Back to Basics: Stimulant Titration Strategies for ADHD
Douglas Russell, MD
PAL Consultant
For this month’s newsletter we present a guide for the efficient, evidence-based titration of stimulant medications for ADHD. While not a universal standard, multi-dose titration strategies modeled after the MTA study are considered best practice for treating ADHD. During a multi-dose titration, parents are provided with three escalating doses and detailed monitoring instructions in order to determine the most effective and tolerable dose for their individual child.
Why do a multi-dose trial? First, it’s the most efficient way to arrive at an optimal maintenance dose. Long-acting once daily stimulant medications typically exert their effects in under an hour, and last anywhere from 6-12 hours. There is no need to wait weeks before you judge efficacy, such as when prescribing antidepressants. Though a trained observer might be able to make an informed dose change daily, it is best to have parents and teachers observe the child for a few days on a single dose to smooth out any environmental confounders than might influence perception of response. 5 days is generally a good rule of thumb, but I will extend this to 7 days if the child has epilepsy (so parents can observe over the weekend), or if there are other factors that may influence tolerance such as comorbid autism spectrum disorder or young age.
Second, a multi-dose titration accounts for variability in response between individuals. The pharmacodynamics and pharmacokinetics associated with stimulant medications can differ substantially between individuals, and as of now this cannot be predicted with psychogenomic testing. In other words, two age-and-weight-matched children can land on different optimum doses.
Third, multi-dose titrations impart agency to the child’s caregivers, who are likely feeling ambivalent about the prospect of medication treatment. After screening for cardiac problems in the child (“fainting during exercise?”) and 1st degree relatives (“sudden cardiac death in a family member under the age of 45?”), I review potential side effects in detail. I emphasize that they as primary caregivers have the flexibility to decide at each stage of the titration whether to continue with the plan or not. I ask parents to observe their child for signs of efficacy and tolerability at each dose. I make it clear that side effects are dose-dependent and give the option of reducing to the previous dose if significant tolerability issues emerge. Parents tend to appreciate this transparency, flexibility and involvement in shared decision-making.
Evidence suggests that methylphenidate-based agents tend to be better tolerated than amphetamine-based agents in school-aged children. While the MTA study utilized immediate-release methylphenidate, these days we have many once daily long and intermediate duration stimulants to choose from. I typically start with Methylphenidate ER OROS (Concerta). In a child 6 or older, who weighs at least 25kg, without cardiac risk factors, I will prescribe #30 18mg tabs and provide the following instructions to the primary caregiver:
18 mg (one tab) in the morning for 5 days, then
36mg (two tabs) every morning for 5 days, then
54mg (three tabs) every morning for 5 days.
Schedule follow-up in 2-3 weeks to discuss efficacy and tolerability at each dose before settling on an optimal maintenance dose. Roughly equivalent dose titrations for commonly prescribed long acting stimulants are summarized below (note variable potency).
Methylphenidate ER OROS (Concerta): 18mg -> 36mg -> 54 mg
Dexmethylphenidate ER (Focalin XR): 10mg->15mg->20mg
Methylphenidate ER 50/50 (Ritalin LA): 10mg -> 20mg -> 30mg
Methylphenidate ER 30/70 (Metadate CD): 10mg -> 20mg -> 30mg
Amphetamine/Dextroamphetamine ER (Adderall XR): 10mg -> 20mg -> 30mg
Lisdexamfetamine (Vyvanse): 30mg -> 50mg -> 70mg
Lastly, a few pro tips:
- Ritalin LA and Metadate CD are intermediate duration stimulants, lasting about 6-8 hours. If you start with Concerta, but if you find that sleep in an issue, consider a switch.
- Focalin XR, Ritalin LA, Metadate CD, Adderall XR and Vyvanse are all capsules which can be opened and contents sprinkled on preferred foods. This is a good option for children who have difficulty swallowing pills. Quillivant XR (MPH ER liquid), and Daytrana (MPH transdermal patch) are also good options but often require prior authorizations.
- ADHD is highly heritable, so sometimes it is better to keep things as simple as possible for families even if it means veering away from the relative equivalent doses outlined above. For example, in order to avoid having to give two separate prescriptions for Focalin XR, I will sometimes provide #30 5mg capsules and suggest a titration of 5mg -> 10 mg -> 15mg instead. You will be underdosing, but instructions are simpler. Similarly, with Vyvanse I will sometimes provide #30 20mg capsules and suggest 20 mg -> 40mg -> 60mg.
References:
Cortese S 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 Sep;5(9):727-738.
Greenhill LL, Swanson JM, Vitiello B, et al. Impairment and deportment responses to different
methylphenidate doses in children with ADHD: the MTA titration trial. J AmAcad Child Adolesc Psychiatry. 2001;40(2):180-187.
McGough JJ. ADHD. Oxford, UK: Oxford University Press; 2014.
Russell D, Weiss M, Stein MA. A maximum dose for methylphenidate: how much is too much? JAMA Pediatr 2019 Jul 1;173(7):621-622.
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News & Notes
PAL will be closed in observance of the following upcoming holidays:
- Thursday, December 24 - Christmas Eve
- Friday, December 25 - Christmas Day
- Friday, January 1 - New Year's Day
- Monday, January 18 - Martin Luther King Jr. Day
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PAL Spotlight
 Dr. Aditi Sharma has been with PAL since August 2016. She completed her undergraduate education, medical school, and general psychiatry training at the University of Michigan (Go Blue!) in Ann Arbor. She developed an interest in collaborative care during residency, when she realized how helpful it was to support colleagues in other specialties as they were caring for patients with psychiatric needs, and to have their input and support when she was managing medical comorbidities for her own patients. She came to Seattle in June 2014 to complete a fellowship in child and adolescent psychiatry and stayed on after graduation to join the faculty at the University of Washington. In addition to her work in PAL, she is a supervisor in the training clinic at Seattle Children’s, working with residents and fellows.
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Upcoming CME Conferences
Webinars:
Information regarding upcoming webinars will be released soon.
Conferences:
May 21, 2021
This conference has been moved to an online webinar format.
Previously scheduled for Fairbanks, AK
Registration will open in Spring 2021
Conferences run 8:00 AM - 12:30 PM AKST and are FREE to attend.
CME credits are available.
Visit our website for the most updated information on upcoming conferences and to view slides from our previous conferences.
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