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. Gamma‐aminobutyric acid (GABA) agonist drugs, which have intense sedative properties and may exacerbate psychotic symptoms, have been used to treat TD.
Objectives
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 antipsychotic‐induced tardive dyskinesia (TD) and schizophrenia or other chronic mental illnesses.
Search methods
We updated the previous Cochrane review by searching the Cochrane Schizophrenia Group Register (September 2003). We searched references for further trial citations and, where possible, contacted authors.
Selection criteria
Randomised controlled trials comparing use of non‐benzodiazepine GABA agonist drugs with placebo or no intervention, involving people with schizophrenia or other chronic mental illnesses with signs of antipsychotic‐induced TD.
Data collection and analysis
Working independently, we selected and critically appraised studies, extracted data and analysed on an intention‐to‐treat basis. Where possible and appropriate we calculated risk ratios (RR) and their 95% confidence intervals (CI) with the number needed to treat (NNT). For continuous data Weighted Mean Differences (WMD) were calculated.
Main results
We identified eight small poorly reported studies for inclusion. 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 in people receiving GABA medication (n = 95, RR 2.47 CI 1.1 to 5.4), 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 0.8 to 4.7). There is a suggestion of an increase in ataxia (loss of power of muscular coordination) for both baclofen and sodium valproate (n = 95, RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, RR 2.12 CI 0.8 to 5.4) compared with placebo, but this was not significant. Withdrawal of tetrahydroisoxazolopyridine (THIP) may cause seizures.
Authors' conclusions
Evidence of the effects of baclofen, progabide, sodium valproate, or THIP for people with antipsychotic‐induced TD is inconclusive and unconvincing. Any possible benefits are likely to be outweighed by the adverse effects associated with their use.
PICOs
Plain language summary
Gamma‐aminobutyric acid agonists for neuroleptic‐induced tardive dyskinesia
Taking antipsychotic drugs for long periods of time can cause repetitive movements that often occur in the face and mouth. These are disfiguring and do not necessarily cease once medication is reduced or changed. In this review we consider one group of drugs that has been evaluated for treating these movement disorders: the so‐called 'GABA agonist' group of drugs. We found no convincing evidence regarding its efficacy in every day practice and there are some data to suggest that adverse effects resulting from its use may in fact prohibit clinical use.
