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I (MZP) recently started medical school, and one of the first things we learned in our Human Dimension class was to listen to our patients. While this may seem prosaic to seasoned practitioners, I quickly realized the important, real-world consequences of doing so.
Clinicians rightfully presume that when they send a prescription to a pharmacy, the patient will receive what they have ordered or the generic equivalent unless it is ordered “Dispense as written.” Unfortunately, a confluence of increased demand and supply chain disruptions has produced nationwide shortages of generic Adderall extended-release (XR) and Adderall, which are commonly prescribed to patients with attention-deficit/hyperactivity disorder (ADHD).1 While pharmacies should notify patients when they do not have these medications in stock, we have encountered numerous cases where due to shortages, prescriptions for generic dextroamphetamine/amphetamine salts XR or immediate-release (IR) have been filled with the same milligrams of only dextroamphetamine XR or IR, respectively, without notifying the patient or the prescribing clinician. Pharmacies have included several national chains and local independent stores in the New York/New Jersey region.
Over the past several months, we have encountered patients who had been well stabilized on their ADHD medication regimen who began to report anxiety, jitteriness, agitation, fatigue, poor concentration, and/or hyperactivity, and who also reported that their pills “look different.” First, we considered their symptoms could be attributed to a switch between generic manufacturers. However, upon further inspection, we discovered that the medication name printed on the label was different from what had been prescribed. We confirmed this by checking the Prescription Monitoring Program database.
Pharmacists have recently won prescribing privileges for nirmatrelvir/ritonavir (Paxlovid) to treat COVID-19, but they certainly are not permitted to fill prescriptions for psychoactive controlled substances that have different pharmacologic profiles than the medication the clinician ordered. Adderall contains D-amphetamine and L-amphetamine in a ratio of 3:1, which makes it different in potency from dextroamphetamine alone and requires adjustment to the dosage and potentially to the frequency to achieve near equivalency.
Once we realized the issue and helped our patients locate a pharmacy that had generic Adderall XR and Adderall in stock so they could resume their previous regimen, their symptoms resolved.
It is important for all clinicians to add “medication substitution reaction” to their differential diagnosis of new-onset ADHD-related symptoms in previously stable patients.