Draft Guidance and Drug Safety Communication Show Center’s Commitment to this Public Health Issue
By: Helen Edelberg, MD, MPH, deputy office director for safety, Office of New Drugs, CDER, and Marta Sokolowska, PhD, deputy center director for substance use and behavioral health, Office of the Center Director, CDER
Stimulants can be approved prescription medications or illegal drugs, such as cocaine and methamphetamine, that speed up bodily systems and make people feel more awake, alert, or energetic. Prescription stimulants, such as Adderall (amphetamine/dextroamphetamine), Ritalin and Concerta (methylphenidate), or Vyvanse (lisdexamfetamine dimesylate), can be used to treat attention-deficient hyperactivity disorder (ADHD), binge-eating disorder, and narcolepsy (uncontrollable episodes of deep sleep), among other conditions. These medications can help manage symptoms such as short attention span and impulsive behavior.
Misuse of prescription stimulants and use of illegal stimulants can give rise to stimulant use disorder. Stimulant use disorder is a pattern of stimulant drug use that causes clinically significant impairment or distress. It can lead to dire health consequences, such as psychiatric problems, seizures, coma, and death.
Unfortunately, overdose fatalities involving stimulants have been increasing every year for over a decade, according to National Institutes of Health analyses of data collected by the Centers for Disease Control and Prevention (CDC). Drug overdose deaths involving cocaine rose steadily from nearly 7,000 in 2015 to almost 16,000 in 2019. From 2019 to 2021, cocaine-involved deaths increased by 54% to over 24,000 deaths. Drug overdose deaths involving other stimulants, primarily methamphetamine, rose from approximately 550 in 1999 to almost 24,000 in 2020, and continued to increase to just under 33,000 deaths in 2021. Many of these stimulant-involved deaths also involved high-potency synthetic opioids, primarily fentanyl.
Overdose fatality rates were generally higher for racial and ethnic minority groups, according to the CDC, with non-Hispanic Black individuals and American Indian/Alaska Native individuals experiencing the highest death rates for overdoses involving cocaine and overdoses involving stimulants other than cocaine, respectively, in 2019.
Draft Guidance: Stimulant Use Disorders: Developing Drugs for Treatment
Given the severity of this public health crisis, CDER has been working with other interested parties on ways to facilitate the development of treatments for stimulant use disorder. We recently published a draft guidance on developing drug treatments for this disorder. As of now, there are no effective medications to treat stimulant use disorder. Drug development is challenging because the disorder is heterogenous, meaning it can involve the use of different types of stimulants in different settings and for different reasons. Finding a medication to treat all patients, or even a subset of patients, with stimulant use disorder is difficult.
The draft guidance provides recommendations for early phase drug development, such as ensuring there are no adverse interactions between the investigational therapy and a stimulant, as it is possible (even likely) that a study participant may be taking both drugs simultaneously.
The draft guidance discusses the benefits and limitations of different methods to assess treatment response, such as biological testing (e.g., testing of urine and other body fluids), patient self-reporting, and capturing periods of non-use. The guidance also describes endpoints that sponsors may consider, including change in pattern of stimulant use and change in disease status using diagnostic criteria, as well as clinical outcome assessments (outcome measures that evaluate how patients feel or function) and changes in mortality and hospitalization rates among people with stimulant use disorder.
We believe this guidance will help pave the way for new drugs to treat stimulant use disorder, and we encourage interested parties to review the draft and provide comment by December 4, 2023.
CDER Updates Warnings to Improve Safe Use of Stimulants
Prescription stimulants can play a role in treating various disorders. They are the most common type of medication to treat ADHD and are also used as therapies for binge-eating disorder and narcolepsy. However, the use of prescription stimulants can lead to misuse and abuse (also called nonmedical use), which can result in addiction, overdose, and death. Therefore, sharing prescription stimulants with people for whom these medications are not prescribed and using one’s prescription stimulant differently than prescribed are serious concerns.
To encourage the safe use of prescription stimulants, CDER announced in May 2023 that it will require changes to all medication labels in this drug class. We are mandating that sponsors add information to the prescribing information that patients should never share their prescription stimulants with anyone. In addition, the Boxed Warning, FDA’s most prominent warning, will describe the risks of misuse, abuse, addiction, and overdose consistently across all prescription stimulant labels. The Boxed Warning will also advise health care professionals to monitor patients closely for signs and symptoms of misuse.
Connection to FDA’s Overdose Prevention Framework
Our efforts on curbing stimulant abuse — through drug development for stimulant use disorder and through fostering safe use of prescription stimulants — align with FDA’s initiatives to prevent overdose, known as the FDA Overdose Prevention Framework. As we continue to fight stimulant use disorder, the lessons we learn can and will be incorporated into the larger framework. Drug overdose has terrible and sometimes irreversible consequences for many people, and our agency is working hard to address this public health crisis.