Nonmedical Use of Prescription Stimulants: Risk Factors, Outcomes, and Risk-Reduction Strategies

Background

Stimulant medications (eg, methylphenidate, amphetamine, and lisdexamfetamine) are frequently prescribed for attention-deficit/hyperactivity disorder (ADHD). (1) According to data from the US Drug Enforcement Administration’s Automation of Reports and Consolidated Orders Systems, amphetamine use increased 2.5 times between 2006 to 2016, from 7.9 to 20 tons. In that same time period, methylphenidate use increased from 16.5 tons to 18.6 tons, with peak consumption in 2012 (19.4 tons). (1)

While considered first-line treatments for ADHD, stimulant medications are frequently used for nonmedical purposes.(1) Because stimulant medications induce euphoria and improve alertness and concentration, their potential for abuse, misuse, and diversion is high. (2) Abuse is “the intentional, nontherapeutic use of a drug product or substance, even once, to achieve a desirable psychological or physiological effect,” whereas misuse is “the intentional therapeutic use of a drug product in an inappropriate way and specifically excludes the definition of abuse.” (3) Nonmedical use, which includes both abuse and misuse, is the use of a prescription medication without a prescription, or in a way other than prescribed. (4) Data from the 2016 National Survey on Drug Use and Health determined that an estimated 5.6 million individuals at least 12 years of age misused stimulant medications at some point during the past year. (5)

Stimulant misuse is common among high school and college students. (6-8) A national multicohort study found that 9.5% of high school seniors used stimulant medications for nonmedical uses.6 Data reported by Garnier-Dykstra et al indicated that over a 4-year period, 61% of the college students who participated in the study were offered prescription stimulant medications at least once, and 31% of study participants reported using them for nonmedical purposes. (7) This is particularly concerning because another peer reviewed study by Wilens et al demonstrated that compared with controls (subjects who were not being treated with stimulant medications and had never misused), stimulant medication misusers are at a higher risk for ADHD and/or multiple drug-and/or alcohol-use disorders. (9)

Because of their abuse potential, both the American Academy of Pediatrics (AAP) and the American Academy of Child and Adolescent Psychiatry recommend that clinicians assess for symptoms of substance abuse in adolescent patients receiving stimulant medications. (10,11) According to recently released guidelines from the AAP, “Clinicians should monitor the adolescent’s symptoms and prescription refill requests for signs of misuse or diversion of ADHD medication, including by parents, classmates, or other acquaintances of the adolescent.” (10) 

Rationale for Review by Faraone, et al

To better understand the nonmedical use of prescription stimulants across the lifespan, Faraone et al conducted a systematic review to explore risk factors and motivations for the use of stimulant medications for nonmedical uses. The goal for this review was to add to existing research to assist with identifying high-risk patients and developing more sophisticated approaches to management. (2) 

Methods

A literature review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to examine the epidemiology, risk factors, motivations, and outcomes of the nonmedical use of stimulant medications, specifically methylphenidate and amphetamine.(2) PubMed, PsycINFO, and SCOPUS were searched using ADHD, nonmedical use, illicit use, abuse, misuse, enhancements, stimulants, and other similar terms.2 Studies relating to nonmedical use, diversion, shopping behavior, or malingering of ADHD were included in the analysis.(2) Two reviewers evaluated the studies to ensure inclusion and exclusion criteria were met before the necessary data were extracted. (2)

Results

A total of 86 studies that examined the epidemiology of stimulant nonmedical use and diversion were identified.(2) Self-reported rates of nonmedical use varied considerably among the studies. The majority of studies used the term “nonmedical use,” but others used terms such as misuse and abuse or it was not clearly defined. Reported rates of nonmedical use ranged from 2.1% to 58.7%, depending on definition used, study design, and population studied.(2) In 50% to 90% of nonmedical cases, the stimulant medications were obtained from family or friends.(2) Between 4% to 35% of individuals reported using their own prescribed stimulant medications for nonmedical uses.(2) A total of 20% of adults who reported nonmedical use of stimulants in the past year revealed that they obtained prescriptions fraudulently.(2) College students reported that it was “easy” and rarely difficult to obtain stimulants.(2) The most frequent route of administration was oral (52%-95%), but snorting (nasal route: 7%-48%), smoking (1%-6%), or injecting intravenously (1%-11%) were also noted.(2)

Risk Factors for the Nonmedical Use of Prescription Stimulant Medications

The nonmedical use of prescription stimulant medications was most common in individuals aged 18 to 25 years.(2) Among middle and high school students, those in higher grades were more likely to use stimulant medications for nonmedical uses compared with those in lower grades. Although there were some exceptions, male students were at greater risk for nonmedical use than females, across all age groups.(2) Nonmedical use of stimulants was higher with white students than with Hispanic or African American students.(2) An inverse relationship was observed between grade point average (GPA) and nonmedical use of stimulant medications.(2) Among college students, those belonging to sororities and fraternities were more likely to use stimulants nonmedically than others.(2) Individuals who reported nonmedical use of stimulant medications generally had higher levels of ADHD symptoms versus those who did not report such use, though self-reporting of symptoms may be a confounding factor.(2) Certain conditions were also associated with higher levels of misuse. These included eating disorders and other substance-use disorders (eg, alcohol, marijuana, cocaine, tranquilizers/sedatives, hallucinogens, heroin, inhalants, and pain relievers).(2)

Motivations for the Nonmedical Use of Prescription Stimulant Medications

Academic motivations (cited by 50%-89%) were the primary reason for nonmedical use of stimulants in college students, and 40% of adults reported nonmedical use to improve productivity.(2) Other motivations included recreation, “getting high,” curious/wanting to experiment, boosting the effects of alcohol, augmenting social situations, socialization, enhanced wakefulness, and weight loss.(2)

Undesired Outcomes

The adverse effects of stimulant medications from nonmedical use were generally similar to those reported in clinical trials (eg, headache, stomachache, irritability, feeling sad, reduced appetite, sleep difficulties, and dizziness).(2) The outcomes observed in this systematic review were further divided into medical and academic outcomes.(2)

Medical outcomes associated with prescription stimulant nonmedical use were determined to be burdensome for health care facilities. The authors noted an increased number of emergency department (ED) visits due to nonmedical use of stimulant medications in adults.(2) Amphetamine abuse was associated with high rates of ED visits and a high number of ED visits and admissions to critical care units.(2) Route of administration also played a role in the risk of adverse outcomes.(2) Nasal and intravenous amphetamine abusers had higher rates of death compared with nonabusers.(2) In one study, amphetamine nasal abusers had a mortality rate of 0.5% and intravenous abusers had a 1.2% mortality rate, compared with 0.03% for nonabusers. Compared with nonabusers, the mortality rate was 13x greater for nasal abusers and 22x greater for intravenous abusers.(2)

Academic outcomes were a common motivation for the nonmedical use of stimulant medications; however, data do not correlate with positive academic improvements. This review demonstrated that there were no improvements in academic performance when students without a diagnosis of ADHD used stimulants.(2) Conversely, students who were prescribed stimulant medications did not have lower educational achievement.(2)

Discussion

Five Strategies for Addressing the Nonmedical Use of Stimulant Medications

Misuse of stimulant ADHD medications is associated with safety concerns such as overdose and drug-drug interactions.(8) An unmet need exists for better methods of identifying and mitigating the use of stimulant medications for nonmedical uses.(2,6,8) Five such strategies are discussed below.

I

Prescriber participation and education are essential components of any strategy.

Prescribers not only have the platform to explain the health risks associated with medication abuse, but also the legal consequences of such activity. Utilizing prescribers as allies in adolescent education provides the opportunity to inform students of pertinent judicial considerations in addition to standard clinical concepts.(2) Because of the potential for abuse and diversion, it is important that prescribers screen all patients for comorbid disorders prior to prescribing stimulant medications for ADHD.(6)

II

It is important to proactively identify individuals and households at risk for using stimulant medications for nonmedical purposes.(2) In addition to these risk factors, household diversion should also be considered. Data suggest that homes with children taking ADHD medications are likely to have family members who use stimulant medications for nonmedical purposes.(12)

III

Better identification methods are needed for patients who are malingering. 

Data suggest that it can be difficult for clinicians to detect malingering.(8) When assessing patients for symptoms of ADHD, clinicians need to consider malingering and fully understand the diagnostic criteria for ADHD.8 Improving validity testing could be useful in identifying patients who exaggerate their ADHD symptoms.(2,8)

IV

Increased support and deterrents can be established to minimize the nonmedical
use of stimulant medications.

Tutoring programs for students having difficulty keeping up in school and counseling for those who are struggling with body image are methods aimed to discourage misuse.(13) In addition, incorporating these choices into academic dishonesty policies in high schools and colleges holds individuals accountable for the decisions they make.(2,13) Because students frequently overestimate the nonmedical use of stimulant medications among their peers, correcting this misconception may help reduce such use and reiterate its illegality.(2)

V

Misconstrued beliefs about the benefits of using stimulant medications for nonmedical
uses should be addressed.

The most frequently reported reason for the nonmedical use of stimulant medications among college students was academic enhancement.(2) Although widely believed to improve productivity, attention, and cognitive performance in academic settings, prescription stimulant medications have not been proven to elevate scholastic achievements in individuals without a diagnosis of ADHD.2 Moreover, studies in student populations show an inverse relationship between nonmedical use of stimulant medications and GPA improvements.(2) It is important to highlight these data so that individuals, especially adolescents, understand that the use of stimulant medications to enhance academics is not beneficial in those who do not have ADHD. Challenging this misbelief may reduce the nonmedical use of stimulants.(2) 

Future Directions

When used as prescribed, ADHD stimulants are not associated with an increased risk of substance abuse.(14) However, the misuse and/or abuse of prescription stimulants may lead to a substance use disorder.(15) It is evident that various systemic improvements are needed to evoke necessary changes regarding the nonmedical use of stimulant medications. A combination of techniques is required to best combat this serious issue. Screening tools are needed to help detect patients at risk for nonmedical use, to allow clinicians to direct prevention and treatment efforts to the appropriate patients.(2)

References

1.
Piper BJ, Ogden CL, Simoyan OM, et al. Trends in use of prescription stimulants in the United States and Territories, 2006 to 2016. PloS One. 2018;13(11):e0206100. doi:10.1371/journal.pone.0206100

2.
Faraone SV, Rostain AL, Montano CB, Mason O, Antshel KM, Newcorn JH. Systematic review: nonmedical use of prescription stimulants: risk factors, outcomes, and risk reduction strategies. J Am Acad Child Adolesc Psychiatry. 2020;59(1):100-112. doi:10.1016/j.jaac.2019.06.012

3.
US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Abuse-deterrent opioids— evaluation and labeling guidance for industry. Published April 2015. Accessed June 29, 2020.https://www.fda.gov/media/84819/download

4.
Holt LJ, Looby A. Factors that differentiate prescription stimulant misusers from those at-risk for misuse: expectancies, perceived safety, and diversion. Subst Use Misuse. 2018;53(7):1068-1075. doi:10.1080/10826084.2017.1392984

5.
Substance Abuse and Mental Health Services Administration. Center for Behavioral Health Statistics and Quality. Results from the 2016 National Survey on Drug Use and Health: detailed tables. September 7, 2017. Accessed June 15, 2020. https://www.samhsa.gov/data/sites/default/files/NSDUH-DetTabs-2016/NSDUH-DetTabs-2016.pdf

6.
McCabe SE, West BT. Medical and nonmedical use of prescription stimulants: results from a national multicohort study. J Am Acad Child Adolesc Psychiatry. 2013;52(12):1272-1280. doi:10.1016/j.jaac.2013.09.005

7.
Garnier-Dykstra LM, Caldeira KM, Vincent KB, O’Grady KE, Arria AM. Nonmedical use of prescription stimulants during college: four-year trends in exposure opportunity, use, motives, and sources. J Am Coll Health. 2012;60(3):226-234. doi:10.1080/07448481.2011.589876

8.
Clemow DB, Walker DJ. The potential for misuse and abuse of medications in ADHD: a review. Postgrad Med. 2014;126(5):64-81. doi:10.3810/pgm.2014.09.2801

9.
Wilens T, Zulauf C, Martelon M, et al. Nonmedical stimulant use in college students: association with attention-deficit/hyperactivity disorder and other disorders. J Clin Psychiatry. 2016;77(7):940-947. doi:10.4088/JCP.14m09559

10.
Wolraich ML, Hagan JF Jr, Allan C, et al. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics. 2019;144(4):e20192528. doi:10.1542/peds.2019-2528

11.
Pliszka S. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2007;46(7):894-921. doi:10.1097/chi.0b013e318054e724

12.
Pham T, Milanaik R, Kaplan A, Papaioannou H, Adesman A. Household diversion of prescription stimulants: medication misuse by parents of children with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2017;27(8):741-746. doi:10.1089/cap.2016.0058

13.
Weyandt LL, Oster DR, Marraccini ME, et al. Prescription stimulant medication misuse: where are we and where do we go from here? Exp Clin Psychopharmacol. 2016;24(5):400-414. doi:10.1037/pha0000093

14.
Chang Z, Lichtenstein P, Halldner L, et al. Stimulant ADHD medication and risk for substance abuse. J Child Psychol Psychiatry. 2014;55(8):878-885. doi:10.1111/jcpp.12164

15.
National Institute on Drug Abuse. Drug facts: prescription stimulants. Published June 2018. Accessed June 29, 2020. https://www.drugabuse.gov/sites/default/files/drugfacts-prescriptionstimulants.pdf