Per the American Society of Health-System Pharmacists (ASHP) drug shortage detail, both extended-release capsules and immediate-release tablets of amphetamine mixed salts from various manufacturers are currently affected. The estimated reapply dates vary from late December to January 2023, with many unable to provide a release date. Discussion on potential alternatives is lacking in both formulations. [1], [2]
A 2019 review updating on relatively newer stimulant formulations (e.g., orally dissolving tablets, chewable tablets, extended-release liquid formulations, transdermal patches, and novel “beaded” technology) for attention-deficit/hyperactivity disorder (ADHD) briefly discusses the pharmacokinetic properties of amphetamine and methylphenidate. Switching strategies between formulations of amphetamine and methylphenidate are not discussed, except that given the higher potency of amphetamine compared to that of methylphenidate, approximately half to two-thirds of the methylphenidate dose is suggested when converting between the two agents. [3]
A 2012 review article explored the role of stimulant medications, amphetamine, and methylphenidate, in the treatment of ADHD in children and adolescents. General consensus in the guidelines recommends employing a comprehensive, multimodal treatment plan irrespective of which medication is recommended as the first-line agent. The article also reviews available literature comparing the efficacy and safety of methylphenidate and amphetamine for the treatment of ADHD. Due to the paucity of direct, head-to-head, parallel-group studies, the majority of the available evidence was limited to crossover studies (Table 1). Based on included studies, overall, the doses of amphetamine were approximately one-third to one-half the dose of methylphenidate used as specified in Table 1. Although some studies demonstrated methylphenidate was more efficacious than amphetamine and vice-versa, in general, similar responses and rates of adverse events were reported for both medications at the doses studied. Overall, it was recommended that both methylphenidate and amphetamine are appropriate therapies for ADHD, and the choice of simulant should be based on a combination of factors including drug formulation, regimen optimization, monitoring of medication effects, adherence to therapy, and inclusion of behavioral therapy for a multimodal treatment strategy. Non-stimulant medications may also be considered although they may be generally less effective. [4]
An online presentation developed by a psychiatrist and published in the Psychiatric Times discussed switching strategies between different stimulants. Aside from various release mechanisms and numerous stimulant products available, the mainstay of stimulants is categorized as two medications within the formulations, methylphenidate, and amphetamine. Methylphenidate is available in 2 different isomer formulations (50% dex-, 50% levo-methylphenidate; 100% dexmethylphenidate), and amphetamine in 3 formulations (50% dextro-, 50% levo-amphetamine; 75% dextro-, 25% levo-amphetamine; 100% dextroamphetamine). Generally, conversions are considered more precise if the new medication that a patient switches to has the same formulation of isomers as the old one. For instance, Adderall, Adderall XR, Adzenys XR-orally disintegrating tablet (ODT), Dyanavel XR liquid, and Mydayis are listed as 75% dextro-, 25% levo-amphetamine formulation. Given the various duration of action with each agent, the dose may need to be increased if a patient is switched to a stimulant with a longer duration of action; as such, the dose will be spread out over a longer period of time. The author proposed that to convert to a new duration with the same formulation, multiply the old dose by the ratio of (new duration)/(old duration). This will increase the dose if the new duration is longer, and lower the dose if the new duration is shorter. The adjustment ensures that the new medication will deliver the same mg/hour, yet it is only a rough guide. When the stimulant has a range of durations, as with methylphenidate (3-5 hours), the new dose will fall in a range. In this case, clinical judgment will guide a starting dose. [5]
After adjustments for the duration, adjusting for absorption, isomer, and between amphetamine and methylphenidate may still be warranted for certain products. As ODTs generally exhibit different absorption and bioavailability from traditional methylphenidate or amphetamine, a dose conversion from Adderall x 0.63 is suggested when switched to Adzenys ODT. Additionally, conversions among different isomer mixes are all approximate. For amphetamines, despite the fact that the dextro- isomer is more potent, both dextro- and levo- isomers confer therapeutic activity. Therefore, switching among different mixtures of amphetamines is inexact and will need to be personalized for each patient. Rough conversions for switching from an Adderall type (75% dextro) to Evekeo (50% dextro) or Dexedrine/Vyvanse (100%) utilized conversion factors of Adderall x 1.3, Adderall x 0.83, and Adderall x 2.6, respectively. Using proposed converting factors, clinicians may switch Adderall XR 20 mg QAM to Evekeo 26 mg, Dexedrine 16 mg, or Vyvance 52 mg QAM. Notably, the presented conversions are approximations, derived from the potency of their dopaminergic effects and head-to-head studies comparing the stimulants when applicable. [5], [6]
Based on the author's knowledge, switching between the 2 main stimulants, amphetamine, and methylphenidate, remains the most difficult. With a general rule that Adderall is twice as potent as Ritalin, regimens need to be tailored to specific patient needs. Starting the new stimulant at a lower dose and titrating as needed is recommended, especially when the converted doses exceed the maximum recommended dose for ADHD. As the presentation provided conversion factors and switching strategies based on expert opinions and limited supporting literature, use in clinical settings requires close monitoring. [4], [5]