Time to Stable Dose of Psychostimulants in Pediatric Patients With ADHD

Study finds younger patients have longer titration periods

Just over half (55%) of patients with attention deficit and hyperactivity disorder (ADHD) achieve a stable medication dose right away, according to a retrospective chart review recently published in the Journal of Pediatric Pharmacology and Therapeutics.

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“Titration can be a frustrating period for patients and their families,” says study co-author Michael Manos, PhD, Director of Cleveland Clinic Children’s ADHD Center for Evaluation and Treatment. “It’s important for pediatricians and behavioral health specialists alike to support families during dose titration, to educate about and help manage any side effects, and to promote adherence.”

For purposes of this study, stable dose was considered achieved when the dose was unchanged from that which was originally prescribed. The study assessed time to stable dose in 500 patients, between the ages of 6 and 15, who were placed on psychostimulants for the first time between the years 2010 to 2015. The interquartile range was 0 to 133.8 days, and the maximum number of days to stable dose was 2,282. When looking for possible associations with demographic characteristics, researchers found that patients under the age of 10 had a longer titration period, although time to stable dose was not significantly associated with sex, insurance type or immediate or extended release formulation. There was an increase in time to stable dose for non-white patients, which although not statistically significant may be clinically significant, according to Dr. Manos.

“Using a small dose of stimulant can improve symptoms right away, though sometimes bumping the dose or giving it at a different time of day might be optimal. Unless the prescribing physician is in contact with the family in those first few weeks of a new medication, this opportunity to optimize treatment response might be missed,” Dr. Manos says.

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Strategies for titration

Physicians typically rely on 4 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 week to one month. This method is convenient in a busy practice and is informative to the physician in a general way. The drawback to this method is that it seldom results in optimal treatment. 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 does not ensure optimal treatment, as there still may be room for improvement.
  • Forced-dose titration. This method is often used in clinical trials. The dose is ramped up until side effects occur and is then reduced until the side effects go away. 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 benefit at the higher dose outweighs the side effects and whether side effects can be managed.
  • Blinded placebo trial. Also often used in research, 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 4 four weeks in a forced-dose titration—a placebo capsule with three active medication doses in escalating order, which is typical of outpatient pediatric practice. Placebo capsules are randomly assigned to one of the four weeks, and behavior is monitored over the seven days of administration by teachers and parents. This strategy has benefits similar to those of forced-dose titration, and it further delineates medicine response—both side effects and behavior change—by adding a placebo condition. It is a systematic, monitored “experiment” for parents who are wary or distrustful of ADHD pharmacotherapy, and it has notable benefits. It is also typically useful for teenagers who are initially reluctant to use medicine to treat symptoms of ADHD. It arrives at optimal treatment in a timely manner, usually in about four to five weeks. On the other hand, this approach requires diligence from families, teachers and caregivers during the initiation phase, and it requires consistent engagement of the physician team.

Behavioral therapy should complement medication for ADHD treatment

Many patients have disinformation related to stimulants. They may be overly concerned with side effects, or fear some sort of long-term organ injury, according to Dr. Manos. “Without adequate follow-up, parents may discontinue medication because of mild side effects, which they could possibly manage with the right guidance,” says Dr. Manos.

“Most of the time when new medicines are being tested, people look for a reduction of symptoms. For example, if you have a patient with all nine symptoms of inattention and the medication reduces the presentation of three of those symptoms, then it might be considered a success. With most of these patients, reducing the symptoms of inattention is only part of the equation,” explains Dr. Manos. “In real life, successful or effective treatment for ADHD doesn’t just involve symptom reduction. You can improve symptoms, but that doesn’t necessarily mean the child’s relationships with their parents will improve, or that she’ll see an improvement in social skills. Our goal is to improve the quality of life for the child and those around the child.”

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Dr. Manos recommends combined treatment with stimulant medication and behavioral therapy, based on research and his own observations in Cleveland Clinic Children’s Medication Monitoring Program and Summer Treatment Program.

“Studies show that you can reduce the medication dose when adding in a behavioral intervention, and that by starting with a behavioral intervention you can actually start with a lower dose. Using only one just isn’t as effective.”

“Ideally, medication reduces symptoms so that children may increase their own behavioral repertoire at the same time. A very impulsive child is not going to suddenly have a bunch of friends because impulsivity improves. The child is not going to automatically know how to act with peers. A behavioral intervention that actually teaches social skills and reinforces cooperative behaviors can help set a child up for success.”