Reducing Off-Label Quetiapine Prescribing the Old-Fashioned Way: Snail Mail

Close up of hands opening a letter.
Close up of hands opening a letter.
Despite the associated risk for death and cognitive decline, "off-label" prescribing of antipsychotics in patients with dementia has increased.

The investigators of a study published in JAMA Psychiatry used peer comparison letters to reduce the unwarranted prescription of quetiapine, an antipsychotic that is sometimes prescribed, against guidelines, for dementia.

Quetiapine belongs to a class of antipsychotics approved by the US Food and Drug Administration (FDA) for schizophrenia; bipolar disorder; and in some circumstances, depression. Despite the associated risk for death and cognitive decline, “off-label” prescribing of antipsychotics in patients with dementia has increased, prompting warnings from the FDA, the American Psychiatric Association, and the American Geriatrics Society.

Using data from a Centers for Medicare and Medicaid Services analysis, the researchers included approximately 5% of the highest quetiapine prescribers (N=5055) in family medicine, internal medicine, and general practice. Psychiatric specialists were excluded. Prescribers were randomly assigned 1:1 to receive intervention or placebo letters.

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Prescribers in the intervention arm received 3 letters — in April, August, and October 2015 — that indicated that their quetiapine prescribing was relatively high and under review by the Centers for Medicare and Medicaid Services.

In the 9 months prior to index, prescribers in the intervention arm supplied 97 months of quetiapine; between index and 9-month follow up, they prescribed 82 months, an 11.1% reduction. The control arm saw no significant change, prescribing 96 months of quetiapine during that time period. A second, 2-year follow up saw an overall reduction of 15.6% in prescribers who received intervention letters.

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 in patients who received off-label vs guideline-concordant prescriptions. Analyses showed no significant change in mortality, inpatient admissions, emergency department visits, or psychiatrist outpatient visits.

In patients with low-value indications, the substitution of other antipsychotics, antianxiety medications, sleep aids, or antidepressants was present, although analyses did not indicate that these substitutions were significant. Patients with guideline-concordant prescriptions saw a 39.8% shift to other prescribers.

The investigators pointed out that the letters’ effectiveness may have stemmed, in part, from their novelty, and the repeated use of letters could possibly reduce the effect size in future interventions. Nonetheless, the findings suggested that targeted letters may produce robust, long-lasting decreases in inappropriate prescribing.


Sacarny A, Barnett ML, Le J, Tetkoski F, Yokum D, and Agrawal S. Effect of peer comparison letters for high-volume primary care prescribers of quetiapine in older and disabled adults: a randomized clinical trial [published online August 1, 2018]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2018.1867