Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia

Abstract

Background: 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 can possibly exacerbate psychotic symptoms.

Objectives: To determine the effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP)) in people with neuroleptic-induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses.

Search strategy: Electronic searches of Biological Abstracts (1982-1998), The Cochrane Library CENTRAL (1998), Cochrane Schizophrenia Group's Register of Trials (1998), EMBASE (1980-1998), LILACS (1982-1996), MEDLINE (1966-1998), PsycLIT (1974-1998), and SCISEARCH were undertaken. References of all identified studies were searched for further trial citations. First authors of each included trial were contacted.

Selection criteria: 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 GABA agonist drugs to placebo or no intervention.

Data collection and analysis: The reviewers extracted the data independently and the odds ratio (OR) 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.

Main results: Eight studies were able to be included. Results were equivocal, showing only a tendency for clinical improvement for those using GABA agonist drugs but, when analysis of any improvement (rather than clinical improvement) was performed, a significant reduction was noted in the GABA group (OR 0.36 CI 0.15-0.85). This suggests that for every 10 people treated with GABA drugs one person would benefit with a reduction in TD symptoms. People using the interventions had more confusion (OR 7.4 CI 1.3-40.9) and sedation (OR 3.0 CI 1.2-7.6). The numbers of people needed to treat to cause one extra person to experience these side effects were three and six, respectively. Tendency for more deterioration of the TD symptoms (OR 1.72 CI 0. 54-5.5), deterioration of the mental state (OR 3.07 CI 0.78-12.05), and to drop out before the end of the trial (OR 2.05 CI 0.8-5.21) were also observed in those using GABA agonists.

Reviewer's conclusions: No clear statement about the efficacy of GABA agonist drugs could be provided. From the combined data, GABA agonist drugs tend to be associated with some degree of improvement in TD symptoms, but also with side effects such as confusion and sedation and a deterioration of the person's mental state.