This study found a significant increase in all-cause mortality associated with benzodiazepine use with or without opioid use in comparison with SSRI use.

Benzodiazepine and opioid co-treatment, in particular, was associated with a 2-fold increase in all-cause mortality even after taking into account medical comorbidities and polypharmacy burden.

Of 5,212 participants aged 20 years or older (1,993 men [38.2%]; mean [SD] age, 54.8 [16.9] years) followed up for a median of 6.7 years (range, 0.2-16.8 years), 101 deaths (33.0 per 1000 person-years) occurred among those receiving cotreatment, 236 deaths (26.5 per 1,000 person-years) occurred among those receiving only benzodiazepines, and 227 deaths (20.2 per 1000 person-years) occurred among SSRI recipients taking neither opioids nor benzodiazepines.

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