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Does the use of benzodiazepine influence the effectiveness of lifestyle intervention? Secondary analysis from the Sarcopenia and Physical fRailty iN older people strategies (SPRINTT) trial

Age Ageing. 2026 Aug 3;55(8):afag257. doi: 10.1093/ageing/afag257.

ABSTRACT

PURPOSE: Benzodiazepine use is prevalent among older adults despite its recognised negative effects, including increased risk of falls, fractures and decline in functional status. Lifestyle interventions can preserve physical function and reduce the risk of disability. This study investigates whether benzodiazepine use reduces the effectiveness of lifestyle-based interventions on mobility disability.

METHODS: We performed a secondary analysis of the ‘Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies’ trial. The lifestyle intervention consisted of physical exercise and nutritional counselling. Benzodiazepine use was assessed based on baseline or longitudinal exposure (defined as use at baseline plus use at two or more additional time points). Cox regression models were used to ascertain the association between benzodiazepine use and mobility disability incidence. A separate analysis was conducted among participants with a Short Physical Performance Battery (SPPB) score 3 to 7.

RESULTS: Among the 1506 participants included (mean age 78.9 years; 71.5% female; 753 intervention vs. 753 control), 211 (14.0%) reported benzodiazepine use at baseline. Overall, 55.0% of baseline benzodiazepine users and 43.6% of non-users developed mobility disability during the follow-up (P = .003). When baseline benzodiazepine use was considered, no significant effect associated with multicomponent intervention (MCI) was shown among non-users (Hazard Ratio (HR) = 0.86; 95% Confidence Interval (CI) 0.72-1.03) and users (HR = 1.04; CI 0.67-1.62). In the subgroup of participants with SPPB scores 3 to 7, a significant effect of the MCI was observed only among non-users (HR = 0.80, 95% CI 0.66-0.97), while no ‘association’ was detected among users (HR = 1.06; 95% CI 0.65-1.71, P for interaction = .035). When longitudinal benzodiazepine exposure was considered, similar results were observed. In particular, in the SPPB score 3 to 7 subgroup, the beneficial effect of the MCI was observed only among non-users (HR = 0.79; 95% CI 0.64-0.96), while no ‘association’ was detected among users (HR = 1.13; 95% CI 0.60-2.13, P for interaction = .035).

CONCLUSION: In frail older adults, benzodiazepine use significantly blunts the effectiveness of lifestyle interventions for preventing mobility disability. These findings support a prudent approach to benzodiazepine use in frail older patients.

PMID:42685256 | DOI:10.1093/ageing/afag257