Update on the Shortage of Amphetamine Mixed Salts for ADHD

For individuals in the United States with attention-deficit/hyperactivity disorder (ADHD), a nationwide shortage in ADHD medications has presented persistent challenges in managing their symptoms.

In October 2022, the US Food and Drug Administration (FDA) announced a shortage of the immediate release formulation of amphetamine mixed salts.¹ As of April 12, 2023, the FDA’s website showed that the shortage is ongoing and primarily involves the immediate-release formulations of brand-name and generic amphetamine mixed salts.²

Reasons listed for these supply issues include an unprecedented increase in demand for amphetamine mixed salts, as well as a shortage of active ingredients to manufacture the drug.² For several manufacturers, the shortages are expected to be resolved by April 2023.²

While there is a dearth of research regarding these developments, studies have found worsening symptoms and functioning among children and adults with ADHD since the onset of the COVID-19 pandemic,^3,4 and research published in March 2023 found that the rate of ADHD-related visits to family physicians increased from 7.6 to 10.5 patients per 1000 between 2020 and 2021.⁵      

However, it is unclear whether these trends are associated with the increased demand for amphetamine mixed salts.

In articles published in nonscholarly outlets, experts point to the substantial increase in direct-to-consumer, telehealth-based companies that began providing prescriptions for ADHD medications after the start of the pandemic.^6,7 In addition, analyses by Trilliant Health demonstrated a 58.2% increase in amphetamine mixed salts prescriptions from 2018-2022 among US adults aged 22 to 44 years⁸, while no significant changes in prescription rates have been observed in other age groups.⁹      

“In hindsight, it is clear that the emergence of digital mental health platforms enabled significant increases in prescribing, particularly for the Millennial generation,” as stated in the Trilliant Heath report.⁹ “Notably, there are more adults receiving prescription Adderall than there are with a formal ADHD diagnosis.”⁹ 

During the COVID-19 public health emergency, providers were able to prescribe controlled substances through telehealth without an in-person medical evaluation. With the anticipated end of the public health emergency on May 11, 2023, the in-patient requirement is set to revert and patients will no longer be able to obtain controlled substance prescriptions through telehealth.

For clinician perspectives on the amphetamine mixed salts shortage, we interviewed psychiatrist Jaskanwar Batra, MD, MHA, vice chair for clinical affairs for behavioral health services at the Keck School of Medicine at the University of Southern California in Los Angeles, and psychologist Justin Barterian, PhD, clinical assistant professor of psychiatry and behavioral sciences at The Ohio State University Wexner Medical Center in Columbus.

In terms of the possible factors driving the amphetamine mixed salts shortage, what is the role of the relatively new telehealth companies prescribing direct-to-consumer prescriptions for ADHD medications? Also, does there seem to be a general issue with overdiagnosis of ADHD in recent years? 

Dr Barterian: I personally do not know much about the operations of online companies like Cerebral. However, there has been an increase in people obtaining information about ADHD from social media.¹⁰ For instance, social media apps have many influencers who discuss ADHD and how it impacts them. While this information may be destigmatizing and affirming for some subscribers and may help some people who have not previously been diagnosed with ADHD identify symptoms in themselves, it may also cause individuals who do not have ADHD to believe they have the disorder.

Additionally, in research published in 2022, Yeung and colleagues found that over one-half of the information posted by users on Tik Tok about ADHD is misleading.¹⁰ This may cause individuals to draw inaccurate conclusions about their own functioning and potential for having the disorder. 

Attention is a spectrum, and there is a wide range in attentional capacity that falls within the normal range of functioning. ADHD diagnoses and stimulant treatment should be applied for those at the very end of the spectrum who are experiencing substantial impairment that is affecting their lives in multiple domains, such as school, relationships, and employment.

In the past, many were concerned about the overdiagnosis and overtreatment of ADHD, especially in children and adolescents. Recently, however, there seems to be more discussion about underdiagnosis — potentially driven by online content — that may be leading to more individuals pursuing ADHD diagnoses, potentially resulting in overdiagnosis.

What are clinicians doing for patients affected by this shortage? For example, are they calling pharmacies to check inventory, switching therapies?

Dr Batra: As a provider, I work with my patients and the pharmacies to match equivalent medications or dose forms to achieve the correct dose. Our physicians often have to switch doses. For example, a patient may have been taking an extended-release medication at 20 mg a day, once a day. For these patients, during the shortage, we may have to prescribe short-acting 10 mg doses to be taken twice a day.

Some brand-name medications have improved availability at times, and we may have to switch to those when available. In some instances, we may switch to a different medication at an equivalent dose to see if it’s equally effective.   

What are further considerations or suggestions for clinicians regarding this topic? 

Dr Batra: Keck Medicine psychiatrists try to be very careful about making any diagnosis, including ADHD, to ensure that we are providing proper treatment to our patients. If the clinical interview is not clear, we augment that with neuropsychological testing to ensure an accurate diagnosis. In the coming weeks, we will be expanding our use of specific objective testing for ADHD to complement the psychiatrist’s evaluation of our patients.

Dr Barterian: I think it is important for clinicians to remember that ADHD diagnoses should be reserved for those who are experiencing significant impairment in multiple domains of their life. It’s also important to remember that many other psychiatric disorders, such as anxiety and depression, can cause symptoms of inattention. Providers should carefully consider the possibility that symptoms of another psychiatric disorder may be causing symptoms of inattention before providing a diagnosis of ADHD.

What measures are needed to prevent this type of issue from occurring again in the future?

Dr Batra: We are hopeful that manufacturers will be able to produce enough medication to allow patients to be adequately treated for this disorder. As a clinician, I encourage regulators to facilitate transparency about crucial medications for the health of patients and urge patients to work with their physician to discuss diagnosis and treatment options. 

Dr Barterian: In regard to minimizing the potential of misdiagnosing someone with ADHD, clinicians should complete a rigorous ADHD assessment. This should include a thorough clinical interview to rule out the potential for other mental health disorders causing ADHD symptoms, as well as standardized ratings of behavior, multiple sources of data, and collateral information of functioning such as report cards, transcripts, and performance reviews from work. With better assessment, patients can receive treatment that will adequately address their underlying causes of inattention symptoms, whether it be anxiety, depression, other mental health disorders, and/or ADHD.