• Home
  • Store
    • Newsletter Subscriptions
    • Multimedia
    • Books
    • eBooks
    • ABPN SA Courses
    • Social Work Courses
  • CME Center
  • Multimedia
    • Podcast
    • Webinars
    • Blog
    • Psychiatry News Videos
    • Medication Guide Videos
  • Newsletters
    • General Psychiatry
    • Child Psychiatry
    • Addiction Treatment
    • Hospital Psychiatry
    • Geriatric Psychiatry
    • Psychotherapy and Social Work
  • FAQs
  • Med Fact Book App
  • Log In
  • Register
  • Welcome
  • Sign Out
  • Subscribe
Home » Stimulant Dosing Limits
Clinical Update

Stimulant Dosing Limits

August 7, 2023
Chris Aiken, MD and Kelvin Quiñones-Laracuente, MD, PhD.
From The Carlat Psychiatry Report
Issue Links: Editorial Information | PDF of Issue

Chris Aiken, MD. Editor-in-Chief, The Carlat Psychiatry Report. Assistant Professor, NYU Langone Department of Psychiatry. Practicing psychiatrist, Winston-Salem, NC. 

Kelvin Quiñones-Laracuente, MD, PhD. Psychiatry resident, NYU Langone Medical Center.

Drs. Aiken and Quiñones-Laracuente have no financial relationships with companies related to this material.

“Amanda” is an engineering student with ADHD. After six years of treatment, she says her current dose of Adderall XR (40 mg) does not work like it used to. You note that 40 mg daily is the listed FDA maximum daily dosage of Adderall, and you are unsure whether to increase the dose or not.

Stimulant dosing presents a unique challenge. These medications are inherently rewarding, which means we can’t take a purely collaborative approach and let patients guide the dose. On the other hand, the safe upper limits are not always clear despite the strict Schedule II status the DEA has placed the medications in. In this article, we’ll look at where to draw the lines and the risk of dosing too high.

What’s wrong with going higher?

A higher dose raises the risk of abuse and diversion, as well as cardiovascular problems like hypertension, stroke, and myocardial infarction. It may even worsen cognition, either by disrupting sleep or causing a hyperfocused state that makes it difficult for the patient to shift gears and change tasks. 

Psychiatric symptoms like psychosis and mania become more likely as the dose inches up. When patients with narcolepsy took high doses of stimulants (approximately double the FDA maximum), it raised their risk of psychosis (12-fold), psychiatric hospitalization (three-fold), and substance abuse (four-fold), according to a study that compared outcomes in high and low doses (Auger RR et al, Sleep 2005;28(6):667–672).

Animal models flag caution regarding the dosing of stimulants, particularly the amphetamines. Studies with baboons have shown damage in striatal dopaminergic terminals on elevated doses of amphetamines, equivalent to 60 mg/day and above in human dosing (Ricaurte GA et al, J Pharmacol Exp Ther 2005;315(1):91–98). At higher doses, animal studies reveal neurotoxic damage to dopaminergic neurons in the caudate putamen (Moratalla R et al, Prog Neurobiol 2017;155:149–170). 

Amphetamines

The FDA sets the maximum for Adderall (IR or XR) at a dose of 40 mg/day for adult ADHD. However, they allow up to 60 mg/day for more severe cases of ADHD, as well as for narcolepsy. That 40–60 mg max was derived from a large registration trial of adult ADHD. The study compared three doses of Adderall XR (20, 40, and 60 mg/day), and found no significant difference between them in terms of safety and efficacy (Weisler RH et al, CNS Spectr 2006;11(8):625–639). There was some evidence that people with more severe ADHD did better on the higher doses of 40–60 mg, but that finding was limited due to its secondary, “data-fishing” nature.

We recommend thinking of the dose in three zones: the safe zone (below 40 mg/day), the gray zone (40–60 mg/day), and the danger zone (above 60 mg/day). Going up to 60 mg/day may be justified when the symptoms are severe, but you’d want to document their presence on the mental status exam and verify that the ADHD is affecting the patient’s functioning. We are not aware of research justifying a dose above 60 mg/day, which would land in the danger zone.

Higher doses may also be justified when a longer duration is needed. Mydayis (a very extended-release version of Adderall) has a maximum dose of 50 mg, but this leads to similar plasma levels as Adderall XR 40 mg because the dose is spread out over 16 hours instead of 12. When extending the duration, make sure the patient is getting adequate sleep so they are not relying on the stimulant for symptoms of sleep deprivation.

TCPR_Aug2023_Table-Dosing-Guidelines.pngMethylphenidates

For methylphenidate, the FDA gives a clear maximum, although it varies slightly by formulation. That max is 60 mg/day for methylphenidate IR (Ritalin), but higher doses are allowed for products with longer durations such as Concerta (72 mg over 12 hours) and Adhansia (100 mg over 16 hours).

A few methylphenidate products have lower dose caps because more of the drug is absorbed. These include the transdermal formulation (Daytrana is given at half the usual methylphenidate dose) and orally disintegrating tablets (Cotempla ODT is dosed at 86% of the usual dose and Adzenys ODT at 65%).

Dosing in the elderly

Adult ADHD is a relatively new concept, and geriatric ADHD is newer still. The middle-aged patients who started stimulants 20 years ago—when the FDA first approved them in adults—are now entering their retirement years with little data to guide them. There are no controlled trials in patients with ADHD after age 50, but a few observational studies suggest older adults continue to benefit, although at lower doses (eg, average doses of 30 mg/day for methylphenidate and 10 mg/day for amphetamine and dextroamphetamine) (Michielsen M et al, J Atten Disord 2021;25(12):1712–1719).

There are three reasons to consider lowering the dose as patients age. Older adults are more susceptible to the cardiovascular effects and—based on animal data—the neurotoxic effects of stimulants. In animal models, the same dose of amphetamine reached twice the levels in the brains of older rats compared to younger ones, suggesting that older adults may not need as high a dose to achieve a good response (Berman SM et al, Mol Psychiatry 2009;14(2):123–142).

Drug interactions

The amphetamines are a major substrate of CYP2D6, so strong CYP2D6 inhibitors (which include bupropion, duloxetine, fluoxetine, and paroxetine) may push the dose even higher. Most stimulants are not significantly affected by food interactions, but Adderall XR may not be absorbed as well when taken with a large, fatty meal. 

Practical steps

Back to our case. Going beyond 40 mg/day of Adderall would land us in the gray zone for this student. Before taking that step, we should verify that her ADHD is causing significant functional impairment and rule out other causes such as sleep deprivation or depression. Besides raising the dose, evidence also supports augmenting with guanfacine or switching to a different amphetamine mixture (eg, dextroamphetamine, lisdexamfetamine). If—after discussing risks and benefits—we decide to raise the dose, we should track her progress with a rating scale such as the Adult ADHD Self-Report Scale (ASRS-v1.1; www.tinyurl.com/376mav49).

CARLAT VERDICT

With psychostimulants, it’s best to stay within the FDA-approved limits. Slightly higher doses of mixed amphetamine salts (Adderall, up to 60 mg/day) may be needed for patients with severe symptoms, and lower doses are likely safer and just as effective in the elderly.

Related content
A Balanced Approach to Treating ADHD
Stimulants: The Case for Caution

General Psychiatry Clinical Update
KEYWORDS ADHD amphetamines methylphenidate psychopharmacology
    Aiken eic 150x150
    Chris Aiken, MD

    Ketamine Assisted Therapy Part I

    More from this author
    Kelvin Quiñones-Laracuente, MD, PhD.

    More from this author
    www.thecarlatreport.com
    Issue Date: August 7, 2023
    SUBSCRIBE NOW
    Table Of Contents
    Learning Objectives, Adult Autism, TCPR, August 2023
    Stimulant Dosing Limits
    Autism in Adults
    Divorce and Mental Health
    Which SSRI Is Best for Panic Disorder?
    CME Post-Test, Adult Autism, TCPR, August 2023
    DOWNLOAD NOW
    Featured Book
    • MFB7e_Print_App_Access.png

      Medication Fact Book for Psychiatric Practice, Seventh Edition (2024) - Regular Bound Book

      The updated 2024 reference guide covering the most commonly prescribed medications in psychiatry.
      READ MORE
    Featured Video
    • KarXT (Cobenfy)_ The Breakthrough Antipsychotic That Could Change Everything.jpg
      General Psychiatry

      KarXT (Cobenfy): The Breakthrough Antipsychotic That Could Change Everything

      Read More
    Featured Podcast
    • shutterstock_2603816031.jpg
      General Psychiatry

      A Scam for Every Woman, Child, and Man: Part 2

      1 in 3 Americans were victims of online scams in the past year. Even when you know your patient is being scammed, it is hard to pull them out. We speak with Cathy Wilson about...
      Listen now
    Recommended
    • Join Our Writing Team

      July 18, 2024
      WriteForUs.png
    • Insights About a Rare Transmissible Form of Alzheimer's Disease

      February 9, 2024
      shutterstock_2417738561_PeopleImages.com_Yuri A.png
    • How to Fulfill the DEA's One Time, 8-Hour Training Requirement for Registered Practitioners

      May 24, 2024
      DEA_Checkbox.png
    • Join Our Writing Team

      July 18, 2024
      WriteForUs.png
    • Insights About a Rare Transmissible Form of Alzheimer's Disease

      February 9, 2024
      shutterstock_2417738561_PeopleImages.com_Yuri A.png
    • How to Fulfill the DEA's One Time, 8-Hour Training Requirement for Registered Practitioners

      May 24, 2024
      DEA_Checkbox.png
    • Join Our Writing Team

      July 18, 2024
      WriteForUs.png
    • Insights About a Rare Transmissible Form of Alzheimer's Disease

      February 9, 2024
      shutterstock_2417738561_PeopleImages.com_Yuri A.png
    • How to Fulfill the DEA's One Time, 8-Hour Training Requirement for Registered Practitioners

      May 24, 2024
      DEA_Checkbox.png

    About

    • About Us
    • CME Center
    • FAQ
    • Contact Us

    Shop Online

    • Newsletters
    • Multimedia Subscriptions
    • Books
    • eBooks
    • ABPN Self-Assessment Courses

    Newsletters

    • The Carlat Psychiatry Report
    • The Carlat Child Psychiatry Report
    • The Carlat Addiction Treatment Report
    • The Carlat Hospital Psychiatry Report
    • The Carlat Geriatric Psychiatry Report
    • The Carlat Psychotherapy Report

    Contact

    carlat@thecarlatreport.com

    866-348-9279

    PO Box 626, Newburyport MA 01950

    Follow Us

    Please see our Terms and Conditions, Privacy Policy, Subscription Agreement, Use of Cookies, and Hardware/Software Requirements to view our website.

    © 2025 Carlat Publishing, LLC and Affiliates, All Rights Reserved.