Risk of death is increased in patients taking benzodiazepines, antidepressants, and antipsychotics regardless of whether or not they have dementia, according to a report by Danish researchers published in European Neuropsychopharmacology. The findings — from one of the largest ever studies of use of the drugs in individuals with dementia and matched controls — suggest a need for caution when prescribing these types of medication to the elderly. The population-based register study included 26,821 adults with a diagnosis of dementia between 1997 and 2009 and 44,286 controls with a minimum follow-up of 4 years, who were matched for age, gender, marital status, and community location [Eur Neuropsychopharmacol doi.org/10.1016/j.euroneuro.2015.08.014]. Data on the participants were taken from the Danish National Patient Registry; data on use of psychotropic medications were taken from the Danish Medicinal Product Statistics. Complete data were available for more than 99% of the patients and controls, who were traced retrospectively and prospectively for up to 12 years in the databases. The medications included in the analysis were selective serotonin reuptake inhibitors, serotonin-noradrenaline re-uptake inhibitors, tricyclic antidepressants, benzodiazepines, benzodiazepine-like drugs, first-generation antipsychotics, and second-generation anti-psychotics. Participants were considered to have taken antipsychotic medication if they received at least three prescriptions with a coverage rate of a least 60% in the 12 months before the index date. Patients in the control group had received no prescriptions for psychotropic drugs in the 12 months pre- or post-incident. Looking at survival in the year after a dementia diagnosis, Poul Jennum, MD, DSc, and colleagues found a statistically significant association between use of psychotropic medication and death, which was significantly more pronounced in controls than in patients with dementia. Use of the drugs by individuals without dementia, the authors said, might indicate they had mental health disorders with an intrinsically higher risk of death than the non-medicated patients in the control group. “We found that use of psychotropic drugs was associated with increased all-cause mortality in both patients with dementia and control subjects,” Dr. Jennum and colleagues said. “Thus, the frequently reported increased mortality with antipsychotic drugs in dementia was not restricted to subjects with impaired cognition and was not restricted to only one class of psychotropic drugs.” Examining the reasons for the increased risk of death associated with psychotropic drugs, the authors postulated that a number of factors may be at play. The medications may affect arousals from sleep as well as metabolic, respiratory, autonomic, and cardiac functions, as previously suggested by reports about benzodiazepine's impact on respiration and clonazepam's potential to induce sleep apnea. Limitations of the study cited by the researchers include lack of information about the manner and cause of death of the participants and the possibility that many of the patients in the control group may have been suffering from mental illness; lack of information about confounder variables, making it impossible to relate the findings to disease severity; and the likelihood that some patients in the control group may have had as-yet-undiagnosed dementia. “There are several questions that should be addressed in future studies, including duration and dose of treatment, subgroup analysis on specific co-morbidities, and manner and cause of death,” Dr. Jennum and colleagues wrote. The study authors reported no conflicts of interest. Judith M. Orvos, ELS, is a freelance medical writer and president of Orvos Communications in Washington, DC.