Pharmaceutical Supply Chains: A Structural Determinant of Health for Children With ADHD

Abstract

Stimulant medications are a central component of management for youth with attention deficit hyperactivity disorder (ADHD) and their access has been impacted by supply shortages since 2022. Disruptions to treatment can lead to increased morbidity and mortality for youth with ADHD. Factors that contribute to pharmaceutical supply chain shortages include surges in demand, reduced capacity for production or distribution, and failures in coordination. This paper provides an overview of the recent stimulant medication shortage and leverages a framework for building resilience in the supply chain to help pediatric health providers take action and improve health outcomes for for youth with ADHD and their families.

Pharmacotherapy is a mainstay of management for children six years and older with attention deficit-hyperactivity disorder (ADHD) (Wolraich et al., 2019), with stimulant medications recommended as first-line pharmacologic treatment (Cortese, 2020). In 2022, the United States Food and Drug Administration (FDA) first announced the shortage of amphetamine salts products used in the treatment of ADHD (e.g., Adderall) that has disrupted treatment for patients nationwide and remains active as of this writing (Califf & Milgram, 2023; FDA, n.d.). Adverse outcomes associated with untreated ADHD include emotional dysregulation, academic underachievement, adverse social interactions, increased risk of injuries, motor vehicle accidents, suicide, and substance use disorders (Centers for Disease Control and Prevention [CDC], 2024a; Faraone et al., 2021). Supply chain issues that disrupt access to stimulant medications exacerbate health care inequities among children with ADHD, as families with increased resources such as time, money, and greater insurance coverage may be better equipped to mitigate them.

ADHD MANAGEMENT WITH STIMULANT MEDICATIONS

Approximately 9% of children in the United States have or have had a diagnosis of ADHD (Wolraich et al., 2019); an estimated 53% of those use at least one medication for treatment (CDC, 2024a). First-line pharmacologic management includes a stimulant from either the methylphenidate or amphetamine class (Cortese, 2020; Wolraich et al., 2019). Behavioral interventions are recommended as first-line treatment for children aged 4 to 5 years, in combination with stimulant therapy for children aged 6 to 12 years, and are encouraged for adolescents in addition to stimulants if available (Wolraich et al., 2019). Nonstimulant medications (e.g., atomoxetine, guanfacine) are considered second-line treatment and may be used as adjunctive or alternatives if stimulants are not preferred or tolerated (Cortese, 2020).

MEDICAL SUPPLY CHAINS AND ACCESS TO STIMULANT MEDICATIONS

Supply chain is defined as “the network of suppliers that deliver products from raw materials to end customers through either an engineered or transactional flow of information, goods, and money” (Association for Supply Chain Management, 2024, p. 190). Key stakeholders in the medical product supply chain include suppliers of raw materials, producers or manufacturers, distributors, and clinical providers, including prescribing clinicians and pharmacies (National Academies of Sciences, Engineering, and Medicine [NASEM], 2022) (see Figure 1). In response to several medical product supply chain vulnerabilities identified during the COVID-19 pandemic, NASEM (2022) investigated the causes of medical product shortages and proposed ways to enhance the resilience of the supply chain. They concluded that most supply shortages are caused by one or more of the following issues: demand surge, capacity reduction, and/or coordination failure (NASEM, 2022).

FIGURE 1. Typical pharmaceutical supply chain and factors that may contribute to disruption.

Created in BioRender. Keeton, V. (2024) BioRender.com/c70h807. Adapted from National Academies of Sciences, Engineering, and Medicine. 2022. Building resilience into the nation’s medical product supply chains. Washington, DC: The National Academies Press.

Demand Surge

According to a CDC report (Danielson, 2023), there were significant increases in the percentage of people with private insurance receiving prescription stimulants between 2016–2021, with the greatest single-year increase at over 10% for most age groups during 2020–2021. The recent surge has been attributed to greater recognition of symptoms leading to diagnosis during the COVID-19 pandemic, as many individuals experienced a persistent increase in cognitive and emotional stressors in combination with greater access to care via telehealth (Sibley et al., 2023). In early 2020, the Department of Health and Human Services (DHHS) and Drug Enforcement Administration (DEA) jointly approved temporary exceptions to allow greater flexibility in telehealth practices and reduce disruptions in care (DHHS, 2023). This created both an increase in access to healthcare providers to diagnose and treat ADHD, and the ability for those providers to prescribe stimulant medications without an in-person visit (Danielson, 2023; DHHS, 2023).

Capacity Reduction

Despite the increase in demand for stimulant medications in recent years, the original shortage of amphetamine products in 2022 began as a consequence of “intermittent manufacturing delays” by a large producer of these medications (FDA, 2023). This is an example of capacity reduction, an interruption of production processes that decreases supply (NASEM, 2022), and is a more common contributor to medical product shortages (Beleche et al., 2022). Capacity reduction can occur at a number of points along the supply chain, for example if a disruption to factory operations (e.g., weather, disease, war) limits the supply of an active pharmaceutical ingredient, or impedes the producer’s ability to manufacture the drug itself (NASEM, 2022; Socal et al., 2023). Price competition can also contribute to capacity reduction, as producers may decide to stop manufacturing drugs with lower profit margins (Beleche et al., 2022; NASEM, 2022), or costs set by drug wholesalers may influence the distribution of medications to pharmacies (Federal Trade Commission [FTC], 2024).

Regulatory barriers also can contribute to capacity reduction (NASEM, 2022), especially for stimulant medications. Prescription stimulants are designated as Schedule II drugs according to the Controlled Substances Act (DEA, 2022), indicating that they have an accepted medical use and have a high potential for abuse. Regulations associated with the prescription of FDA-approved Schedule II medications are intended to reduce their misuse or diversion, and include education and licensure requirements by prescribers, limits to the quantity and frequency of medications prescribed, additional levels of security for electronic prescribing, and tracking through a state-administered prescription monitoring program (DEA, 2022). Misuse of stimulant medications continues to be a concern in both youth and adult populations (National Institute on Drug Abuse, 2023). In a 2023 national survey, the prevalence of nonmedical use of Adderall was 1.7% among eighth and twelfth graders and 2.1% among tenth graders, although this was lower than 2022 rates (Miech et al., 2024).

The regulation of stimulant medications as controlled substances affects the supply chain at multiple touchpoints. First, the quantity of medications manufactured and produced is limited; aggregate production quotas set by the DEA are forecasted from models of demand to reduce the potential for misuse and diversion by controlling the available supply in circulation (Albert, 2018; DEA, 2024a). This can lead to a capacity reduction, such as if demand surge results in the greater need for a medication than manufacturers are allotted to produce, or if disruption in production by one manufacturer results in increased demand from another that has already met their quota. The FDA and DEA can perform interim reviews and approve an increase in production limits, although this process does take time. Perhaps more concerning is if a manufacturer decides to produce less than their quota without relinquishing their remaining allotment. According to a study by the DEA and FDA, approximately 30% of the quota allotted for amphetamine products in 2022 and 2023 was not produced or shipped, resulting in up to one billion fewer doses available for dispensing (Califf & Milgram, 2023).

Coordination Failure

Coordination failure describes factors that prevent supply from meeting demand even if the quantity of supply is sufficient (NASEM, 2022). Coordination failure can occur at any stage of the supply chain. For example, at the level of the supplier or manufacturer, a natural disaster could prevent delivery of medications from the producer to the distributor. Patients and families may also experience coordination challenges at the level of the provider (prescribing) and pharmacy (dispensing). Controlled substance regulations restrict how much of a stimulant medication can be prescribed and how often, as well as whether it must be prescribed in the context of a patient visit and by a provider the patient has seen before (DEA, 2022). This can result in delays if there are challenges with appointment availability, efficiency of patient-provider communication platforms, or institutional protocols such as whether a covering provider will prescribe a controlled substance on behalf of the patient’s primary health care provider in their absence. Choice of medication may be further constrained by insurance coverage and formulary restrictions (Park et al., 2017; Werble, 2017), which can be especially limiting if supply issues are affecting the availability of one medication but the provider cannot prescribe an alternative without prior authorization. Drug shortages also drive up the cost of medications, which may ultimately limit access for patients who cannot afford higher copays or out-of-pocket costs (Office of the Assistant Secretary for Planning and Evaluation [ASPE], 2023). A recent report demonstrated that retail dispensed drugs increased in price by 14% in the 12 months following a drug shortage (ASPE, 2023).

Once the prescription is sent to a pharmacy, another hurdle in the chain is whether the medication is in stock and eligible for dispensing. Medication stock in pharmacies is in part affected by the demand and capacity issues presented previously, but the quantity of controlled substances kept in stock also may be limited in an attempt to reduce liability for theft or diversion (Qato et al., 2022). Pharmacies also must follow regulations for controlled substances regarding how much medication can be dispensed and when (DEA, 2022), and may be influenced by additional restrictions for coverage put in place by the insurer (Park et al., 2017; Werble, 2017). Automation of prescribing and dispensing management systems used in many pharmacies may contribute to delays if automatic declinations result in additional time and communication to approve medication substitutions.

Implications for Practice, Policy, and Research

In their report, NASEM (2022) proposed four layers of policy and infrastructure measures to increase resilience in the medical product supply chain modeled after emergency response measures: awareness, mitigation, preparedness, and response. Common principles that underpin these recommendations include increased transparency at every step of the supply chain, advanced manufacturing, and robust inventory and capacity management (Park et al., 2023). Governmental and policy agencies have since collaborated on efforts to improve supply chain resilience, including investigating the impact of intermediary purchasing organizations and wholesalers on the pricing and availability of pharmaceutical drugs (FTC, 2024). While the NASEM framework was developed with systemic and structural protections in mind, it also can be adapted to outline the steps that pediatric health care providers can take to avoid or address disruptions in treatment for children with ADHD and their families (see Table 1).

TABLE 1.

Clinical applications of the NASEM framework for building resilience into the medical product supply chain.

	Structural Measures (NASEM, 2022)	Applications to Clinical Practice, Advocacy, and Research
Awareness	Transparency to make data available Analytics to process, compile, and interpret data Communication to report information to appropriate stakeholders	Stay up to date on current shortages through the FDA (https://www.dps.fda.gov/drugshortages) and communicate them to patients Check with institutional and local pharmacies about regional shortages Conduct research on the extent and impact of stimulant medication shortages to inform policy
Mitigation	Reduce the likelihood or magnitude of system disruptions Diversification activities to minimize the risk of total system failure Improve quality control processes	Use shared decision-making with patients to consider alternate therapies Develop workflows or clinical decision tools for ease and consistency with medication substitutions
Preparedness	Inventory stockpiling and capacity buffering Contingency planning and organizational readiness	Discuss risks and benefits of drug holidays to extend supply of medication Promote nonpharmacologic strategies for symptom management Communicate disruptions in treatment to teachers, coaches, and other caregivers Educate patients and families about dangers of counterfeit drugs and illegal online suppliers of stimulants; consider prescribing naloxone
Response	Close supply gaps through reduced demand or increased capacity Prophylactic health protection measures	Consider more frequent patient monitoring and follow-up until disruptions resolve and treatment stabilizes Establish collaborative care partnerships with mental health providers, if not already in place Advocate for improved access and coverage for mental health and social care services Conduct research around case management, patient navigation programs, or other interventions to support patients during shortages

Adapted from National Academies of Sciences, Engineering, and Medicine [NASEM], (2022). Building resilience into the nation’s medical product supply chains. The National Academies Press. https://doi.org/10.17226/26420.

Awareness

As this issue progresses it is vital for health care providers to be aware of potential drug shortages and explain to patients and families how this may impact their access to medications. The FDA website provides a searchable free public database where medications can be searched by their generic name or active ingredient and bulletins regarding critical shortages (FDA, n.d.). At the local level, clinics and providers can communicate with institutional and community pharmacies to understand how nationwide shortages are affecting local supply, as this information may not be publicly available to patients. Health systems with electronic patient communication platforms may also consider sending messages to all patients with an ADHD diagnosis to alert them of shortages and offer suggestions to avoid disruption of care. Researchers can also build awareness by conducting robust investigations to determine the extent and impact of stimulant drug shortages on health outcomes and disseminate their findings to relevant health policy organizations. Pediatric health advocates are essential in building awareness to drive policy change, as the voices of nurses and pediatric experts are critical to communicating practice considerations and effects on patient health outcomes.

Mitigation

Mitigation actions are those that can help avoid an event or reduce the magnitude of its impact (Park et al., 2023). With increased awareness of drug shortages, health care providers can mitigate disruptions in treatment by using shared decision-making with patients and families to consider alternate therapies. This could include prescribing a brand name drug over generic if more supply is available, or choosing an alternate medication from the same or a different class. In any of these cases, it is critical for the prescriber to understand dosage equivalents and potential interactions with other medications when changing to a different medication. The provider must also investigate any additional processes through the patient’s insurance formulary to get authorization for the change. Institutions can assist with this process by developing clinical decision tools or algorithms for clinicians to follow when making medication substitutions, to ensure safety and consistency across providers and avoid delays in renewal requests or other asynchronous prescribing management.

Preparedness

In addition to mitigation, preparatory actions should be taken to reduce negative health and safety effects to patients if a shortage of stimulant medications does disrupt treatment (Park et al., 2023). These measures are especially vital for patients with limited resources or with lower income, who are at greater risk of treatment disruptions during supply shortages (Beleche & Kolbe, 2024). During patient encounters, health care providers should have proactive discussions with patients and families around the risks and benefits of “drug holidays” (Ibrahim & Donyai, 2015) to extend the supply of medication, as well as the use of nonpharmacologic strategies and interventions to support symptom management on days when no medication is available. This may include increasing communication with schools, coaches, and other caregivers around adjusting expectations and accommodations. A letter from a health care provider can be an invaluable way to support these conversations. Providers also may consider increased follow-up of patients with ADHD during critical drug shortages, leveraging telehealth and electronic patient-provider messaging platforms to facilitate monitoring.

It is equally important to educate and prepare patients and families about the dangers of seeking other sources for stimulant medications, including international products or illegal online suppliers (CDC, 2024b; DEA, 2024b). Counterfeit pills may have unknown ingredients that could be ineffective or in some cases, lethal; approximately 70% of pills recovered from the illegal market by the DEA contained lethal doses of fentanyl (CDC, 2024b). As a precaution, health care providers should also provide education around community availablility of naloxone, or prescribe it for patients as a preventive measure (CDC, 2024b).

Response

The care needs of patients with ADHD will continue to require a holistic and proactive response well after the stimulant medication shortage resolves. Health care providers should be attentive to the duration of effects that disruptions to treatment may have for their patients and families, and consider increased monitoring until their treatment stabilizes. This also may be an ideal time to establish nonpharmacologic supports if not already in place, including behavioral interventions and comanagement with mental health providers, as an added measure of crisis prevention should a shortage recur. Advocacy for improved access to and coverage of mental health and social care services will be crucial to this effort, particularly for historically and presently marginalized populations (Kamimura–Nishimura et al., 2023). There also is a need for increased research about the potential impact of case management or patient navigation programs (Budde et al., 2022) on patient outcomes during medication shortages, to inform the design and accessibility of these types of interventions as additional crisis prevention measures.

CONCLUSION

The causes of drug shortages and their subsequent effects on health management are multifactorial and complex. Stimulant medications are an essential component of treatment for most youth with ADHD, and interruptions to care can have significant negative consequences for them and their families. While policy and infrastructure changes will be critical to resolving current and preventing future drug shortages, pediatric health care providers also play an important role in the pharmaceutical supply chain as clinicians and advocates to support equitable care for patients and their families.