Effect of Pharmacist Email Alerts on Concurrent Prescribing of Opioids and Benzodiazepines by Prescribers and Primary Care Managers: A Randomized Clinical Trial

Abstract

Importance: Policy makers have sought to discourage concurrent prescribing of opioids and benzodiazepines (coprescribing) because it is associated with overdose. Email alerts sent by pharmacists may reduce coprescribing, but this intervention lacks randomized evidence.

Objective: To investigate whether pharmacist emails to practitioners caring for patients who recently received opioids and benzodiazepines reduce coprescribing of these medications.

Design, setting, and participants: Randomized clinical trial (intention to treat) conducted in 2019-2021 of patients and their practitioners (prescribers and primary care managers) in the National Capital Region of the Military Health System. Participants were 2237 patients who were recently coprescribed opioids and benzodiazepines. These patients had 789 practitioners eligible for emails.

Interventions: Patients were randomized to email alerts to their practitioners or as-usual care. Clinical pharmacists sent the email alert. Messages were standardized and designed to facilitate coordination between practitioners, increase awareness of guidelines, and provide action steps and resources.

Main outcomes and measures: The primary outcomes were patients' days received of opioids, benzodiazepines, and concurrent opioids and benzodiazepines during the 90 days following enrollment evaluated using 1-sided hypothesis tests. Secondary outcomes included total prescribing of opioids and benzodiazepines by patients' practitioners, including to patients outside the study, to test for broader outcomes on their prescribing.

Results: Of 2237 patients, 1187 were assigned to treatment and 1050 to control; 1275 (57%) were women. Patients received a mean (SD) of 31 (44) days of opioids and 33 (34) days of benzodiazepines in the 90 days before enrollment. There were no detected differences in the primary end points, including patients' receipt of opioids (adjusted difference, 1.1 days; 95% CI, -∞ to 3.0; P = .81), benzodiazepines (adjusted difference, -0.6 days; 95% CI, -∞ to 1.4; P = .30), and opioids and benzodiazepines together (adjusted difference, -0.1 days; 95% CI, -∞ to 0.7; P = .41). Of 789 practitioners, 429 were considered the treatment group, 325 were considered controls, and 35 were excluded. There were no detected differences in practitioners' total prescribing of opioids, benzodiazepines, or both drug classes together.

Conclusions and relevance: In this randomized clinical trial of pharmacist emails to practitioners, email alerts failed to detectably reduce coprescribing, highlighting the value of alternative approaches. Combining randomization with quality improvement activities may help stakeholders seeking evidence-based interventions to encourage guideline-concordant care.

Trial registration: ClinicalTrials.gov Identifier: NCT03887247.

Figure 1.. Flow Diagram of Patients in Study

^aIncludes the small number of patients with practitioners who could not be contacted. Among 1989 patient-practitioner pairs in the email alert group, 50 (2.5%) had email addresses that could not be resolved. For these patients, pharmacists sent the email to the patient’s remaining practitioners with valid addresses. If there were no remaining practitioners, the email was not sent.

Figure 2.. Receipt of Opioids and Benzodiazepines by Control and Treatment Group Patients

Each point represents the mean days of drug receipt by patients in the control group and treatment group during a 15-day period relative to enrollment. Means use inverse probability of treatment weights based on the allocation ratio at the time of enrollment. Each panel considers the days of opioids, benzodiazepines, and overlapping opioids and benzodiazepines, respectively, the patient received during the period. Days of overlapping opioids and benzodiazepines calculated assuming patients start taking prescriptions on the day they fill them and continue taking them for the duration of their days' supply. The vertical line denotes the day of enrollment.

Figure 3.. Prescribing of Opioids and Benzodiazepines by Control and Treatment Group Practitioners

Each point represents the average days of drug supplied by practitioners in the control group and treatment group during a 15-day period relative to enrollment, defined as the date their first patient was enrolled in the study. Practitioners allocated to control or treatment group according to the assignment of their first patient enrolled in the study. Averages use inverse probability of treatment weights based on the allocation ratio at the time of enrollment. Each panel considers the days of opioids, benzodiazepines, and overlapping opioids and benzodiazepines, respectively, the practitioner supplied during the period. Overlapping opioid and benzodiazepine days defined as the number of patient-days to which the practitioner contributed. The vertical line denotes the day of enrollment.