Benzodiazepine use and risk of mortality among patients with schizophrenia: a retrospective longitudinal study

J Clin Psychiatry. 2016 May;77(5):661-7. doi: 10.4088/JCP.15m10271.


Objective: This study examined the association between benzodiazepine use alone or in combination with antipsychotics and risk of mortality in patients with schizophrenia.

Methods: A retrospective longitudinal analysis was performed using Medicaid claims data merged with death certificate data for 18,953 patients (aged 18-58 years) with ICD-9-diagnosed schizophrenia followed from July 1, 2006, to December 31, 2013. Cox proportional hazard analyses were used to estimate the risk of all-cause mortality associated with benzodiazepine use; adjustment was made for a wide array of fixed and time-varying confounders, including demographics, psychiatric and medical comorbidities, and other psychotropic medications.

Results: Of the 18,953 patients diagnosed with schizophrenia, 13,741 (72.5%) were not prescribed a benzodiazepine, 3,476 (18.3%) were prescribed benzodiazepines in the absence of antipsychotic medication, and 1,736 (9.2%) were prescribed benzodiazepines in combination with antipsychotics. Controlling for a wide array of demographic and clinical variables, the hazard of mortality was 208% higher for patients prescribed benzodiazepines without an antipsychotic (HR = 3.08; 95% CI, 2.63-3.61; P < .001) and 48% higher for patients prescribed benzodiazepines in combination with antipsychotics (HR = 1.48; 95% CI, 1.15-1.91; P = .002). Benzodiazepine-prescribed patients were at greater risk of death by suicide and accidental poisoning as well as from natural causes.

Conclusions: Benzodiazepine use is associated with increased mortality risk in patients with schizophrenia after adjusting for a wide range of potential confounders. Given unproven efficacy, physicians should exercise caution in prescribing benzodiazepines to schizophrenic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / adverse effects*
  • Benzodiazepines / therapeutic use*
  • Cause of Death
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Schizophrenia / drug therapy*
  • Schizophrenia / mortality*
  • Young Adult


  • Antipsychotic Agents
  • Benzodiazepines