Almost 50% of adults taking schedule II stimulants also use other psychiatric drugs

Key takeaways:

• None of the combinations of stimulants and other psychiatric drugs in the study were approved by the FDA.
• A study author told Healio that clinicians should be aware of the risks.

About half of adults who were prescribed schedule II-controlled stimulants were concurrently exposed to other central nervous system-active drugs, many of which have withdrawal effects, complicating discontinuation, researchers reported.

We were concerned to discover that nearly half the prescriptions for amphetamine stimulants were used in combination with antidepressants, antianxiety drugs and other psychiatric drugs,” Thomas J. Moore, AB, a senior associate at Johns Hopkins University Bloomberg School of Public Health, told Healio. “None of these novel drug combinations are FDA approved and not enough is known about either the risks or benefits. The [U.S. Drug Enforcement Agency] classifies these drugs as among the few drugs with highest risks of abuse, misuse, addiction and dependence.”

According to Moore and colleagues, the use of amphetamine and methylphenidate — two central nervous system (CNS) stimulants with effects that have led to medical indications such as narcolepsy, binge eating and depression — has increased among adults in recent years.

“A 2022 study in the electronic health records of 70 million patients in 52 health care organizations reported stimulant prescriptions increased by 250% from 2006 to 2016, with these substances increasingly dispensed to older individuals,” they wrote in BMJ Open.

To examine trends in the use of these stimulants, the researchers analyzed data from Market Scan’s 2019 and 2020 Commercial Claims and Encounters databases. The total study cohort included 9,141,877 adults aged 19 to 64 years.

From Oct. 1, 2019, to Dec. 31, 2020, Moore and colleagues reported that 276,223 (3%) adults had at least one prescription claim for a schedule II stimulant. Of that group, 45.6% had 60 days or more of stimulant use combined with one or more CNS-active drugs, with 24.3% taking two or more CNS-active drugs.

“Approximately one-half (47.6%) of stimulant users were also taking an antidepressant during the year, while nearly one-third (30.8%) were also taking anxiolytics/sedatives/hypnotics,” the researchers wrote.

Additionally, 19.6% received opioid prescriptions.

Moore and colleagues wrote that the findings “add new public health concerns,” one being that most patients (75%) who initiated stimulant use became long-term users.

“This underscores the possible risks of nonmedical use and dependence that have warranted the classification of these drugs as having a high potential for psychological or

physical dependence and their prominent appearance in toxicology drug rankings of fatal overdose cases,” they wrote.

Moore and colleagues also pointed out that the use of amphetamine and methylphenidate extended beyond their primary approved indication as monotherapy for adults with ADHD, and the results suggest that patients “may be getting stimulants or other psychiatric drugs as part of a prescribing cascade.”

“For example, 9.5% of the population getting a potent stimulant of the CNS were also taking alprazolam, an anxiolytic/sedative/hypnotic drug,” they wrote.

Although the data did not indicate whether the exposure to the stimulant or alprazolam came first for patients, because “alprazolam itself has a boxed warning for ‘abuse, misuse, and addiction,’ as well as dependence, and withdrawal reactions, this complicates any discontinuation of either or both drugs,” Moore and colleagues wrote.

The study limitations include an omittance of adults insured in state Medicaid or government programs, and diagnoses could not be linked to specific drug claims and were thus not analyzed, according to the researchers.

Moore said that “clinicians should be alert to the substantial risks of the prescribing cascade.”

“An example: A newly started antidepressant results in too much sedation — a frequent adverse effect. So, an amphetamine stimulant is added. But the stimulant causes insomnia, so alprazolam or another sleep medication is added to the mix,” he said. “Now the patient is taking three drugs, each with different discontinuation symptoms. Stopping one or more of these drugs will be challenging and prolonged. A better solution would be to adjust the antidepressant dose or try an alternative.”