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Meta-Analysis
. 2018 Mar 19;3(3):CD000207.
doi: 10.1002/14651858.CD000207.pub2.

Cholinergic medication for antipsychotic-induced tardive dyskinesia

Irina Tammenmaa-Aho  1 , Rosie Asher, Karla Soares-Weiser, Hanna Bergman
Affiliations
Meta-Analysis

Cholinergic medication for antipsychotic-induced tardive dyskinesia

Irina Tammenmaa-Aho et al. Cochrane Database Syst Rev. .

Abstract

Background: Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component of central cholinergic deficiency. Cholinergic drugs have been used to treat TD.

Objectives: To determine the effects of cholinergic drugs (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86, tacrine, metoxytacrine, galantamine, ipidacrine, donepezil, rivastigmine, eptastigmine, metrifonate, xanomeline, cevimeline) for treating antipsychotic-induced TD in people with schizophrenia or other chronic mental illness.

Search methods: An electronic search of the Cochrane Schizophrenia Group's Study-Based Register of Trials (16 July 2015 and April 2017) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of trials, conference proceedings and dissertations. References of all identified studies were searched for further trial citations.

Selection criteria: We included reports identified by the search if they were of controlled trials involving people with antipsychotic-induced TD and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two review authors independently assessed the methodological quality of the trials.

Data collection and analysis: Two review authors extracted data and, where possible, estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We analysed data on an intention-to-treat basis, with the assumption that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE.

Main results: We included 14 studies investigating the use of cholinergic drugs compared with placebo published between 1976 and 2014. All studies involved small numbers of participants (five to 60 people). Three studies that investigated the new cholinergic Alzheimer drugs for the treatment of TD are new to this update. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, we are unsure if data are incomplete, and data were often poorly or selectively reported.We are uncertain about the effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms when compared with placebo; the quality of evidence was very low (RR 0.89, 95% CI 0.65 to 1.23; 27 people, 4 RCTs). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people). Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs). No study reported on social confidence, social inclusion, social networks, or personalised quality of life.

Authors' conclusions: TD remains a major public health problem. The clinical effects of both older cholinergic drugs and new cholinergic agents, now used for treating Alzheimer's disease, are unclear, as too few, too small studies leave many questions unanswered. Cholinergic drugs should remain of interest to researchers and currently have little place in routine clinical work. However, with the advent of new cholinergic agents now used for treating Alzheimer's disease, scope exists for more informative trials. If these new cholinergic agents are to be investigated for treating people with TD, their effects should be demonstrated in large well-designed, conducted and reported randomised trials.

PubMed Disclaimer

Conflict of interest statement

Irina Tammenmaa‐Aho ‐ None.

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

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 that takes commissions from healthcare guideline developers and policy makers.

Rosie Asher ‐ worked for Enhance Reviews Ltd. during preparation of this review and was paid for her contribution to this review.

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
Study flow diagram for 2015 and 2017 searches.
3
3
'Risk of bias, summary: review authors' judgements about each risk of bias item for each included study.
4
4
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 1 Tardive dyskinesia: 1. No clinically important improvement (50% or more change on any validated TD scale).
1.2
1.2. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 2 Tardive dyskinesia: 2a. Not any improvement (as assessed by rater).
1.3
1.3. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 3 Tardive dyskinesia: 2b. Not any improvement (as assessed by self report).
1.4
1.4. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 4 Tardive dyskinesia: 3a. Average endpoint score on AIMS (low score = better).
1.6
1.6. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 6 Tardive dyskinesia: 4a. Deterioration (as assessed by rater).
1.7
1.7. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 7 Tardive dyskinesia: 4b. Deterioration (as assessed by self report).
1.8
1.8. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 8 Global outcome: Death for any reason.
1.9
1.9. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 9 Global outcome: Intervention not useful as assessed by Global Usefulness Rating (GUR).
1.10
1.10. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 10 Global state: Average endpoint score on CGI (low score = better).
1.11
1.11. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 11 Mental state: Deterioration.
1.12
1.12. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 12 Adverse effects: Any.
1.13
1.13. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 13 Adverse effects: Various specific.
1.14
1.14. Analysis
Comparison 1 CHOLINERGIC DRUGS versus PLACEBO, Outcome 14 Leaving the study early.
2.1
2.1. Analysis
Comparison 2 CHOLINERGIC DRUGS versus OTHER CHOLINERGIC DRUGS, Outcome 1 Tardive dyskinesia: 2a. Not any improvement (as assessed by rater) ‐ less than 6 weeks.
2.2
2.2. Analysis
Comparison 2 CHOLINERGIC DRUGS versus OTHER CHOLINERGIC DRUGS, Outcome 2 Global outcome: Death for any reason ‐ less than 6 weeks.
2.3
2.3. Analysis
Comparison 2 CHOLINERGIC DRUGS versus OTHER CHOLINERGIC DRUGS, Outcome 3 Leaving the study early ‐ less than 6 weeks.
See this image and copyright information in PMC

Update of

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