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Cholinergic medication for neuroleptic-induced tardive dyskinesia.
Cochrane Database Syst Rev 2002; (3):CD000207CD

Abstract

BACKGROUND

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

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 neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illness.

SEARCH STRATEGY

An electronic search of the Cochrane Schizophrenia Group's register (October 2001) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of conference proceedings and dissertations. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted.

SELECTION CRITERIA

Reports identified by the search were included if they were of controlled trials dealing with people with neuroleptic-induced tardive dyskinesia and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two reviewers independently assessed methodological quality of trials.

DATA COLLECTION AND ANALYSIS

Two researchers extracted data and, where possible, estimated relative risks (RR) or weighted mean differences (WMD), with 95% confidence intervals (CI). Data were analysed on an intention-to-treat basis, with the assumption that people who dropped out had no improvement.

MAIN RESULTS

We included eleven studies investigating the use of older cholinergic drugs compared with placebo. Most studies involved small numbers of participants (5-20 people). We found no completed trials of the new cholinergic Alzheimer drugs for the treatment of tardive dyskinesia. Cholinergic drugs did not result in any substantial improvement in tardive dyskinesia symptoms when compared with placebo (8 RCTs, 170 people, RR no important improvement 0.84 CI 0.68 to 1.04). Neither did tardive dyskinesia symptoms increase (7 RCTs, 137 people, RR deterioration in tardive dyskinesia 1.17 CI 0.55 to 2.50). Pooled results for endpoint AIMS scores were equivocal (4 RCTs, 86 people, WMD -0.19 CI -0.53 to 0.14). Deanol may cause gastric adverse effects (5 RCTs, 61 people, RR 9.00 CI 0.55-148) and other adverse effects such as sedation and peripheral cholinergic effects (6 RCTs, 94 people, RR 6.83 CI 0.99-47). One study reported on global outcome. Meclofenoxate was neither clearly helpful nor harmful when compared with placebo (1 RCT, 60 people, RR not of global benefit 0.89 CI 0.59 to 1.32). We found no difference between people allocated cholinergics and those given placebo for the outcome of leaving the study before completion (10 RCTs, 240 people, RR 0.52 CI 0.21 to 1.33).

REVIEWER'S CONCLUSIONS

Tardive dyskinesia remains a major public health problem. The clinical effects of older cholinergic drugs 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 tardive dyskinesia, their effects should be demonstrated in well-designed, conducted and reported randomised trials.

Authors+Show Affiliations

Department of Psychiatry, University of Helsinki, Lapinlahti Hospital, P.O.Box 320, FIN-00029 Helsinki University Central Hospital, Finland. irina.tammenmaa@helsinki.fiNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review
Systematic Review

Language

eng

PubMed ID

12137608

Citation

Tammenmaa, I A., et al. "Cholinergic Medication for Neuroleptic-induced Tardive Dyskinesia." The Cochrane Database of Systematic Reviews, 2002, p. CD000207.
Tammenmaa IA, McGrath JJ, Sailas E, et al. Cholinergic medication for neuroleptic-induced tardive dyskinesia. Cochrane Database Syst Rev. 2002.
Tammenmaa, I. A., McGrath, J. J., Sailas, E., & Soares-Weiser, K. (2002). Cholinergic medication for neuroleptic-induced tardive dyskinesia. The Cochrane Database of Systematic Reviews, (3), p. CD000207.
Tammenmaa IA, et al. Cholinergic Medication for Neuroleptic-induced Tardive Dyskinesia. Cochrane Database Syst Rev. 2002;(3)CD000207. PubMed PMID: 12137608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinergic medication for neuroleptic-induced tardive dyskinesia. AU - Tammenmaa,I A, AU - McGrath,J J, AU - Sailas,E, AU - Soares-Weiser,K, PY - 2002/7/26/pubmed PY - 2002/9/25/medline PY - 2002/7/26/entrez SP - CD000207 EP - CD000207 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 3 N2 - BACKGROUND: Tardive dyskinesia remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that tardive dyskinesia could have a component of central cholinergic deficiency. Cholinergic drugs have been used to treat tardive dyskinesia. 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 neuroleptic-induced tardive dyskinesia in people with schizophrenia or other chronic mental illness. SEARCH STRATEGY: An electronic search of the Cochrane Schizophrenia Group's register (October 2001) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of conference proceedings and dissertations. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted. SELECTION CRITERIA: Reports identified by the search were included if they were of controlled trials dealing with people with neuroleptic-induced tardive dyskinesia and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two reviewers independently assessed methodological quality of trials. DATA COLLECTION AND ANALYSIS: Two researchers extracted data and, where possible, estimated relative risks (RR) or weighted mean differences (WMD), with 95% confidence intervals (CI). Data were analysed on an intention-to-treat basis, with the assumption that people who dropped out had no improvement. MAIN RESULTS: We included eleven studies investigating the use of older cholinergic drugs compared with placebo. Most studies involved small numbers of participants (5-20 people). We found no completed trials of the new cholinergic Alzheimer drugs for the treatment of tardive dyskinesia. Cholinergic drugs did not result in any substantial improvement in tardive dyskinesia symptoms when compared with placebo (8 RCTs, 170 people, RR no important improvement 0.84 CI 0.68 to 1.04). Neither did tardive dyskinesia symptoms increase (7 RCTs, 137 people, RR deterioration in tardive dyskinesia 1.17 CI 0.55 to 2.50). Pooled results for endpoint AIMS scores were equivocal (4 RCTs, 86 people, WMD -0.19 CI -0.53 to 0.14). Deanol may cause gastric adverse effects (5 RCTs, 61 people, RR 9.00 CI 0.55-148) and other adverse effects such as sedation and peripheral cholinergic effects (6 RCTs, 94 people, RR 6.83 CI 0.99-47). One study reported on global outcome. Meclofenoxate was neither clearly helpful nor harmful when compared with placebo (1 RCT, 60 people, RR not of global benefit 0.89 CI 0.59 to 1.32). We found no difference between people allocated cholinergics and those given placebo for the outcome of leaving the study before completion (10 RCTs, 240 people, RR 0.52 CI 0.21 to 1.33). REVIEWER'S CONCLUSIONS: Tardive dyskinesia remains a major public health problem. The clinical effects of older cholinergic drugs 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 tardive dyskinesia, their effects should be demonstrated in well-designed, conducted and reported randomised trials. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/12137608/Cholinergic_medication_for_neuroleptic_induced_tardive_dyskinesia_ L2 - https://doi.org/10.1002/14651858.CD000207 DB - PRIME DP - Unbound Medicine ER -