Of the 83,959 NH residents included in our study cohort, 8.9% were prescribed a conventional antipsychotic and 91.1% an atypical drug. Subjects in the conventional drug group were more likely to be male and non-white than those in the atypical drug group. They were more likely to have cardiovascular disease and less likely to have psychiatric comorbidities. Both groups were comparable in terms of the severity of cognitive and functional impairment and the presence of diagnosed behavioral problems. Patients using conventional antipsychotics had lower rates of antidepressant and dementia medication use, but higher rates of hypnotics. They also had a higher Charlson index indicating multiple general medical comorbidities. Patients treated with conventional drugs were less likely than patients treated with atypical drugs to reside in a NH located in the northeast region or in an urban setting ().
Selected characteristics for residents initiating antipsychotics during a nursing home stay
Among patients initiating conventional APMs, haloperidol (87%) was by far the most widely used agent. Among patients initiating atypical APMs, risperidone (40%), olanzapine (33%), and quetiapine (23%) were used most frequently. Ziprasidone and aripiprazole, which were introduced in 2001 and 2002 respectively, each represented <3% of atypical APM use in our study population. Overall, patients initiating different atypical APMs resembled one another in terms of demographic and clinical characteristics. Patients treated with risperidone had slightly fewer recorded depression diagnoses, and use of antidepressants and other psychotropic medications. Patients treated with quetiapine had more diagnoses of Parkinsonism than the other groups ().
The overall mean follow-up since cohort entry was 45 days for patients initiating conventional APMs, and 96 days for patients initiating atypical APMs: 13% of patients initiating conventional APMs died, compared with 10% of patients initiating atypical APMs; half of the patients were censored due to a treatment switch or discontinuation, and 15% due to a hospitalization for reasons unrelated to the outcomes. For all event types considered, patients initiating conventional APMs had higher unadjusted rates than patients initiating atypical APMs (). Results of the PS-adjusted Cox regression analyses indicate that patients initiating conventional APM were at increased risk of serious bacterial infection (HR=1.37; 95%CI, 1.17-1.62), and at a decreased risk of cerebrovascular events (0.81; 95%CI, 0.65-1.01). Findings further suggest that patients initiating conventional APMs may be at an increased risk of MI (1.23; 95%CI, 0.82-1.82), hip fracture (1.27; 95%CI, 0.94-1.72), and pneumonia (1.28; 95% CI, 0.87-1.88), but these associations were imprecisely estimated. Results for the conventional PS and the hdPS analyses were consistent ().
Major medical events leading to hospitalization within 180 days after start of antipsychotics*
Hazard Ratios of Study Outcomes within 180 Days
Analyses stratified by dose confirmed the findings for serious bacterial infection (PS-adjusted HR=1.42 (95%CI, 1.10-1.84) for low-dose, and 1.47 (95%CI, 1.13-1.91) for high-dose) and indicated that the lower risk of cerebrovascular events is driven by the high-dose category (1.01 (95%CI, 0.71-1.42) for low-dose and 0.62 (95%CI, 0.42-0.93) for high-dose). Results for the other outcomes are not presented due to the small (<10) event numbers in some dose strata and resulting unstable estimates.
All associations were estimated with risperidone as the reference group. In view of the fact that 87% of residents initiating conventional APMs were treated with haloperidol, the findings for haloperidol mirror those of the class-level analyses shown above.
The mean follow-up in days since cohort entry was 94 for risperidone, 97 for olanzapine, 96 for quetiapine, 99 for aripiprazole, and 92 for ziprasidone. Results from hdPS-adjusted analyses tended to be somewhat closer to the null than those from conventional PS-adjusted analyses. Among patients initiating olanzapine, the associations for MI (hdPS-adjusted HR=1.03; 95%CI, 0.81-1.32), serious bacterial infections (0.99; 95%CI, 0.89-1.09), and hip fracture (1.08; 95%CI, 0.91-1.29) were near null. The HR for cerebrovascular events was 0.91 (95%CI, 0.81-1.02), and for pneumonia 1.20 (95%CI, 0.94-1.53) ().
Among patients initiating quetiapine, the associations for MI (1.02; 95%CI, 0.77-1.34) and pneumonia (1.05; 95%CI, 0.78-1.42) were near null. Patients treated with quetiapine had a lower risk of bacterial infections (0.83; 95%CI, 0.73-0.94). The HR for cerebrovascular events was 0.89 (95%CI, 0.79-1.02), and for hip fracture 1.17 (95%, 0.96-1.43) (). There was no evidence of effect measure modification by dose for either olanzapine or quetiapine ().
Analyses stratified by dose* *: restricted to users of tablets or caplets; H: high dose; L: low dose
Given the few patients treated with aripiprazole and ziprasidone during the study period, there was insufficient information to draw meaningful conclusions for most event types, except a near null association for cerebrovascular events and hip fracture ().
There was no evidence of effect measure modification by the presence of dementia, behavioral disturbances, or delirium for the class level or individual agent analyses (data not shown).
When comparing the risk of major medical events in residents treated with high (>50 mg chlorpromazine equivalents) versus low (≤50 mg) dose of all APMs combined, an increased risk was observed for pneumonia (hdPS-adjusted HR=1.24; 95%CI, 1.00-1.53) and hip fracture (1.28; 95%CI, 1.10-1.49). The associations for MI (1.09; 95%CI, 0.89-1.35), cerebrovascular events (1.11; 95%CI, 1.00-1.22) and serious bacterial infections (1.09; 95%CI, 0.99-1.19) were weaker, but still pointed toward an increased risk (, Panel A). The association for the risk of hospitalization for any of the events considered was 1.12 (95%CI, 1.05-1.19). Results were similar when restricted to all atypical APMs (, Panel B). Results for users of conventional APMs are not presented owing to the small event numbers.
Dose-response analyses* *: Restricted to users of tablets or caplets