Abstract

Antipsychotic agents, such as quetiapine fumarate, are frequently overprescribed for indications not supported by clinical evidence, potentially causing harm. To investigate if peer comparison letters targeting high-volume primary care prescribers of quetiapine meaningfully reduce their prescribing. Randomized clinical trial (intent to treat) conducted from 2015 to 2017 of prescribers and their patients nationwide in the Medicare program. The trial targeted the 5055 highest-volume primary care prescribers of quetiapine in 2013 and 2014 (approximately 5% of all primary care prescribers of quetiapine). Prescribers were randomized (1:1 ratio) to receive a placebo letter or 3 peer comparison letters stating that their quetiapine prescribing was high relative to their peers and was under review by Medicare. The primary outcome was the total quetiapine days supplied by prescribers from the intervention start to 9 months. Secondary outcomes included quetiapine receipt from all prescribers by baseline patients, quetiapine receipt by patients with low-value or guideline-concordant indications for therapy, mortality, and hospital use. In exploratory analyses, the study followed outcomes to 2 years. Of the 5055 prescribers, 231 (4.6%) were general practitioners, 2428 (48.0%) were in family medicine, and 2396 (47.4%) were in internal medicine; 4155 (82.2%) were male. All were included in the analyses. Over 9 months, the treatment arm supplied 11.1% fewer quetiapine days per prescriber vs the control arm (2456 vs 2864 days; percentage difference, 11.1% fewer days; 95% CI, -13.1% to -9.2% days; P < .001; adjusted difference, -319 days; 95% CI, -374 to -263 days; P < .001), which persisted through 2 years (15.6% fewer days; 95% CI, -18.1% to -13.0%; P < .001). At the patient level, individuals in the treatment arm received 3.9% (95% CI, -5.0% to -2.9%; P < .001) fewer days of quetiapine from all prescribers over 9 months, with a larger decrease among patients with low-value vs guideline-concordant indications (-5.9% [95% CI, -8.0% to -3.9%] vs -2.4% [95% CI, -4.0% to -0.9%], P = .01 for test that effects were equal for both patient groups). There was no evidence of substitution to other antipsychotics, and 9-month mortality and hospital use were similar between the treatment vs control arms. Peer comparison letters caused substantial and durable reductions in quetiapine prescribing, with no evidence of negative effects on patients. ClinicalTrials.gov identifier: NCT02467933.

Highlights

  • INTERVENTIONS Prescribers were randomized (1:1 ratio) to receive a placebo letter or 3 peer comparison letters stating that their quetiapine prescribing was high relative to their peers and was under review by Medicare

  • There was no evidence of substitution to other antipsychotics, and 9-month mortality and hospital use were similar between the treatment vs control arms

  • E very year, millions of older adults are prescribed atypical antipsychotic agents for off-label use beyond the indications approved by the US Food and Drug Administration (FDA), which are limited to schizophrenia, bipolar disorder, and some cases of depression.[1]

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Summary

OBJECTIVE

To investigate if peer comparison letters targeting high-volume primary care prescribers of quetiapine meaningfully reduce their prescribing. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial (intent to treat) conducted from 2015 to 2017 of prescribers and their patients nationwide in the Medicare program. The trial targeted the 5055 highest-volume primary care prescribers of quetiapine in 2013 and 2014 (approximately 5% of all primary care prescribers of quetiapine). INTERVENTIONS Prescribers were randomized (1:1 ratio) to receive a placebo letter or 3 peer comparison letters stating that their quetiapine prescribing was high relative to their peers and was under review by Medicare. Secondary outcomes included quetiapine receipt from all prescribers by baseline patients, quetiapine receipt by patients with low-value or guideline-concordant indications for therapy, mortality, and hospital use. The study followed outcomes to 2 years

RESULTS
CONCLUSIONS AND RELEVANCE
Key Points
Results
B New quetiapine prescribing by study prescribers 90
B Guideline-concordant patients
Discussion
Limitations
Conclusions
13. American Psychiatric Association
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