(P-549) Benzodiazepine Use, Nonmedical Use, and Overdose in the U.S

Background: Benzodiazepines (BZs) are a class of drugs with various therapeutic uses, mainly as sedatives, anxiolytics, and anti-epileptics. They have abuse liability and are schedule IV controlled substances in the U.S. Given ongoing concerns about BZs’ contribution to adverse outcomes related to nonmedical use, dependence, and addiction, it is important to understand the scope, patterns, and trends in BZ dispensing, abuse, and related outcomes.

Objectives: 1) To describe patterns of dispensing of commonly prescribed BZs (alprazolam, clonazepam, diazepam, lorazepam, and temazepam); 2) to describe morbidity and mortality associated with BZ nonmedical use.

Methods: We analyzed Symphony Health data (2013-2019) to examine nationally estimated outpatient utilization patterns. Using the National Poison Data System (2009-2018), we described the frequency of Poison Control Center (PCC) cases involving BZ abuse and the medical outcome severity and route of abuse. Also, we analyzed Drug Involved Mortality (2010-2017) data to quantify overdose deaths (unintentional or undetermined intent), involving BZs.

Results: Approximately 106 million BZ prescriptions were dispensed in 2019, a 16% decrease from 2013. Alprazolam was the most commonly dispensed BZ.
The total number of U.S. PCC abuse cases involving BZs increased from 6,068 in 2009 to 6,596 in 2011, then declined to 4,711 in 2018. In 2018, alprazolam had the highest annual rates of total and single-substance abuse cases among BZs analyzed (11.2 and 4.0 per 10M dosage units dispensed, respectively). Most BZ abuse cases involved the oral route (>95%). Approximately 70% of BZ abuse cases also involved other substances, most commonly, prescription opioids (38.8%), alcohol (31.3%), and stimulants (14.5%). Multiple-substance BZ abuse cases had more severe medical outcomes than single-substance cases, and the distribution of medical outcome severity was generally similar across the BZs analyzed. Moderate effect (43.3%, symptoms that involved some treatments) was the most common medical outcome.
Among BZs analyzed, alprazolam was involved in the highest number of U.S. overdose deaths with unintentional or undetermined intent (33,604), followed by diazepam (12,462) and clonazepam (8,093), from 2010-2017. In 2017, diazepam and alprazolam had the highest rates of overdose deaths per 1 million dosage units dispensed (3.2 and 2.4, respectively), among BZs examined. Polysubstance cases accounted for 98-99% of overdose deaths documenting involvement of a specific BZ.

Conclusions: Morbidity and mortality associated with BZ nonmedical use are substantial and occur most often in the context of polysubstance use, including but not limited to prescription opioids.