Cholinergic medication for neuroleptic-induced tardive dyskinesia

Since the 1950's neuroleptic medication has been extensively used to treat people with chronic mental illnesses, such as schizophrenia. These may cause tardive dyskinesia (TD), abnormal, repetitive and involuntary movements, in up to 20% of those using the medication for longer than three months. One theory of causation supports the use of cholinergic drugs for the management of TD.

To determine whether the use of cholinergic agents (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86) were associated with clinical improvement in neuroleptic-induced TD in people with schizophrenia or other chronic mental illnesses.

Electronic searches of Biological Abstracts (1982-1995), Cochrane Schizophrenia Group's Register of trials (1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995), PsycLIT (1974-1995), and SCISEARCH (1995) were undertaken. References of all identified studies were searched for further trial citations. Principal authors of trials were contacted.

Reports identified in the search were included if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illnesses who had been randomly allocated to either a cholinergic agent or to a placebo (or no intervention).

Seven different studies (8 references) were included in this review, and another ten trials are currently awaiting further data from authors. Data were independently extracted from these trials by each reviewer and odds ratios (OR) or average differences, with the 95% confidence intervals (95% CI) were estimated. The reviewers assumed that people who dropped out had no improvement.

The studies failed to detect any significant advantage of deanol or lecithin when compared to placebo. Data from two deanol trials demonstrated an excess of side effects in the active treatment group. People on cholinergic compounds report a range of gastrointestinal adverse effects (anorexia, nausea, vomiting, diarrhea, abdominal pain), sedation, and undesirable body odour. One person died of acute aspiration in a deanol versus placebo cross-over study.

This review provides no strong evidence for the use of cholinergic agents in the treatment of neuroleptic-induced tardive dyskinesia. While people receiving cholinergic treatment had a marginal benefit compared to placebo, because of the small sample size, the cumulative data must be interpreted as inconclusive. Clinicians and trialists considering using cholinergic agents to treat TD should balance the lack of evidence for the efficacy against the excess of side effects associated with these compounds.