Background: It is commonly recommended that a switch to clozapine be implemented in the face of tardive dyskinesia, even if current treatment involves another "atypical" agent. However, reports do indicate clozapine carries a liability for tardive dyskinesia.
Aims: This review sought to evaluate clozapine in relation to tardive dyskinesia in the context of available evidence.
Methods: Medline, Embase, and PsycINFO databases were searched for studies published in English, using the keywords: clozapine AND tardive dyskinesia OR TD. References from major review articles were searched for additional relevant publications. Studies were included if they investigated: tardive dyskinesia in clozapine-treated patients diagnosed with schizophrenia spectrum disorders, and reported on two or more assessments of tardive dyskinesia severity measured by the Abnormal Involuntary Movement Scale; or clozapine's tardive dyskinesia liability.
Results: In total, 513 unique citations were identified and 29 reports met the inclusion criteria. Thirteen studies suggest clozapine reduces dyskinetic symptoms over time (n=905 clozapine-treated participants); however, the minimum required dose and effect of withdrawal requires further investigation. The majority of reports which address clozapine's liability for tardive dyskinesia are case studies (11 of 14 reports, 79%), and clozapine was only the first-line treatment in one of the remaining three studies reporting treatment-emergent dyskinetic symptoms with clozapine in 12% of patients. No significant between-drug differences were identified comparing clozapine's risk to other atypical antipsychotics.
Conclusions: Research to date supports switching to clozapine for the purpose of reducing tardive dyskinesia risk and/or treating existing tardive dyskinesia, but prospective randomized controlled trials are necessary if we are to substantiate existing recommendations.
Keywords: Schizophrenia; antipsychotics; clozapine; extrapyramidal symptoms; tardive dyskinesia.