Gamma-aminobutyric acid agonists for neuroleptic-induced tardive dyskinesia

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 clinical effects of GABA agonist drugs (baclofen, gamma-vinyl-GABA, gamma-acetylenic-GABA, progabide, muscimol, sodium valproate and tetrahydroisoxazolopyridine (THIP) for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced tardive dyskinesia.

Search strategy: We updated the previous Cochrane review by searching the Cochrane Schizophrenia Group Register (June 2010).

Selection criteria: We included reports if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia or other chronic mental illness who had been randomly allocated to either non-benzodiazepine GABA agonist drugs with placebo or no intervention.

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 we calculated mean differences (MD).

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, 3 RCTs, 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, 4 RCTs, 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 left early 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, 5 RCTs, 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, 2 RCTs, RR 3.26 CI 0.4 to 30.2), and in sedation (n = 113, 3 RCTs, 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.