For many patients with attention deficit and hyperactivity disorder (ADHD), it takes an average of 5 months to identify the right medication and the correct delivery method and dose. For patients at the Cleveland Clinic’s ACET (ADHD Center for Evaluation and Treatment), this period is shortened to an average of five weeks thanks to the Manos Medication Monitoring Program (M3P).
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“Titration can be a frustrating period for patients and their families,” says study co-author Michael Manos, PhD, Director of the ACET program. “Many are hoping to see a big change in behavior after one dose. If parents don’t have realistic expectations, or if appropriate behavioral modification doesn’t happen in tandem with medications, parents may stop giving the medication. Additionally, there are a lot of misconceptions when it comes to ADHD and medication. Parents might think the medications may turn their kids into zombies, stop eating or have other, severe side effects. Unless the prescribing physician is in contact with the family in those first few weeks of a new medication, this opportunity to optimize treatment might be missed.”
The burden of ADHD
In 2016, 8.4% of children in the U.S. between the ages of 2-17 had been diagnosed with ADHD. Symptoms include hyperactivity and impulsivity (e.g., excessive fidgeting, restlessness, excessive talking, difficulty waiting turns, and interrupting others), and inattention (e.g., easily distracted, forgetful in routine activities, and disorganized with tasks or belongings). In order to make a diagnosis of ADHD, these symptoms must impair the child’s functioning in educational, social or occupational activities.
Generally, optimal treatment includes a combination of medication, behavioral therapy and educational intervention, with goals that include improvement in family and social relationships, rule following, and improved academic performance.
Approaches to titration in ADHD treatment
Physicians typically rely on four strategies to titrate stimulants:
- Prescribe-and-wait. Often, physicians write a prescription and direct the parent to call back or visit the office to relay the child’s response after a specified period, typically one month. If the parent does not call back, the physician may assume the treatment was successful without being certain.
- Dose-to-improvement. In this approach, the physician monitors titration more closely and increases the dose until a positive response is achieved, after which the dose is maintained. This method reduces symptoms, but there still may be room for improvement.
- Forced-dose titration. The dose is ramped up until side effects occur, and is then reduced until the side effects recede. This method often results in optimal dosing, as a forced dose yields a greater reduction in symptoms. However, it requires close monitoring by the physician, with multiple reports from parents and teachers after each dose increase to determine whether or not benefit at the higher dose outweighs the side effects and whether side effects can be managed.
- Blinded placebo trial. This method typically requires a research pharmacy to prepare capsules of stimulant medicine in low, moderate, high and placebo doses. All doses are blinded and given over four weeks in a forced-dose titration. The trial delineates medicine response—both side effects and behavior change—by adding a placebo condition. With this approach, optimization is achieved in about four to five weeks rather than months. However, this approach requires diligence from families, teachers and caregivers during the initiation phase, with consistent engagement of the physician team.
Medication monitoring program
With more than 30 different stimulant delivery systems, finding the right one for each patient can be complex. M3P streamlines the processes of optimizing treatment for patients with ADHD using artificial intelligence (AI). “As a result, we are able to tailor treatment by age and diagnosis across the lifespan,” Dr. Manos says.
M3P is a four- to five- week therapeutic monitoring program that can be used to start or change medicine. The patient receives one week each of a placebo, low, moderate and (at times) high dose of the medicine in a double-blind trial. After the trial, a one-page summary of the results is provided to the primary care physician who manages ongoing care.
The program is designed to help parents and physicians select the best dose of a medicine when treating ADHD and thus to remove the guess work from titrating. It is a safe, systematic and well-monitored method for testing whether a stimulant relieves symptoms of ADHD. The service confirms:
- The stimulant’s efficacy
- The presence or absence of side effects
- “Best” dose or best dose approximation
By removing the usual guesswork involved in selecting the appropriate treatment for patients, M3P achieves symptom management faster, improves the patient experience and increases treatment adherence over time.
The next step
The next step for M3P is the integration of pharmacogenomics, as well as digitization of the data to extend its reach to more patients both within and outside of Cleveland Clinic.
“Data have been missing from ADHD treatment. At Cleveland Clinic, we have collected data from over 25 years in placebo-controlled psychostimulant trials — one patient at a time. These data form the foundation of the M3P. Once automated, we expect this comprehensive ADHD analytics database will change medical practice to create informed outcomes for ADHD and replace physician guesswork in treatment,” concludes Dr. Manos.