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Meta-Analysis
. 2018 Jan 17;1(1):CD000204.
doi: 10.1002/14651858.CD000204.pub2.

Anticholinergic medication for antipsychotic-induced tardive dyskinesia

Hanna Bergman  1 , Karla Soares-Weiser
Affiliations
Meta-Analysis

Anticholinergic medication for antipsychotic-induced tardive dyskinesia

Hanna Bergman et al. Cochrane Database Syst Rev. .

Abstract

Background: Antipsychotic (neuroleptic) medication is used extensively to treat people with serious mental illnesses. However, it is associated with a wide range of adverse effects, including movement disorders. Because of this, many people treated with antipsychotic medication also receive anticholinergic drugs in order to reduce some of the associated movement side-effects. However, there is also a suggestion from animal experiments that the chronic administration of anticholinergics could cause tardive dyskinesia.

Objectives: To determine whether the use or the withdrawal of anticholinergic drugs (benzhexol, benztropine, biperiden, orphenadrine, procyclidine, scopolamine, or trihexylphenidyl) are clinically effective for the treatment of people with both antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illnesses.

Search methods: We retrieved 712 references from searching the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (16 July 2015 and 26 April 2017). We also inspected references of all identified studies for further trials and contacted authors of trials for additional information.

Selection criteria: We included reports identified in the search if they were controlled trials dealing with people with antipsychotic-induced tardive dyskinesia and schizophrenia or other chronic mental illness who had been randomly allocated to (a) anticholinergic medication versus placebo (or no intervention), (b) anticholinergic medication versus any other intervention for the treatment of tardive dyskinesia, or (c) withdrawal of anticholinergic medication versus continuation of anticholinergic medication.

Data collection and analysis: We independently extracted data from included trials and we estimated risk ratios (RR) with 95% confidence intervals (CIs). We assumed that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.

Main results: The previous version of this review included no trials. We identified two trials that could be included from the 2015 and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in the USA and Germany. Overall, the risk of bias was unclear, mainly due to poor reporting: allocation concealment was not described; generation of the sequence was not explicit; studies were not clearly blinded; and outcome data were not fully reported.Findings were sparse. One study reported on the primary outcomes and found that significantly more participants allocated to procyclidine (anticholinergic) had not improved to a clinically important extent compared with those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1 RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that there was no evidence of a difference in the incidence of any adverse effects (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other trial compared anticholinergic withdrawal with anticholinergic continuation and found no evidence of a difference in the incidence of acceptability of treatment (measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95% CI 0.11 to 42.52; very low quality evidence).No trials reported on social confidence, social inclusion, social networks, or personalised quality of life - outcomes designated important to patients. No studies comparing either i. anticholinergics with placebo or no treatment, or ii. studies of anticholinergic withdrawal, were found that reported on the primary outcome 'no clinically important improvement in TD symptoms and adverse events'.

Authors' conclusions: Based on currently available evidence, no confident statement can be made about the effectiveness of anticholinergics to treat people with antipsychotic-induced tardive dyskinesia. The same applies for the withdrawal of such medications. Whether the withdrawal of anticholinergics may benefit people with antipsychotic-induced TD should be evaluated in a parallel-group, placebo-controlled randomised trial, with adequate sample size and at least 6 weeks of follow-up.

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Conflict of interest statement

Hanna Bergman worked for Enhance Reviews Ltd. during preparation of this review and was paid for her contribution to this review. Enhance Reviews Ltd. is a private company that performs systematic reviews of literature. HB works for Cochrane Response, an evidence consultancy linked to Cochrane that take commissions from healthcare guideline developers and policy makers.

Karla Soares‐Weiser is the Deputy Editor‐in‐Chief for Cochrane and Cochrane Innovations. When the NHIR HTA programme grant was awarded that included provision to update this review, Karla was the Managing Director of Enhance Reviews Ltd.

Figures

1
1
Message from one of the participants of the Public and patient involvement consultation of service user perspectives on tardive dyskinesia research.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Study flow diagram for 2015 and 2017 searches.
1.1
1.1. Analysis
Comparison 1 Anticholinergic medications versus other compounds, Outcome 1 TD symptoms: no clinically significant improvement.
1.2
1.2. Analysis
Comparison 1 Anticholinergic medications versus other compounds, Outcome 2 TD symptoms: not any improvement.
1.3
1.3. Analysis
Comparison 1 Anticholinergic medications versus other compounds, Outcome 3 Adverse effects.
1.4
1.4. Analysis
Comparison 1 Anticholinergic medications versus other compounds, Outcome 4 Leaving the study early.
2.1
2.1. Analysis
Comparison 2 Continuation versus withdrawal of anticholinergic medications, Outcome 1 Leaving the study early.
See this image and copyright information in PMC

Update of

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