2023 14th Annual NUBE Conference

The use of amphetamine has increased steadily over the past couple decades, with total use in the United States increasing 2.5 times between 2006 and 2016. Since then, use of amphetamine has continued to increase, particularly in the last few years with relaxation of rules for prescribing controlled substances during the pandemic. Although the number of prescriptions for Adderall has stayed constant with pre pandemic levels for those younger than 21 years or older than 45, the number of prescriptions for those ages between 22 and 44 has increased 58% from 2018 to 2022, outpacing the number of ADHD diagnoses in that age group. Insomnia and anxiety are common side effects of stimulants. 30.8% of patients receiving a prescription for a stimulant also received prescriptions for anxiety/sedative/hypnotic medication. The original FDA approval data on amphetamine for attention disorders did not evaluate efficacy or safety of concurrent use with any other medication including benzodiazepines, except acetaminophen. Subsequent efficacy trials of amphetamine for ADHD excluded all other psychoactive medications, including benzodiazepines. One prospective study found that amphetamine reversed the sedative effects of a benzodiazepine, but left substantial deficits in balance, reaction time, memory and insight to impairment. In contrast to the dearth of prospective studies on the efficacy of concurrent amphetamine and benzodiazepines is the wealth of epidemiological studies showing an increased risk of negative outcomes. The combination of amphetamine and a benzodiazepine yielded the highest odds ratio, over 300, for an accident or arrest for erratic driving, higher than any substance alone. Once alprazolam was detected in the blood of an impaired driver, the mostly likely additional substance was amphetamine. If a person combines a sedative with another sedative, they are uncoordinated but also likely to fall asleep. But if a stimulant is combined with a benzodiazepine, subjects are still uncoordinated, but they are wide awake and active, leading to a synergistically greater risk of accidents.The prescription of concurrent amphetamine and alprazolam varies with socioeconomic factors. The prevalence of the combination in each zip code is positively correlated with the fraction of high income households according to data from the Washington State Prescription Monitoring Program (PMP). The total prescription of amphetamine increased with both the fraction of high and low income households. In contrast, the total prescription of alprazolam decreased with the fraction of high income households. The Substance Abuse and Mental Health Data Archive includes surveys on the use of controlled substances during the past year, defined as use prescribed by a physician but also misuse including use of diverted substances. The number of people reporting misuse of both amphetamine and alprazolam exceeds the number prescribed both by a physician for all income brackets.Regardless of source, patients taking this combination are at a synergistically greater risk of a variety of different accidents. This information could be useful in an improved risk assessment in patients presenting with psychiatric emergencies with toxicology screens positive for both amphetamine and benzodiazepines.

Learning Objectives:

1. Estimate the increased risk of motor vehicle accidents in patients with toxicology screens positive for stimulants and benzodiazepines.
2. List activities with increased risk of injury in patients taking concurrent stimulants and benzodiazepines. 
3. Describe the socioeconomic factors in the source of combined stimulants and sedatives.