Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia.

Abstract

Chronic antipsychotic drug treatment may cause tardive dyskinesia (TD), a long-term movement disorder. The gamma-aminobutyric acid (GABA) agonist drugs have been trialed as a treatment for TD, but these drugs have intense sedative properties and may exacerbate psychotic symptoms. To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) for people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses. Electronic searches of Biological Abstracts (1982-2000), The Cochrane Library (Issue 4, 2000), Cochrane Schizophrenia Group's Register of Trials (2000), EMBASE (1980-2000), LILACS (1982-2000), MEDLINE (1966-2000), PsycLIT (1974-2000), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. First authors of each included trial were contacted. The inclusion criteria for all relevant randomised studies were that they should focus on people with schizophrenia or other chronic mental illnesses, with neuroleptic-induced TD and compare the use of non-benzodiazepine GABA agonist drugs to placebo or no intervention. The reviewers extracted the data independently and the relative risk (RR) and its 95% confidence interval (CI) or the weighted mean difference with 95% CI were estimated. The reviewers assumed that people who dropped out had no improvement. Eight small, short, poorly reported studies were included. For the outcome of 'no clinically important improvement in tardive dyskinesia' GABA agonist drugs were not clearly better than placebo (n=108, RR 0.83 CI 0.6 to 1.1). Deterioration in mental state was more likely to occur for people receiving GABA medication (n=95, RR 2.55 CI 1.17 to 5.59), but this effect was influenced by the decision to assign a negative outcome to those who dropped out before the end of the study. A greater proportion of people allocated GABA medication may fail to complete the trial compared with those allocated placebo (20% versus 9%) but, this difference was not statistically significant (n=136, RR 1.99 CI 0.84 to 4.68). There is a suggestion of an increase in ataxia for both baclofen and sodium valproate (n=95, RR 3.26 CI 0.4 to 30), and in sedation (n=113, RR 2.12 CI 0.8 to 5.4) compared with placebo. Withdrawal of THIP may cause seizures. Currently, evidence of effect of baclofen, progabide, sodium valproate, or THIP for people with neuroleptic-induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with the use of these drugs.