Clozapine Monotherapy Improves Antipsychotic-Induced Tardive Dyskinesia

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There was a slight reduction in symptoms of tardive dyskinesia and the most benefit was observed in patients with moderate to severe tardive dyskinesia.

For most patients, treatment with clozapine can produce a slight reduction in the antipsychotic-induced movement disorder tardive dyskinesia and can greatly reduce the disorder’s severity in patients with moderate to severe cases, according to a study published in The Journal of Clinical Psychiatry.

This metanalysis included 17 studies published in English and Dutch found through Embase, PsycINFO, and PubMed up until October 13, 2015. Criteria for inclusion were schizophrenia or related disorder diagnosis, a switch from an alternate antipsychotic/s to clozapine monotherapy, and available data on a tardive dyskinesia rating scale before and after the medication switch. Independent investigators extracted the data, which were analyzed in a random-effects model after being converted to standardized mean value change scores.

For patients with subclinical tardive dyskinesia (13 studies), there was no significant difference seen after switching to clozapine (n=1012; standardized mean change=−0.21; ES 95% CI, −0.44 to 0.01; P =.06). However, 3 of the 12 studies are clear outliers, and an analysis of the other 9 studies alone does show an effect (n=830; standardized mean change=−0.33; ES 95% CI, −0.42 to −0.24; P <.01). When all the studies were taken together, overall results showed that switching to clozapine produced a significant reduction in tardive dyskinesia (n=1060; standardized mean change=-0.40; P <.01), particularly in the 4 studies that focused on tardive dyskinesia severity as a primary outcome (n=48; standardized mean change=−2.56; 95% CI, −4.85 to –0.28; P =.02).

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Study investigators conclude that these findings indicate “that there is now sufficient evidence that moderate to severe [tardive dyskinesia] and/or substantial discomfort due to [tardive dyskinesia] may be considered as an indication for switching antipsychotic to clozapine in clinical guidelines.”


Mentzel TQ, van der Snoek R, Lieverse R, et al. Clozapine monotherapy as a treatment for antipsychotic-induced tardive dyskinesia: a meta-analysisJ Clin Psychiatry. 2018; 79(6).