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Adderall Withdrawal Exacerbated by Pharmaceutical Supply Chain Issues

The recent Adderall shortages in the United States have exacerbated withdrawal symptoms and contributed to medication rationing.

On October 12, 2022, the FDA announced a shortage of Adderall and Adderall IR. These shortages have exacerbated withdrawal symptoms and left patients struggling to manage their ADHD by rationing their medication. Understanding how medication shortages stemming from upstream pharmaceutical supply chain issues can compromise care and leave patients vulnerable is increasingly essential.

ADHD

According to the CDC, attention deficit hyperactivity disorder (ADHD) — characterized by difficulty paying attention, impulsive behaviors, and overactivity — is a common neurodevelopmental disorder. Although most patients are diagnosed in childhood, the disease can continue into adulthood.

ADHD Presentations

The CDC states that there are three different presentations of ADHD, depending on the most significant symptoms. Predominantly inattentive presentation is when patients struggle to complete tasks, organize thoughts, and follow instructions or conversations. Additionally, predominantly hyperactive–impulsive presentation comes with an inability to sit still, fidgeting, impulsivity, and excessive talking. The combined presentation combines the two.

Risk Factors and Causes

ADHD causes are not fully understood, but current research suggests that brain injury, genetics, environmental factors, alcohol and tobacco exposure in utero, premature delivery, and low birth weight may be potential causes or risk factors.

Diagnosing ADHD

The diagnostic pathway to ADHD can be convoluted as symptoms may be associated with other conditions such as depression, anxiety, sleep problems, or learning disabilities. According to the CDC, “one step of the process involves having a medical exam, including hearing and vision tests, to rule out other problems with symptoms like ADHD. Diagnosing ADHD usually includes a checklist for rating ADHD symptoms and taking a history of the child from parents, teachers, and sometimes, the child.”

Treating ADHD

The current, adequate treatment of ADHD typically combines behavior therapy and medication. According to the Cleveland Clinic, the premise behind ADHD medication is to increase the levels of certain neurotransmitters in the brain, including dopamine and norepinephrine. Providers and researchers currently understand that increasing dopamine and norepinephrine levels can help increase attention span, reduce hyperactivity and impulsivity, and manage executive dysfunction.

With that in mind, it is crucial to understand that ADHD medication comes in multiple types, and each patient is affected differently.

ADHD medication is divided into two main categories: stimulants and non-stimulants. Non-stimulants only increase the levels of norepinephrine in the brain. According to the Cleveland Clinic, “non-stimulant medications for ADHD take longer to start working than stimulants.”

Stimulants, such as Adderall, are more commonly prescribed than non-stimulants and function by increasing dopamine and norepinephrine levels — two substances that are typically controlled to mitigate the risk of substance use disorders. Stimulants can be broken down into two subcategories: immediate-release and extended-release.

Adderall

According to GoodRx, Adderall — sometimes called Adderall IR or Adderall Immediate Release — is a central nervous system stimulant. Although the FDA has approved Adderall for treating ADHD and narcolepsy, GoodRx states that “it's not exactly known how Adderall IR helps to improve attention and focus, but it's thought to work by raising the levels of chemicals in your brain called norepinephrine, dopamine, and serotonin.”

Dosage and Side Effects

The medication is most commonly dispensed in 5, 7.5, 12.5, 15, 20, and 30 mg tablets. The starting dose for children with ADHD between three and six is usually 2.5 mg once daily. For patients older than six, the starting dose is 5 mg once or twice daily.

Side effects of Adderall may include gastrointestinal issues, appetite changes, sleep difficulties, weight loss, mood swings, irregular heartbeat, high blood pressure, rash, muscle pain, dry mouth, and more.

The Adderall Shortage

As part of investigating and monitoring the shortage, the FDA has spent time communicating with major manufacturers, including Teva Pharmaceuticals. While Adderall is being produced, production rates cannot keep up with supply chain demands. According to the FDA, Teva, in particular, is having intermittent manufacturing delays.

A publication in the New York Times notes that Teva Pharmaceuticals attributed its manufacturing delays to a labor shortage over one year ago. The article states, “a spokeswoman for Teva told The Times that those delays have been resolved, but that the company is now facing ‘a surge in demand,’ which is the predominant cause for backorders.”

Impact of the Shortage

This shortage has left many people unable to get their ADHD medications. The New York Times outlines an anecdote about patients waiting for 25 days or longer on their Adderall prescription.

Fairlee C. Fabrett, PhD, director of training and staff development for the child and adolescent division at McLean Hospital in Massachusetts, told the Times, “The people that depend on the medication for daily functioning, for going to work, for being a good mother, for going to class, are struggling. This is not something to make light of.”

Adderall withdrawal symptoms may include mood swings, irritability, appetite suppression, and suicidal ideations. Additional symptoms such as headaches, jitteriness, fatigue, gastrointestinal issues, and more may also occur.

All patients may not experience withdrawal symptoms; however, patients who have been on the medication longer or take a higher dose are more likely to experience symptoms. Abrupt cessation of Adderall can cause patients’ ADHD symptoms to return more aggressively.

Managing the Shortage

While the shortage continues, patients and their providers look for ways to minimize the fallout. Managing ADHD and withdrawal symptoms can be a significant challenge, and unfortunately, there is no way around withdrawal symptoms. For many patients, they are inevitable.

Providers do recommend maintaining healthy nutrition, hydration, and sleep patterns to prevent further exacerbating the symptoms.

Anish Dube, MD, chair of the American Psychiatric Association’s Council on Children, Adolescents, and Their Families, told the New York Times that patients who do not have medication access are strongly urged to communicate with their prescribing provider and formulate a game plan. He explains that some patients may be able to switch to a different ADHD medication, such as Ritalin or Vyvanse.

Despite the availability of these other options, patients established on Adderall may not respond as well to other medications or may have adverse side effects. According to GoodRx, Adderall and Ritalin are very similar medications. However, the organization notes significant differences in the age recommendations for each disease. While Ritalin is preferred to treat children and adolescents, Adderall is the choice medication for adults with ADHD.

“Once you find your medication and you feel good with it, it’s very hard to change,” Fabrett said in the Times article. “It’s not fair that we’re putting our patients in the position to make these decisions.”

Patients have been left flailing, looking for ways to conserve their medication and ensure they will have it available. Some patients have had to ration or divide their medication and alter the type of pills they take (standard vs extended-release).

The FDA states, “until supply is restored, there are alternative therapies, including the extended-release version of amphetamine mixed salts, available to healthcare professionals and their patients for amphetamine mixed salts’ approved indications. Patients should work with their healthcare professionals to determine their best treatment options.”

Understanding Supply Chain Issues

Supply chain shortages are not unique to Adderall and impact a large portion of the population. In recent years, the medical community has seen shortages in multiple sectors, including scarcity of infant formula and menstrual products.

For a while, pharmaceutical companies and manufacturers attributed these shortages to shipping issues during the COVID-19 pandemic. However, as the world has returned to a new normal, the pharmaceutical supply chain has yet to recover. This begs the question, what contributes to all these supply chain shortages, and how can we address them?

In an article published by NBC News, reporters and healthcare professionals criticize the opacity of the pharmaceutical supply chain, noting that there is very little insight into the reasons behind the Adderall shortage and how to best address it.

Based on patterns and current trajectories, many industry leaders believe that supply chain shortages are inevitable. However, pharmaceutical supply chain transparency may help providers prepare themselves and their patients for future shortages.

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