title: Occurrence of psychosis in patients with epilepsy randomized to tiagabine or placebo treatment.
abstract: OBJECTIVE
  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 (> or =50% 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.
authors.affiliation: Department of Neuroscience, University of Florida and Gainesville VA Medical Center, Room L1-100, 100 Newell Drive, Gainesville, FL 32610, USA. sackellares@epilepsy.health.ufl.edu
authors.forename: J Chris
authors.initials: JC
authors.lastname: Sackellares
authors.forename: Gregory
authors.initials: G
authors.lastname: Krauss
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Sommerville
authors.forename: Roger
authors.initials: R
authors.lastname: Deaton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D018755:GABA Agonists / Q000009:adverse effects*; D006212:Hallucinations / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009557:Nipecotic Acids / Q000009:adverse effects*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D000078308:Tiagabine
chemical_list: D018755:GABA Agonists; D009557:Nipecotic Acids; D010919:Placebos; D000078308:Tiagabine