title: Comparative risk of seizure with use of first- and second-generation antipsychotics in patients with schizophrenia and mood disorders.
abstract: OBJECTIVE
  To compare the risk of antipsychotic-related seizure (ARS) by identifying seizures first diagnosed within 12 months after starting new antipsychotics, using a 12-year total population health claims database from Taiwan.
  
  
  METHODS
  Seizure events were identified through emergency department visits or hospitalization with a diagnosis of convulsion (ICD-9-CM: 780.3) or epilepsy (ICD-9-CM: 345). Subjects had an ICD-9-CM diagnosis of schizophrenia, bipolar disorders, or major depressive disorders. Incidence rates of ARS were calculated by person-years of exposure. The ARS risk, adjusted for patient characteristics and medical conditions, of individual antipsychotics versus risperidone was examined by high-dimensional propensity score stratification analyses, followed by sensitivity analyses.
  
  
  RESULTS
  The overall 1-year incidence rate of ARS was 9.6 (95% CI, 8.8-10.4) per 1,000 person-years (550 ARS events among 288,397 new antipsychotic users). First-generation antipsychotics were marginally associated with a higher ARS risk than second-generation antipsychotics (adjusted hazard ratio [aHR] = 1.34; 95% CI, 0.99-1.81; P = .061). Most antipsychotics, first- or second-generation, had comparable ARS risks versus risperidone. Notably, clozapine (aHR = 3.06; 95% CI, 1.40-6.71), thioridazine (aHR = 2.90; 95% CI, 1.65-5.10), chlorprothixene (aHR = 2.60; 95% CI, 1.04-6.49), and haloperidol (aHR = 2.34; 95% CI, 1.48-3.71) had higher ARS risks than risperidone, whereas aripiprazole (aHR = 0.41; 95% CI, 0.17-1.00; P = .050) had a marginally lower ARS risk. Sensitivity analyses largely confirmed such findings.
  
  
  CONCLUSIONS
  Higher vigilance for ARS is warranted during use of clozapine, chlorprothixene, thioridazine, and haloperidol. The possible lower ARS risk associated with aripiprazole can be clinically significant but needs to be confirmed by larger-scale systematic studies. The comparative ARS risks of antipsychotics supplement empirical knowledge for making judicious choices in prescribing antipsychotics.
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Psychiatry, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
authors.forename: Chi-Shin
authors.initials: CS
authors.lastname: Wu
authors.forename: Sheng-Chang
authors.initials: SC
authors.lastname: Wang
authors.forename: I-Jin
authors.initials: IJ
authors.lastname: Yeh
authors.forename: Shi-Kai
authors.initials: SK
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000453:epidemiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology; D012640:Seizures / Q000139:chemically induced* / Q000453:epidemiology*; D013624:Taiwan; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents