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Off-label antipsychotic prescribing in nursing homes (NHs) is common and is associated with increased risk of mortality in older adults. Prior large-scale, controlled trials in the NH setting failed to show meaningful reductions in antipsychotic use.To quantify the influence of a large-scale communication training program on NH antipsychotic use called OASIS.This investigation was a quasi-experimental longitudinal study of NHs in Massachusetts enrolled in the OASIS intervention. Participants were residents living in NHs between March 1, 2011, and August 31, 2013. The data were analyzed from December 2015, to March 2016, and from November through December 2016.The OASIS educational program targets all NH staff (direct care and nondirect care) using a train-the-trainer model. The program goals were to reframe challenging behaviors of residents with cognitive impairment as the communication of unmet needs, to train staff to anticipate resident needs, and to integrate resident strengths into daily care plans.This study used an interrupted time series model of facility-level prevalence of antipsychotic medication use, other psychotropic medication use (antidepressants, anxiolytics, and hypnotics), and behavioral disturbances to evaluate the intervention’s effectiveness in participating facilities compared with control NHs in Massachusetts and New York. The 18-month preintervention (baseline) period was compared with a 3-month training period, a 6-month implementation period, and a 3-month maintenance period.This study included 93 NHs enrolled in the OASIS intervention (27 of which had a high prevalence of antipsychotic use) compared with 831 nonintervention NHs. Among OASIS facilities, prevalences of atypical antipsychotic prescribing were 34.1% at baseline and 26.5% at the study end (absolute reduction of 7.6% and relative reduction of 22.3%) compared with a drop of 22.7% to 18.8% in the comparison facilities (absolute reduction of 3.9% and relative reduction of 17.2%). In the OASIS implementation phase, NHs experienced a reduction in antipsychotic use prevalence among OASIS facilities (−1.20%; 95% CI, −1.85% to −0.09% per quarter) greater than that among non-OASIS facilities (−0.23%; 95% CI, −0.47% to 0.01% per quarter), resulting in a net OASIS influence of −0.97% (95% CI, −1.85% to −0.09%; P = .03). A difference in trend was not sustained in the maintenance phase (difference of 0.93%; 95% CI, −0.66% to 2.54%; P = .48). No increases in other psychotropic medication use or behavioral disturbances were observed.Antipsychotic use prevalence declined during OASIS implementation of the intervention, but the decreases did not continue in the maintenance phase. Other psychotropic medication use and behavioral disturbances did not increase. This study adds evidence for nonpharmacological programs to treat behavioral and psychological symptoms of dementia.