OBJECTIVES: To examine disease-specific associations between antipsychotic dose and duration and all-cause mortality.DESIGN: Retrospective cohort study.SETTING: A 5% random sample of Medicare beneficiaries who had a Minimum Data Set 2.0 clinical assessment completed between 2007 and 2009.PARTICIPANTS: Three mutually exclusive cohorts of new antipsychotic users with evidence of severe mental illness (SMI, n = 5,621); dementia with behavioral symptoms (dementia + behavior) without SMI (n = 1,090); or delirium only without SMI or dementia + behavior (n = 2,100) were identified.MEASUREMENTS: Dose and duration of therapy with antipsychotics were assessed monthly with a 6-month look-back. Dose was measured as modified standardized daily dose (mSDD), with a mSDD of 1 or less considered below or at recommended maximum geriatric dose. Duration was categorized as 30 or fewer, 31 to 60, 61 to 90, and 91 to 184 days for SMI and dementia + behavior and 7 or fewer, 8 to 30, 31 to 90, and 91 to 184 days for delirium. Complementary log-log models with mSDD and duration as time-dependent variables were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality.RESULTS: In all three groups, new antipsychotic users with a mSDD of 1 or less had significantly lower mortality risk (HRSMI  = 0.77, 95% CI = 0.67-0.88; HRdementia+behavior  = 0.52, 95% CI = 0.36-0.76; HRdelirium  = 0.61, 95% CI = 0.44-0.85) than peers with a mSDD greater than 1. Individuals with longer duration of antipsychotic use (91-184 days for SMI and delirium) had significantly lower mortality than those with a short duration of use (?30 days for SMI; ?7 days for delirium). The interaction between dose and duration was statistically significant in the SMI cohort (P < .001).CONCLUSION: Lower mortality was observed with within-recommended dose ranges for dementia + behavior, SMI, and delirium and with long duration of antipsychotic use for the latter two disease groups. Prescribers should monitor antipsychotic dosage throughout the course of antipsychotic treatment and customize dose and duration regimens to an individual's indications.
Aged Antipsychotic Agents