Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.

Purpose: Patients with drug-resistant epilepsy have a higher incidence of psychiatric problems and possibly greater intolerance to antiepileptic drugs (AEDs) than do other patients with epilepsy. Concern has been raised that gamma-aminobutyric acid (GABA)ergic drugs may be associated with treatment-emergent psychosis. Tiagabine (TGB; Gabitril), a new AED that blocks synaptic GABA uptake, was developed in trials of drug-resistant patients with epilepsy. We conducted ad hoc analyses of adverse events, drug intolerance, and treatment response to evaluate the association between TGB treatment and psychosis and whether psychiatric history might be predictive of tolerance or effectiveness of this GABAergic drug. Methods: Data were analyzed from two multicenter, randomized, double-blind, placebo-controlled trials of add-on TGB therapy (32 or 56 mg daily) in 554 adolescents and adults with complex partial seizures (CPSs). After an 8- or 12-week baseline phase, double-blind treatment consisted of a 4-week titration period (with TGB dose gradually increased to 32 or 56 mg daily) and an 8- or 12-week fixed-dose period. Adverse events commonly associated with psychosis were evaluated. Treatment intolerance and effectiveness (greater than or equal to50% reduction in CPS rate) were compared among patients with and without psychiatric histories. Results: Psychotic symptoms (hallucinations) were observed in three (0.8%) of 356 TGB-treated patients and none of 198 placebo-treated patients (p = 0.556, NS). Statistical analysis showed no interaction between psychiatric history and drug intolerance or treatment outcome. Conclusions: TGB administration appears to carry no significant increased risk of treatment-emergent psychosis. Psychiatric history was not predictive of the tolerance or effectiveness of the drug.