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Benzodiazepine Use and Risk of Mortality Among Patients With Schizophrenia: A Retrospective Longitudinal Study

J Clin Psychiatry 2016;77(5):661–667

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.