ObjectivesTimely recognition of medication misuse and dependence is crucial to avoid both adverse drug events and increasing health expenditure. Yet the detection of these disorders in older people remains challenging due to the paucity of evidence on characteristics of patients at risk. This study investigates sociodemographic, pharmacological and clinical characteristics and factors associated with prolonged medication use, misuse and dependence in hospitalised older patients, focusing on three commonly prescribed central nervous system depressants (CNSDs): opioid analgesics, benzodiazepines and z-hypnotics.DesignA prospective, cross-sectional study complying with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.SettingSomatic departments of the Akershus University Hospital, Norway.Participants246 patients aged 65–90 were included.Outcome measuresProlonged use was defined as using CNSDs for ≥4 weeks. Misuse and dependence were assessed with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for substance abuse and dependence. We used descriptive statistics to report patients’ characteristics and logistic regression to demonstrate factors associated with prolonged use, and misuse or dependence.ResultsForty per cent of participants reported using CNSDs for ≥4 weeks. The odds of prolonged use were higher for patients aged 75–84 (OR=2.32, 95% CI 1.16 to 4.65) and ≥85 (OR=3.33, 95% CI 1.25 to 8.87) vs <75 years, for pain intensity (OR=1.02, 95% CI 1.01 to 1.04), and polypharmacy versus no polypharmacy (OR=5.16, 95% CI 2.13 to 12.55). The odds were lower for patients who completed secondary education (OR=0.33, 95% CI 0.13 to 0.83) compared with those with only basic education. Factors associated with misuse or dependence were pain intensity (OR=1.02, 95% CI 1.01 to 1.04) and concurrent use of ≥2 CNSDs (OR=3.99, 95% CI 1.34 to 11.88).ConclusionCNSD overuse is prevalent among hospitalised older patients, despite clear guidelines and recommendations. Our findings underline a need for stronger focus on responsible prescribing, timely detection and prevention of this issue, with special attention towards older patients, those with enhanced pain, polypharmacy and/or concurrent use of several CNSDs.Trial registration numberNCT03162081.