Antipsychotic drug clozapine can trigger severe obsessive-compulsive symptoms

A review published in the current issue of Psychotherapy and Psychosomatics analyzes the obsessions and compulsions associated with the use of clozapine, an antipsychotic drug,

It is not uncommon to find obsessive-compulsive symptoms (OCS) in patients treated with clozapine. These symptoms are attributed to anti-serotonergic effects of clozapine. The objective of this study was to conduct a systematic review of reported cases of clozapine-associated OCS to better understand the nature and management of these symptoms.

MEDLINE, Embase, and PsycINFO databases were searched with no publication year or language restrictions. Fifty-seven studiesreporting cases of clozapine-associated OCS, either de novo or exacerbation of preexisting OCS (107 cases total; 75 de novo, 32 exacerbated OCS) were included.
Results showed that clozapine triggered moderate-severe OCS at varying doses (100-900 mg/day) and treatment durations (median 6 months, interquartile range 2-24 months). Higher severity was significantly associated with preexisting OCS, poorer insight into OCS, and active psychosis at the time of OCS. Common strategies to treat clozapine-associated OCS included adding selective serotonin reuptake inhibitors, clomipramine, or aripiprazole, often accompanied by clozapine dose reduction. The rate of response to antidepressants was 49% (29/59), where younger age, shorter duration of underlying illness, shorter cloza­pine treatment duration, better insight into OCS, and presence of taboo thoughts were significantly associated with antidepressant response. Subsequent clozapine dose reduction was effective in many non-responders, where aripiprazole was simultaneously added in 50% (8/16).

These findings suggest that clozapine can trigger severe OCS. Adding aripiprazole with/without clozapine dose reduction may be a good alternative to antidepressants for managing clozapine-associated OCS. Clinicians should be more vigilant about these adverse effects and administer appropriate treatments.

Journal reference:

Kim, D.D., et al. (2020) Clozapine-Associated Obsessive-Compulsive Symptoms and Their Management: A Systematic Review and Analysis of 107 Reported Cases. Psychotherapy and Psychosomatics.


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