High Benzodiazepine Use for Schizophrenia Increases Risk of Death

Chronic, high-dose use of benzodiazepines among patients with schizophrenia appears to be associated with a markedly higher overall mortality rate than is seen in patients with schizophrenia who have not been exposed to benzodiazepines, according to a report in AJP in Advance.

The report also found a lower overall mortality rate among patients with schizophrenia who received antipsychotics and/or antidepressants.

“The results indicate that any amount of antipsychotic and antidepressant usage is associated with overall mortality rates 15% to 40% lower compared with no use of these medications,” the researchers wrote. “In contrast, benzodiazepine exposure revealed a clear dose-response curve for mortality, where high exposure was associated with a 70% higher risk of death compared with no use.”

The authors prospectively compared all-cause and cause-specific mortality in individuals aged 16 to 65 who had been diagnosed with schizophrenia (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. The cohort participants were identified from two nationwide Swedish health care registers.

The researchers found that antipsychotic exposures at any dose were associated with substantially lower overall mortality. Moreover, moderate antidepressant exposure was associated with a lower mortality, and high exposure to antidepressants was associated with even lower mortality. But exposure to benzodiazepines showed a dose-response relationship with mortality.

“The association between benzodiazepine exposure and mortality may be explained by several mechanisms,” the authors noted. “Although long-term benzodiazepine use may be a marker for more severe illness and coexisting substance abuse, it is also plausible to assume that prescribing of high doses for long periods may lead to tolerance and dose escalation. This could result in fatal interactions with concurrent use of alcohol and illicit drugs, and worsening of polysubstance dependence may result in a less healthy lifestyle in general. In addition, high-dose benzodiazepine use may also contribute to daytime sedation and proneness to accidents.”

For related information, see the Psychiatric News article “Benzodiazepines: Experts Urge Balance.”

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