Clozapine and tardive dyskinesia in patients with schizophrenia: A systematic review

Abstract

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.

An evaluation of the variation and underuse of clozapine in the United Kingdom

“…21 Nevertheless, it has beneficial effects in reversing the severe neurological adverse effect, Tardive Dyskinesia (TD) caused by other antipsychotics. 22 Also, the significant interindividual differences in clozapine kinetics and challenges in use during pregnancy are additional difficulties. 23 Patients of African ancestry are especially disadvantaged with respect to clozapine utilisation, being less likely to be initiated on, and more likely to discontinue, treatment.…”

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

“…The importance of well-being during pharmacotherapy is receiving more and more attention [129] and is particularly relevant in explaining the high adherence of some patients to clozapine, demonstrated by the lower discontinuation rates in cohort studies [127,128]. Clozapine positive effects on well-being in some patients may be influenced by clozapine effects on extrapyramidal symptoms [130][131][132][133][134][135][136][137][138][139][140][141][142], hostility [143,144] and the "awakening" phenomenon [145][146][147] (online suppl. Box S5, section 3).…”

Continuous versus extended antipsychotic dosing in schizophrenia: Less is more

“…Interestingly, the fast koff property of atypicals could explain why they are generally less likely than typical antipsychotic drugs to produce dopaminedependent side effects. For instance, compared to typical antipsychotics, clozapine is unlikely to produce tardive dyskinesia and can in fact improve tardive dyskinesia caused by other antipsychotic agents [61]. Other atypical antipsychotic drugs-including the D2 antagonists risperidone, olanzapine and quetiapine and the D2 partial agonist aripiprazole-are also thought to be less likely to produce tardive dyskinesia when compared to typicals [62][63][64][65].…”