Association of co-prescribing of opioid and benzodiazepine substitutes with incident falls and fractures among older adults: a cohort study.

Objective: Examine the association between the co-prescribing of opioids, benzodiazepines, gabapentinoids (pregabalin and gabapentin) and selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitors (SSRI/SNRIs) in different combinations and the risk of falls and fractures.

Design: Retrospective cohort study from 2015 to 2018. Setting: Medicare enrolment and claims data. Participants: Medicare beneficiaries with both chronic pain and anxiety disorders in 2016 with continuous enrolments in Parts A and B from 2015 to 2016 who were prescribed any combination of opioid, benzodiazepine, gabapentinoid and SSRI/SNRI in 2017 for ≥7 days, as documented in their Medicare Part D coverage. Interventions: Any combination of use of seven drug regimens (benzodiazepine +opioid; benzodiazepine +gabapentinoid; benzodiazepine +SSRI/SNRI; opioid +gabapentinoid; opioid +SSRI/SNRI; gabapentinoid +SSRI/SNRI; ≥3 drug classes). Main outcomes: First event of fall and the first event of fracture after the index date, which was the first day of combination drug use that lasted ≥7 days in 2017.

Results: A total of 47 964 patients (mean [SD] age, 75.9 [7.1]; 78.0% woman) with diagnoses of both chronic pain and anxiety were studied. The median (Q1-Q3) duration of drug combination use was 26 (14-30) days. After adjusting for demographic characteristics, chronic conditions and history of hospitalisation and fall or fracture, the co-prescribing of ≥3 drugs (adjusted HR [aHR], 1.38; 95% CI 1.14 to 1.67) and opioid plus gabapentinoid (aHR, 1.18; 95% CI 1.02 to 1.37) were associated with a high fall risk, compared with benzodiazepineplus opioid co-prescribing, findings consistent with the secondary analysis using inverse probability of treatment weighting with propensity scores. The co-prescribing of benzodiazepine plus gabapentinoid (aHR, 0.76; 95% CI 0.59 to 0.98) was associated with lower fracture risk compared with the co-prescribing of benzodiazepine plus opioid, though this finding was not robust.

Conclusions: Our findings add to comparative toxicity research on different combinations of gabapentinoids and serotonergic agents commonly prescribed with or as substitutes for opioids and benzodiazepines in patients with co-occurring chronic pain and anxiety.