To increase overlap of measured characteristics between benzodiazepine-opioid users and nonusers, we used an active comparator group of participants who were not taking benzodiazepines or opioids and had an active prescription for SSRIs. This is a validated approach taken to address unobserved confounding factors given SSRIs’ overlapping indications with benzodiazepines without any known association with all-cause mortality in adults.20,31 We selected SSRIs as our active comparator rather than non-SSRI antidepressants owing to substantial heterogeneity in non-SSRIs’ indications for use in comparison with benzodiazepines (ie, tricyclic antidepressants for headache and serotonin norepinephrine reuptake inhibitors for neuropathic pain)20 as well as increased morbidity and mortality associated with monoamine oxidase inhibitors and tricyclic antidepressants.32
