Clozapine Monotherapy May Be Effective in Reducing the Severity of Antipsychotic-Induced Tardive Dyskinesia

tardive dyskinesia
tardive dyskinesia
These results provide support for switching antipsychotics to clozapine in patients with moderate to severe tardive dyskinesia.

Clozapine monotherapy may be effective treatment for antipsychotic-induced tardive dyskinesia (TD), per the results of a meta-analysis published in the Journal of Clinical Psychiatry.

Investigators separately conducted 2 systematic searches using Embase, MEDLINE, and PsycINFO for the keywords “clozapine” and “tardive dyskinesia.” Inclusion criteria restricted articles to those involving patients with schizophrenia who had switched their medication to monotherapy with clozapine. Each study was also required to assess TD in patients on a rating scale at least once prior and once after switching to clozapine. Researchers extracted patient demographic data, information on clozapine treatment, TD scale scores, and schizophrenia symptom scale scores. As a primary outcome, investigators captured TD scale score changes after clozapine therapy. A random-effects model was used to assess correlations given the high heterogeneity between studies.

Of 283 articles identified per original search terms, 17 met all inclusion criteria and were investigated in the meta-analysis. Studies that investigated clozapine monotherapy as a treatment for patients with clinical levels of TD were labeled the clinical TD group (n=4). The remaining studies investigated TD as a secondary outcome, and their study populations had no to mild TD (n=13). The majority of studies (n=14) measured the severity of TD on the Abnormal Involuntary Movement Scale. For patients in the clinical TD group, a significant reduction in TD severity was observed after switching to clozapine (raw mean Abnormal Involuntary Movement Scale change, −10.64; P <.01). A significant reduction was also observed across all studies (P <.01). After pooling the studies that used the Abnormal Involuntary Movement Scale as a TD measure, a reduction in severity was also observed (raw mean change, −3.00; P =.01).

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The overall random-effects model indicates a slight reduction in TD after clozapine monotherapy across all studies. However, the effect was most significant among those with clinical TD. Even among studies of patients with subclinical TD, clozapine very rarely worsened TD and was associated with a slight reduction in TD severity. Further research should investigate the effectiveness of clozapine in larger populations of patients with antipsychotic-induced clinical TD. These results provide support for switching antipsychotics to clozapine in patients with moderate to severe TD.


Mentzel TQ, van der Snoek R, Lieverse R, et al. Clozapine monotherapy as a treatment for antipsychotic-induced tardive dyskinesia: a meta-analysis. J Clin Psychiatry. 2018;79(6):17r11852.