Of the 10 900 patients included in the study cohort, 1942 initiated an atypical antipsychotic, 1902 a conventional antipsychotic, 2169 an anti-depressant and 4887 a benzodiazepine. Most patients initiated treatment shortly after admission (median 1 day, interquartile range 0–13 days).
Overall, users of atypical antipsychotics had more diagnosed psychiatric comorbidities, used more medications indicated for dementia and psychotropic medications, and had more visits to psychiatrists (). Compared with users of atypical antipsychotics, users of conventional antipsychotics had fewer comorbidities and required less intensive care. Users of antidepressants were sicker than users of atypical antipsychotics, with considerably more pre-existing diseases of the circulatory system, diabetes, chronic lung disease and prior fractures, and with worse general indicators of comorbidity. Users of benzodiazepines had more pre-existing cardiovascular disease, diabetes, chronic lung disease and fractures than users of atypical antipsychotics, but general indicators of comorbidity indicated they were in slightly better health otherwise.
Characteristics of the study cohort, stratified by class of medication
Rates of noncancer-related mortality, femur fracture, heart failure and stroke were lower among patients who initiated atypical antipsychotics than among those who initiated other psychotropic medications. The rate of myocardial infarction was higher (). Cardiac arrest, ventricular arrhythmia and venous thromboembolism were uncommon events, with rates well below one per 100 person-years in all groups. Owing to the low number of events observed, these event types, as well as stroke and myocardial infarction, were not included in the final analysis.
Death and major medical events leading to hospital admission within 180 days after start of psychotropic medication, by class of medication
The time from treatment initiation to occurrence of events is shown in . The corresponding rate ratios (RRs) are shown in . Patients who initiated conventional antipsychotics had a higher risk of noncancer-related death than users of atypical antipsychotics (RR 1.47, 95% CI 1.14–1.91), as well as an increased risk of femur fracture (1.61, 95% CI 1.03–2.51). The RR for pneumonia (1.03, 95% CI 0.62–1.69) and heart failure (0.91, 95% CI 0.41–2.01) were near null.
Unadjusted Kaplan–Meier estimates of the probability of no events over time, by psychotropic medication class
Rate ratios for selected health outcomes within 180 days after initiation of therapy with psychotropic medication
Among patients who initiated antidepressants, the associations for noncancer-related death (1.20, 95% CI 0.96–1.50) and femur fracture (1.29, 95% CI 0.86–1.94) were considerably weaker, and the associations for pneumonia (1.09, 95% CI 0.73–1.65) and heart failure (1.04, 95% CI 0.60–1.80) were near null.
Patients who initiated benzodiazepines were at increased risk for noncancer-related death (1.28, 95% CI 1.04–1.58). Virtually no difference was observed in the risk of femur fracture (0.99, 95% CI 0.66–1.51). The RR for pneumonia was 0.85 (95% CI 0.56–1.31). Users of benzodiazepines had an increased risk of admission to hospital for heart failure in the unadjusted analysis (RR 2.59). This association was reduced to 1.54 (95% CI 0.89–2.67) after adjustment for differences in pre-existing cardiovascular disease. When restricting the analyses to users of benzodiazepine medications primarily prescribed for anxiety, we confirmed the findings for noncancer-related death (1.42, 95% CI 1.12–1.81) and heart failure (1.93, 95% CI 1.03–3.60). The result for pneumonia was essentially unchanged; for femur fracture, the RR was 1.23 (95% CI 0.78–1.94).
Results from the initially-treated analysis were consistent with the findings from the as-treated analyses, although the effects tended to be attenuated (Appendix 4, available at www.cmaj.ca/cgi/content/full/cmaj.101406/DC1
). The RR for non-cancer-related death did not differ meaningfully for those with and without a diagnosis of dementia. Restrictions to the subgroup of patients with no prior use of either the treatment or comparator class of medication did not meaningfully affect the associations for any of the outcomes. Likewise, in most cases, analyses using high-dimensional propensity score adjustments yielded no substantive changes. They tended to move the estimates toward the null (). Finally, by way of a sensitivity analysis, we evaluated deaths not expected to be causally related to the exposures. The distribution of causes of death is shown in Appendix 5 (available at www.cmaj.ca/cgi/content/full/cmaj.101406/DC1
). Such causes included certain infectious and parasitic diseases; diseases of the blood and blood-forming organs; diseases of the digestive system; diseases of the genitourinary system; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; and symptoms, signs and abnormal clinical and laboratory findings not classified elsewhere. As expected, we observed effect estimates consistent with a null association for all three comparisons.