A Patient’s Primer on the Stimulant Medications Used to Treat ADHD
Are stimulants like Ritalin and Concerta really safe? How do they work? What is a good starting dose? What if they don’t work — or carry burdensome side effects? Here, we explain ADHD medications in terms that patients can understand. Become an educated patient and then discuss your options and optimization strategy with your doctor.
EDITORS’ NOTE: The following information is updated annually. The ADHD Medication Guide, developed and maintained by Dr. Andrew Adesman, comprises a comparison chart of FDA-approved stimulants and non-stimulants that is updated more frequently.
Why Use Medication to Treat ADHD?
Stimulant medication is the most recommended form of ADHD treatment for one simple reason: Studies show it to be the most effective. “When adults ask me questions about why they should try medication to manage their ADHD, my answer always comes down to two words: Medication works,” Russell A. Barkley, Ph.D., says. “When you find the right medicine, you can experience substantial improvements in your ADHD symptoms.” Over his four-decade career, Barkley published more than 270 research papers and articles, wrote 23 essential ADHD books, delivered more than 800 addresses, and changed the world’s understanding of what it means to have ADHD and to treat it effectively.
The clinical practice guidelines developed by the American Academy of Child and Adolescent Psychiatry (AACAP) recommend medication as the first-line treatment for ADHD, citing a formal review of 78 studies on the treatment of ADHD, which “consistently supported the superiority of stimulant over the non-drug treatment.”
Even the widely-cited Multi-Modal MTA Cooperative Group Study, which concluded that medication combined with behavior therapy is the optimal treatment of ADHD in school-age children, conceded that “a pharmacological intervention for ADHD is more effective than a behavioral treatment alone.”1
What is Stimulant Medication for ADHD?
The key neurotransmitters deficient in ADHD brains are norepinephrine and dopamine. The primary medications used to treat ADHD stimulate specific cells within the brain to produce more of these deficient neurotransmitters — thus the descriptive label “stimulants.”
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Stimulant medications approved by the FDA deliver only two molecules: methylphenidate and amphetamine. “There is no evidence anywhere to indicate that one molecule is intrinsically better than the other,” says William Dodson, M.D., LF-APA, a board-certified psychiatrist, writer, speaker, and consultant on ADHD medicine.
Methylphenidate-based stimulants include Ritalin, Concerta, Daytrana, Qullivant, Quillichew, Jornay PM, and Azstarys. Amphetamine-based stimulants include Adderall, Vyvanse, and Evekeo.
“The response rates for methylphenidate and amphetamine are about the same,” Dodson says. “When you try both methylphenidate and amphetamine, you get about an 80 to 85 percent robust response rate. Now, that means that if you don’t get a good response with whichever medication you try, don’t give up. Try the other medication.”2
Most people do well on a methylphenidate or an amphetamine, but not both, explains Dodson. He tries both types with each patient to ensure the patient is getting the best outcome possible with ADHD medication. Dodson also recommends long-acting formulations of stimulants rather than short-acting ones. For most patients, the long-acting formulations only require taking one pill a day, provide smoother, more consistent coverage throughout the day, and wear off more gradually, he explains.
[Click to Read: How Safe Are Stimulants?]
What Is the Right Dose?
No test can predict what dose of medication will give a patient the optimal level of benefits with no side effects. What worked best for your brother could be ineffective for you, and vice versa. Every patient’s dose is determined by trial and error.
Genetic testing to measure the alleles that metabolize a medication cannot predict the dose a person will need. Many pediatricians are trained to prescribe a certain number of milligrams per kilogram of a patient’s body mass, but there is no evidence that an ideal dose of ADHD medication correlates in any way to a patient’s size, age, gender, scale scores, or severity of impairment.
Here is what does determine a patient’s optimal dose or ADHD medication:
- Individual metabolism – How medications are absorbed by the GI tract. This changes constantly for kids under 16, so your child’s dosage should be adjusted once a year in August just prior to the beginning of school.
- Individual neurochemistry – How efficiently a medication’s molecules cross the blood-brain barrier from the blood stream into the brain.
Think about ADHD medications as you would eyeglasses. An individual who can’t focus his vision needs to wear glasses; an individual who can’t focus his attention and control his impulses may need ADHD medication. Two people cannot exchange glasses because each prescription is customized to the individual and his unique vision challenges. The notion of high-dose prescription glasses versus low-dose prescription glasses is pretty nonsensical. What we want is the right dose for each individual, and when that right prescription is attained, then the individual sees with 20/20 vision, virtually without side effects.
“ADHD medication is for more than just school,” Dodson says. “It’s for being able to be social, get along with your family, do your homework, meet expectations at work, drive a car at night, and to be safe. The current recommendation is that you take medication wherever there is impairment from ADHD.”
What Is the Wrong Dose?
Optimal doses vary tremendously from person to person. The dosage range approved by the FDA for most ADHD medications covers only about half of all people. Dodson estimates that 6 to 8 percent of children, adolescents, and adults optimize at doses lower than the lowest dosage sizes made, and as many as 40 percent of people optimize at doses higher than those studied and approved by the FDA.
“Physicians should stop viewing dosing from a high- vs. low-dose perspective, and focus instead on fine-tuning a dose to the unique individual. By putting Vyvanse in water, for example, or using liquid formulations such as Quillivant XR, doctors can adjust the dose to lower than the lowest dose made if someone responds well to a small amount,” Dodson says.
Where dosing goes wrong: Patients expect that they should feel stimulated or different in some way.
The rule: The right molecule at the right dose should return a person to normative levels of functioning, not to some artificial amped-up state, and without side effects.
If a person feels different, the dose is too high or too low. “When the dose is off,” Dodson says, “hyperactive people tend to slow down to a crawl; this is commonly known as ‘zombie syndrome.’ Other people get over-stimulated with the wrong dose, and this is called ‘Starbucks syndrome.’ If a patient is experiencing personality changes or feels revved up or slowed down, the dose is typically too high and needs to be decreased. Traditionally, physicians were trained to give the highest dose that a person could tolerate. New research shows that this ‘highest dose’ is too high; the optimum is typically at least two dosage strengths weaker than this threshold.”
What If Stimulant Medications Don’t Work?
Not all children and adults with ADHD respond to or tolerate stimulant medications. For these people, Dodson recommends that doctors turn to the second-line medications for ADHD: the ADHD-specific non-stimulants clonidine and guanfacine. They are alpha-agonists initially developed to treat high blood pressure but are now approved to treat ADHD. They take longer to deliver results than stimulant medications.
The American Academy of Child and Adolescent Psychiatry calls the ADHD-specific non-stimulant Strattera a third-line medication option since it’s moderately effective for elementary-aged children with ADHD,but barely detectable in adolescents and especially adults. Strattera is a selective norepinephrine reuptake inhibitor (SNRI); its structure, models of action, length of time needed to work, and side effects are in many ways similar to a group of medications for mood disorders called “Selective Serotonin Reuptake Inhibitors,” or SSRIs. In fact, Strattera was first studied as a treatment for mood disorders. When it was not found to be successful, it was tried for ADHD. Strattera is approved for use with children aged six years and older, as well as with teens and adults who have ADHD. Safety and effectiveness have not been established in patients under six years of age.
Qelbree is a newer non-stimulant approved for treating ADHD in children and adults in 2021 and 2022, respectively. Its active ingredient, viloxazine hydrochloride, was previously marketed as an antidepressant in Europe. Studies have described viloxazine as a serotonin norepinephrine modulating agent (SNMA).3, 4
Finally, there’s an alternative category of medications sometimes used to treat ADHD, commonly referred to as “off-label” because they weren’t specifically approved to treat ADHD. These include bupropion (Wellbutrin), modafinil (Provigil), tricyclic antidepressants, and amantadine. These are not FDA-approved for the treatment of ADHD, but some literature does support their efficacy in cases where the first-, second-, and third-line treatments have failed.
This article was originally published on February 7, 2017.
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1The MTA Cooperative Group. A 14-Month Randomized Clinical Trial of Treatment Strategies for Attention-Deficit/Hyperactivity Disorder. Arch Gen Psychiatry. 1999;56(12):1073–1086. doi:10.1001/archpsyc.56.12.1073
2Greenhill LL, Abikoff H, Kollins S. 51st Annual Meeting of the American Academy of Child and Adolescent Psychiatry; October 19–24; Washington, DC: 2004. CS Outcome results from the NIMH multi-site Preschool ADHD Treatment Study (PATS)
3Yu, C., Garcia-Olivares, J., Candler, S., Schwabe, S., Maletic, V. (2020). New Insights into the Mechanism of Action of Viloxazine: Serotonin and Norepinephrine Modulating Properties.J Exp Pharmacol. doi: 10.2147/JEP.S256586. PMID: 32943948; PMCID: PMC7473988.
4Edinoff, A.N., Haseeb, A.A., Wagner, J.H. et al. (2021) Viloxazine in the Treatment of Attention Deficit Hyperactivity Disorder.Front. Psychiatry.https://doi.org/10.3389/fpsyt.2021.789982.
