title: Mortality and Cumulative Exposure to Antipsychotics, Antidepressants, and Benzodiazepines in Patients With Schizophrenia: An Observational Follow-Up Study.
abstract: OBJECTIVE
  Although mortality related to psychotropic medications has received much attention in recent years, little is known about the relationship between risk of death and cumulative antipsychotic load, and even less about the relationship between mortality and cumulative exposure to antidepressants or benzodiazepines. The authors examined these relationships using nationwide databases.
  
  
  METHODS
  The authors used prospectively collected nationwide databases to identify all individuals 16-65 years of age with a schizophrenia diagnosis (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010.
  
  
  RESULTS
  Compared with no exposure, both moderate (adjusted hazard ratio=0.59, 95% CI=0.49-0.70) and high (adjusted hazard ratio=0.75, 95% CI=0.63-0.89) antipsychotic exposures were associated with substantially lower overall mortality. Moderate antidepressant exposure was associated with a lower mortality (adjusted hazard ratio=0.85, 95% CI=0.73-0.98), and high exposure, even lower (adjusted hazard ratio=0.71, 95% CI=0.59-0.86). Exposure to benzodiazepines showed a dose-response relationship with mortality (hazard ratios up to 1.74 [95% CI=1.50-2.03]).
  
  
  CONCLUSIONS
  Moderate and high-dose antipsychotic and antidepressant use were associated with 15%-40% lower overall mortality, whereas chronic high-dose use of benzodiazepines was associated with up to a 70% higher risk of death compared with no exposure. Since patients with anxiety and depressive symptoms may have a higher intrinsic risk of death, the finding for benzodiazepines may be attributable to some extent to residual confounding.
authors.affiliation: From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio; and the Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio; and the Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki.
authors.forename: Ellenor
authors.initials: E
authors.lastname: Mittendorfer-Rutz
authors.affiliation: From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio; and the Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki.
authors.forename: Minna
authors.initials: M
authors.lastname: Torniainen
authors.affiliation: From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio; and the Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki.
authors.forename: Kristina
authors.initials: K
authors.lastname: Alexanderson
authors.affiliation: From the Department of Clinical Neuroscience, Karolinska Institutet, Stockholm; the Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio; and the Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki.
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D016208:Databases, Factual; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012307:Risk Factors; D012559:Schizophrenia / Q000188:drug therapy* / Q000401:mortality*; D013548:Sweden; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D001569:Benzodiazepines