Getting the dose just right can be tough...
Patients with attention-deficit/hyperactivity disorder (ADHD) often need to change stimulants, but there are a few things to know to get the dose just right when converting. Images Chris Aiken/Unsplash.
Over 30 simulant products have become available since the release of Benzedrine in 1935. Benzedrine was the branded form of amphetamine that disappeared from the market in the early 1980s, only to be revived as Evekeo in 2014.
Behind the varied release mechanisms that set these products apart, there are essentially only two medications within them: Methylphenidate and amphetamine. In the largest meta-analysis to date, methylphenidate had a slight edge in tolerability, particularly in children, while amphetamine was a little more effective.1 In practice, some patients respond better to one and some to the other, so both are often tried in a course of treatment.
Each stimulant comes in 2 isometric forms, and these isomers differ in their potency despite being mirror images of each other. Methylphenidate is available in 2 different isomer formulations, and amphetamine in 3 formulations. It is essential to know which formulation you are dealing with when converting from 1 stimulant to another. Those conversions are less precise if the new medication has a different formulation of isomers than the old one.
The stimulants also vary in their duration of action, from 3-5 hours with Ritalin to 16 hours with Adhansia and Mydayis. If you are switching to a stimulant with a longer duration of action, you may need to raise the dose because it will be spread out over a longer period of time.
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 milligrams per hour, but 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, and clinical is needed to choose a starting place.
If the new stimulant has the same bioavailability and isomer as the old one, the conversion is complete. Otherwise, there are 1 or 2 more steps.
A few stimulants require a further dosage adjustment because their absorption and bioavailability differ from traditional methylphenidate or amphetamine. Most of these are orally disintegrating tablets (ODTs), although Evekeo ODT has the same bioavailability as regular Evekeo and requires no adjustment. With the exception of Daytrana, these products provide conversion factors in their prescribing information.
The conversion table for Daytrana was developed for a clinical study where 177 children were switched abruptly from oral methylphenidate to the transdermal patch.2 Although the study was successful, 38% of the children required a further increase in their dose, suggesting that the dose conversions in this table are on the conservative side.
Next, you’ll need to adjust for the difference in potency if the new stimulant contains a different formulation of isomers. For methylphenidate, the conversion is simple and described on this slide.
For amphetamines, the dextro- isomer is also the more potent one, but the levo- isomer also contributes to its therapeutic activity. Hence, converting among different mixtures of the amphetamines is inexact and will need to be personalized for each patient.
One of the biggest mistakes a clinician can make in this work is to switch from lisdexamfetamine (Vyvanse) to dextroamphetamine without lowering the dose. Vyvanse’s dose is artificially inflated by the extra lis- (lysine). This amino acid adds to the molecular weight (and milligram dose) but not to the therapeutic activity. Lysine ensures that the drug is inactive (a “prodrug”) until it is cleaved off in the blood stream, ensuring that raw Vyvanse will not produce a “high” if it is snorted or injected. To convert from dextroamphetamine to Vyvanse, multiply the total daily dose by 0.32; to convert in the other direction, multiply by 3.13 (= 1/0.32).
The conversions on this slide are approximations, derived from their potency of their dopaminergic effects and – where possible – head-to-head studies comparing the stimulants.3
The most difficult conversion is when you are switching between the 2 main stimulants. This will require a lot of personalization, but a general rule of thumb is that Adderall is twice as potent as Ritalin.4 That, at least, provides a starting place.
Converting doses is part science and part art. When in doubt, start the new stimulant at a lower dose and titrate as needed.
Above are the maximum recommended doses for ADHD (for some medications, the PDR allows higher doses for narcolepsy).
Cortese S, Adamo N, Del Giovane C, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis.Lancet Psychiatry. 2018;5(9):727-738.
Pharmacology data for stimulants was gathered from the prescribing information for each drug and from the following sources:
Steingard R, Taskiran S, Connor DF, Markowitz JS, Stein MA. New Formulations of Stimulants: An Update for Clinicians. J Child Adolesc Psychopharmacol. 2019;29(5):324-339.
Childress AC, Komolova M, Sallee FR. An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations. Expert Opin Drug Metab Toxicol. 2019;15(11):937-974.