The nationwide shortage of stimulant medications approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) remains unresolved nearly 1 year after the US Food and Drug Administration (FDA) first announced a shortage of the short-acting stimulant Adderall (amphetamine mixed salts).1 More recently, supply chain issues have expanded to include other central nervous system (CNS) stimulants used in ADHD treatment, including methylphenidate and lisdexamfetamine.
At the time of this reporting, both immediate-release and extended-release formulations of these medications are affected by the shortage, and extended-release oral suspension amphetamine is the only ADHD stimulant drug that is not currently in shortage, according to the US Food and Drug Administration’s (FDA’s) Drug Shortages database.
The limited availability of these medications has been linked to various factors, including manufacturing delays and below-quota production of amphetamine products that has resulted in a shortage of at least 1 billion doses.2 In addition, there has been an unprecedented increase in the number of Adderall prescriptions that reportedly exceeds the number of individuals with a formal ADHD diagnosis.3
The surge in prescription rates for Adderall and its generic has been partly attributed to unlawful telehealth-based prescriptions from direct-to-consumer companies that increased substantially during the early part of the COVID-19 pandemic. This occurred after the US Drug Enforcement Administration (DEA) suspended the requirement for an in-person evaluation before controlled substances could be prescribed.4
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If a stimulant medication is not available or not an option, CBT and a nonstimulant medication is probably the best option, with the strongest evidence for atomoxetine as a nonstimulant pharmacotherapy.
Michael Bloch, MD, MS, associate professor and director and co-founder of the Pediatric Depression Clinic in the Child Study Center at Yale School of Medicine in New Haven, Connecticut, and Ty Schepis, PhD, professor of psychology at Texas State University in San Marcos spoke with about key considerations regarding appropriate prescribing practices for ADHD medications as well as alternate treatment strategies to be considered as the ADHD drug shortage continues.
Dr Bloch recently co-authored a paper describing best practices for the online assessment and treatment of ADHD.5 Dr Schepis has co-authored studies funded by the FDA and the National Institute on Drug Abuse (NIDA) that investigated the nonmedical use of prescription stimulants and the use of illicit stimulants among adolescents taking prescribed ADHD pharmacotherapy.6,7
What is the proper process for prescribing of ADHD stimulant medications?
Dr Bloch: The proper process for prescribing ADHD stimulant medications involves first doing a thorough evaluation of the patient which would involve personally examining them to verify the diagnosis and doing rating scales of ADHD symptoms. Generally, an ADHD diagnosis requires verification that the symptoms occur in multiple settings such as school, work, home, and during examination.
Dr Schepis: Proper prescribing starts with establishing an ADHD diagnosis and ruling out other potential causes for the person’s symptoms. Sometimes, symptoms of conditions like anxiety disorders overlap with those of ADHD, such as increased distractibility and inattention, so other potential diagnoses need to be ruled out.
If someone comes in with a preexisting ADHD diagnosis, a clinician may still want to gather information and make their own formal diagnosis, given the risks associated with prescription stimulant misuse and diversion. Once the diagnosis is made, the process of finding the ideal medication dose through careful titration is the next step. This can be a longer process, depending on the individual’s medication response and their experience of side effects.
What are some questionable prescribing practices that may occur with stimulant medications for patients with ADHD, and what are some of the risks that may result from improper prescribing?
Dr Bloch: The most questionable prescribing practices that I have heard about are prescribers not personally examining patients or doing a thorough examination. I believe that the time and efficiency pressures of the current practice environment, along with economic incentives in diagnosing and treating patients in less time, has exacerbated the situation.
Dr Schepis: With increased use of telehealth during the COVID-19 public health emergency, there are legitimate concerns that people were prescribed stimulant medication without undergoing a careful ADHD diagnosis. Individuals who receive stimulant medication without an ADHD diagnosis often do not benefit in the ways that they anticipate or hope, and their risk for side effects lead to greater potential harms than benefits from the medication.
With a thorough diagnosis and good communication with the patient, risks from prescribing should be minimal.
What adverse events might occur in patients taking stimulant medications for ADHD, and how should those be addressed in clinical practice?
Dr Bloch: The most common adverse events with stimulants are poor appetite and insomnia. These symptoms improve when the stimulant medication is out of the patient’s bloodstream. These side effects are also a common reason that individuals misuse these medications — so they can lose weight and stay up later, often to study.
Typically, the best way to manage the side effects is to make the patient aware of them and then discuss how to manage the side effects when they occur — for example, lower the dosage, switch formulations, or take the medication earlier.
Immediate-release generic amphetamines have been the most consistently back-ordered ADHD meds.
How should clinicians pivot patients who are taking ADHD medications that are currently unavailable?
Dr Bloch: I tend to encourage my patients to take longer-acting stimulants regularly, so the shortage has certainly affected my patients less than others. I would encourage prescribers to transition patients who benefit from stimulant medications to transition to longer-acting formulations and take them regularly. Many long-acting forms of amphetamine are available, although many of those have gotten caught up in the shortage as well as prescribers are generally all transitioning to the same alterative medications, and that leads to another shortage.
Dr Schepis: Considering a similar amphetamine can be the next step, but transitions from a generic to brand name medication or between different generic amphetamines can lead to restarting the process of titration and dealing with side effects. Switching to a branded amphetamine may not be allowed by insurance or it could be cost-prohibitive, and even then, most generic and branded formulations have subtle differences that can require changes to dosing.
What are some alternate treatment options — including nonpharmacologic strategies — that may be used for patients who can’t access prescribed ADHD drugs affected by the ongoing shortage?
Dr Bloch: A lack of access to stimulant medications for patients who benefit from them can cause a major worsening of their ADHD symptoms. By far, the most effective intervention is to find a suitable replacement medication. There are nonstimulant medications and nonmedication interventions for ADHD, but generally these interventions take several weeks or months to reach full efficacy, so they really are not great short-term replacement for stimulants. That being said, over the long run they can decrease the need for and needed dosage of stimulant medication.
Dr Schepis: There are options that include pharmacologic agents like atomoxetine, clonidine, and guanfacine, but the consensus is that these nonstimulant medications are not as effective as stimulant medications for ADHD. There is a new nonstimulant, viloxazine, but there is not the level of data on it that exists for older nonstimulants.9
For nonpharmacologic treatments, cognitive-behavioral therapy (CBT) is the best behavioral treatment for ADHD, but the consensus is that it needs to be part of a multi-modal treatment regimen that includes medication — ideally, stimulant medication.10,11While I would strongly recommend CBT be part of treatment, it takes weeks to be effective as the patient builds skills and improves coping techniques — that kind of learning and behavior change takes time.
If a stimulant medication is not available or not an option, CBT and a nonstimulant medication is probably the best option, with the strongest evidence for atomoxetine as a nonstimulant pharmacotherapy.
Editor’s note: This Q&A was edited for clarity and length.
