Neuroleptic reduction and/or cessation and neuroleptics as specific treatments for tardive dyskinesia

Abstract

Background: Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These drugs, however, have been also associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Various strategies have been examined to reduce a person's cumulative exposure to neuroleptics. These studies include dose reduction, intermittent dosing strategies, such as drug holidays, and neuroleptic cessation.

Objectives: To determine whether, for those people with both schizophrenia (or other chronic mental illnesses) and tardive dyskinesia (TD), a reduction or cessation of neuroleptic drugs was associated with reduction in TD symptoms. A secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for already established TD.

Search strategy: Electronic searches of Biological Abstracts (1982-1997), Cochrane Schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted.

Selection criteria: Reports were included if they assessed the treatment of neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illnesses and already established TD, who had been randomly allocated to (a) neuroleptic cessation (placebo or no intervention) versus neuroleptic maintenance; b. neuroleptic reduction (including intermittent strategies) versus neuroleptic maintenance; or c. specific neuroleptics for the treatment of TD versus placebo or no intervention.

Data collection and analysis: The reviewers extracted the data independently and the Odds Ratio (95% CI) or the average difference (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement.

Main results: Two trials were able to be included in this review. Sixty two were excluded and 16 are awaiting assessment. Seven trials are still pending classification. No randomised controlled trial-derived data were available to clarify the role of neuroleptics as treatments for TD. This includes the atypical antipsychotics including clozapine. Despite neuroleptic cessation being a frequently first-line recommendation, there were no RCT-derived data to support this. Two studies ( approximately approximately Cookson 1987 approximately approximately , approximately approximately Kane 1983 approximately approximately ) found a reduction in TD associated with neuroleptic reduction.

Reviewer's conclusions: The lack of evidence to support the efficacy of neuroleptic cessation as a treatment for TD, combined with the accumulating evidence of an increased risk of relapse should antipsychotic drugs be reduced, makes this intervention a hazardous treatment for TD. Dose reduction may offer some benefit as a treatment for TD compared to standard levels of neuroleptic use. There is a need to evaluate the utility of clozapine and the 'atypical' antipsychotics as treatments for established TD.