawal catatonia and clozapine withdrawal catatonia appear to differ and reasons for this are explored. One reason is that benzodiazepines act directly on GABA_A receptors as allosteric agonists, while clozapine has more complex and indirect interactions, primarily through effects on receptors located on GABA interneurons. Another possible reason for the difference in clinical presentation is that clozapine withdrawal catatonia may also involve receptor adaptations in non-GABA receptors such as dopamine and acetylcholine. The findings from our review have implications for the treatment of withdrawal catatonia, and treatment recommendations are provided. Further research understanding the uniqueness of clozapine withdrawal catatonia among antipsychotic medication may give some insight as to clozapine's differential mechanism of action.

Publication types

Review

MeSH terms

Benzodiazepines / adverse effects*
Catatonia / chemically induced*
Clozapine / adverse effects*
GABA Antagonists / adverse effects*
Humans
Substance Withdrawal Syndrome / diagnosis*

Substances

GABA Antagonists
Benzodiazepines
Clozapine