The rising use of prescription stimulants in the US presents significant safety risks, legal challenges, and supply chain shortages, emphasizing the need for pharmacist involvement in promoting responsible prescribing.
Currently, 6.6% of US adults use prescription stimulants for varying conditions including attention deficit disorder/ attention-deficit/hyperactivity disorder, narcolepsy, cognitive impairment, binge eating disorders, and obesity.1,2 Further, use of prescription stimulants has been trending upward with one study finding that between 2004 and 2019, there was a 5-fold increase in amphetamine prescriptions nationally.3 In Massachusetts, Kim et al reported a 70% increase in stimulant prescriptions during this same time period, with evidence showing that this trend was further exacerbated by the COVID-19 pandemic.4 Factors such as expansion of telehealth services, rising mental health challenges, and limited primary care access all contributed to the increase in stimulant prescriptions, with this rise presenting several safety concerns in how individuals receive health care.1,5,6
Safety concerns surrounding prescription stimulants include amphetamines toxicity, which may result in tachycardia, dysrhythmias, hypertension, aggression, serotonin syndrome, psychosis, and seizures.7 In light of the uptick in prescribed stimulants, resources are being allocated to investigate these safety concerns, with findings showing associated incidences of psychosis and mania with stimulant use, particularly with use of amphetamines. Because of these safety concerns, a more structured approach is needed to safeguard patient outcomes.
A recent study published by Moran et al brings new insights into the complex issues surrounding prescription stimulants, particularly surrounding the incidence of psychosis. The actual mechanism of this remains unclear but it is hypothesized to be related to the increased release of dopamine, a correlation to positive psychosis symptoms.8
Moran et al compared the incidence of stimulant-related psychosis across different groups, adjusting for individual setting, demographic factors, and dosage.8 This work is a continuation of previous research by this author published in 2019, which compared the incidence of psychosis among individuals taking amphetamines vs methylphenidate.9 Moran et al’s most recent study centers around an investigation of the dose-dependent relationship between prescription amphetamines and the incidence of psychosis or mania. The researchers hypothesized an increased risk of psychosis or mania at higher amphetamine doses.
To explore this, they developed a 1:2 case-control study design using electronic medical records between 2005 to 2019 of adults aged 16 to 35 years who were admitted for initial psychiatric hospitalization. They defined case subjects as individuals psychiatrically hospitalized for incident or new-onset psychosis or mania. Control subjects were defined as individuals psychiatrically hospitalized for depression or an anxiety disorder with no history of psychosis or mania. The alternative control subject group was composed of individuals with 3 or more outpatient visits at the same health care system clinic for primary care, pediatrics, or psychiatric care. There were 3 different exposures that the investigators measured: past-month prescription amphetamine use, amphetamine dose-response, and past-month prescription methylphenidate use. Amphemine prescriptions were converted to dextroamphetamine equivalents, and the dose-response was broken into 3 categories of the daily dose of dextroamphetamines: low-dose (<15 mg), medium-dose (15-30 mg), and high-dose (>30 mg).
The findings supported the authors’ hypothesis, indicating a significantly higher likelihood of psychosis or mania among individuals with past-month amphetamine use compared to non-users. In addition, higher amphetamine doses were associated with increased odds of psychosis or mania. At the high-dose level, the odds were over 5 times greater compared to the inpatient control group and over 13 times greater compared to the outpatient control group. The authors concluded their paper with recommendations to minimize prescribing high-dose stimulants, while noting that it remains important to consider trends and obstacles that currently exist for patients around use and access to prescription stimulants.
Adding to the safety concerns of prescription stimulant prescribing, the current guidelines for stimulant use in diagnoses related to attention deficit do not have maximum dose recommendations due to lack of empirical evidence.10 The consequence of unstructured prescribing guidance can lead to a lack of accountability among providers to standardize their practice and promote efficacy and safety at the individual level. Non-stimulant medications, cognitive behavioral therapy, and lifestyle interventions may offer viable alternatives for patients at elevated risk of adverse outcomes with high-dose stimulant use and are indicated for many patients as first-line options.2
The rise in stimulant prescriptions has also led to significant legal concerns. A recent US Department of Justice report highlighted a California-based telehealth company found guilty of distributing dextroamphetamine and amphetamine (Adderall; Teva Pharmaceutical) online and committing health care fraud through fraudulent claims for stimulant prescriptions.11 Nicole Argentieri, the principal deputy assistant attorney general and head of the Justice Department’s Criminal Division, shared that the company, “generated over $100 million in revenue by arranging for the prescription of over 40 million pills” and that this would be the “first criminal drug distribution prosecutions related to telemedicine prescribing through a digital health company.”11
Elise Moore is a class of 2025 PharmD candidate at the University of Minnesota College of Pharmacy.
Katie Bye, PharmD, is a PGY-2 internal medicine preceptor at the Mayo Clinic Medical Center-St. Mary’s Campus.
Megan Leloux, PharmD, BCPP, is a clinical pharmacist at the Mayo Clinic Medical Center-St. Mary’s Campus.
A further complication in stimulant prescribing relates to the national shortage of Adderall and other prescription stimulants. Adderall has been on the National Drug Shortage list since 2022, which is when the Drug Enforcement Agency publicized their prioritization of combating drug diversion and misuse related to stimulant prescriptions, leading to stricter restrictions on the allotment of controlled medications such as stimulants.12 This shortage has disrupted therapy for thousands of patients, leading to a widespread struggle for individuals attempting to obtain their stimulant prescriptions. The CDC cautions of the possible increased risks for injury and overdose accompanying choices related to this challenge.13 Additionally, the change in prescription stimulant access can contribute to misuse, with 1 in 3 adults prescribed stimulants reporting misuse.1
Given the challenges surrounding prescription stimulants and emerging evidence of associated risks, pharmacists are positioned to play a key role in reducing patient harm. The National Institute on Drug Abuse (NIDA) published a research report on the prevention of prescription drug use and recognized pharmacists, “as the first line of defense in recognizing problematic patterns in prescription drug use.”14 The NIDA petition pharmacists to be vigilant of the prescriptions that are being sent and request that they be intentional with patient education around safe drug use based on the current literature, with a focus on the risks surrounding high-dose stimulant use.
Elise Moore is grateful for the mentorship of Katie Bye, PharmD, Megan Leloux, PharmD, BCPP, and Ashley Otto, PharmD, BCPS, while writing this piece. Moore is grateful for the input of Jennifer Riss, PharmD, from a community pharmacist’s perspective. Additionally, Moore is grateful for the clinical input from Zachary Wyman on current trends in psychiatric pharmacy.
As pharmacists and first-line patient advocates, it is our duty to ask for a higher standards of care surrounding prescription stimulant use. This comes in the form of promoting safe practices through intentional patient education, collaborating with other members of the health care team, and supporting policies and practice updates that champion patient safety. The complexities surrounding prescription stimulants have no immediate resolutions. However, it is our responsibility as pharmacists to participate in the conversations surrounding solutions.
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