title: A naturalistic comparison of the long-term metabolic adverse effects of clozapine versus other antipsychotics for patients with psychotic illnesses.
abstract: OBJECTIVE
  Clozapine, an evidence-based treatment of refractory schizophrenia, is associated with increased weight gain and metabolic dysregulation compared with most antipsychotics in short-term clinical trials. However, there are limited data describing comparative long-term metabolic risks. In this report, we examined whether short-term differences persist with long-term exposure to clozapine.
  
  
  METHODS
  The data of all patients in a university-based clinic with a psychotic illness or a mood disorder with psychotic features, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis, and treated with an antipsychotic in calendar year 2012 were examined. A total of 307 patients met the criteria; 96 patients were treated with clozapine and the remaining 211 patients were treated with 1 or more non-clozapine antipsychotics. Body mass index, type 2 diabetes, hypertension, dyslipidemia, and obesity were compared.
  
  
  RESULTS
  The mean duration of the clozapine treatment was 7.6 years (range, 2 months to 21 y). On all metabolic measures, there were no statistically significant differences between the clozapine and non-clozapine groups (mean body mass index, 31 vs 32; type 2 diabetes, 17% vs 18%; dyslipidemia, 35% vs 38%; hypertension, 32% vs 39%; and obesity, 48% vs 54%). Removing the olanzapine-treated patients (n = 51) from the non-clozapine group did not change the findings.
  
  
  CONCLUSIONS
  In this university-based clinic sample with a large number of clozapine-treated patients, we found no evidence of increased risk in any individual measure for those receiving clozapine. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time because multiple other variables likely also impact metabolic risk during the life span. Although speculative, the relative contribution of the increased short-term metabolic risk associated with clozapine may be diminished over time due to the accumulated impact of other variables that also impact metabolic risk across the life span.
authors.affiliation: From the *Department of Psychiatry, and †North Carolina Psychiatric Research Center, University of North Carolina at Chapel Hill, Chapel Hill; and ‡North Carolina Division of State Operated Healthcare Facilities, Raleigh, NC.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Kelly
authors.forename: Brian B
authors.initials: BB
authors.lastname: Sheitman
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hamer
authors.forename: David C
authors.initials: DC
authors.lastname: Rhyne
authors.forename: Robin M
authors.initials: RM
authors.lastname: Reed
authors.forename: Karen A
authors.initials: KA
authors.lastname: Graham
authors.forename: Shane W
authors.initials: SW
authors.lastname: Rau
authors.forename: John H
authors.initials: JH
authors.lastname: Gilmore
authors.forename: Diana O
authors.initials: DO
authors.lastname: Perkins
authors.forename: Susan Saik
authors.initials: SS
authors.lastname: Peebles
authors.forename: Carol J
authors.initials: CJ
authors.lastname: VanderZwaag
authors.forename: Lars Fredrik
authors.initials: LF
authors.lastname: Jarskog
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000378:metabolism; D057286:Electronic Health Records / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced* / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine