Methylphenidate Dosage for Children With ADHD Over Time Under Controlled Conditions: Lessons From the MTA

Columbia University, New York, New York, United States
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 7.26). 03/2001; 40(2):188-96. DOI: 10.1097/00004583-200102000-00013
Source: PubMed


To examine the trajectory of methylphenidate (MPH) dosage over time, following a controlled titration, and to ascertain how accurately the titration was able to predict effective long-term treatment in children with attention-deficit/hyperactivity disorder (ADHD).
Using the 14-month-treatment database of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA), the outcome of the initial placebo-controlled, double-blind, randomized daily switch titration of MPH was compared with the subsequent maintenance pharmacotherapy. Children received monthly monitoring visits and, when needed, medication adjustments.
Of the 198 children for whom MPH was the optimal treatment at titration (mean +/- SD dose: 30.5 +/- 14.2 mg/day), 88% were still taking MPH at the end of maintenance (mean dose 34.4 +/- 13.3 mg/day). Titration-determined dose and end-of-maintenance dose were significantly correlated (r = 0.52-0.68). Children receiving combined pharmacotherapy and behavioral treatment ended maintenance on a lower dose (31.1 +/- 11.7 mg/day) than did children receiving pharmacotherapy only (38.1 +/- 14.2 mg/day). Of the 230 children for whom titration identified an optimal treatment, 17% continued both the assigned medication and dosage throughout maintenance. The mean number of pharmacological changes per child was 2.8 +/- 1.8 (SD), and time to first change was 4.7 months +/- 0.3 (SE).
For most children, initial titration found a dose of MPH in the general range of the effective maintenance dose, but did not prevent the need for subsequent maintenance adjustments. For optimal pharmacological treatment of ADHD, both careful initial titration and ongoing medication management are needed.

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    • "While studies conducted in children and adolescents with stimulants report a dose–response relationship, in adults such a dose–response relationship has not been clearly established [2–4]. Moreover, studies conducted in children also report that treatment optimization with individual dose titration and careful monitoring of adverse events (AEs) provides improvement in ADHD symptoms and a good tolerability profile [5]. For the treatment of adults with ADHD, the European consensus statement recommends individual dose adjustment based on response and tolerability [6]. "
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    Full-text · Article · Jul 2014 · Clinical Drug Investigation
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    • "While MPH is effective in the majority of children in the short term, there is significant variation in individual response to treatment, with a minority not achieving adequate symptom control and others unable to tolerate MPH due to adverse effects [14-16]. Optimization of dose and treatment regimen is needed, therefore, and continued monitoring of response throughout the treatment period is required [16]. Given the range of MPH formulations available and the individualization of therapy that is required to ensure optimal treatment, direct head-to-head studies of long-acting MPH formulations can provide important information about the comparative pharmacokinetics (PK), pharmacodynamics and efficacy of the different formulations. "
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    Full-text · Article · Sep 2013 · BMC Psychiatry
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    • "There was no difference between the placebo response rates for those in MedMgt versus those in Comb (16 in each group) or between those who finished the titration protocol at different times of the year. Twenty-nine of the 32 placebo responders had to go back to taking MPH during the maintenance period (Vitiello et al., 2001). Twenty-six (10% of 256) additional children (9 Comb, 19 MedMgt) showed minimal improvements while taking MPH or placebo, so they were treated with amphetamine and were considered to be nonresponders to MPH. "
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    ABSTRACT: Objective Results of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were analyzed to determine whether a double-blind, placebo-controlled methylphenidate (MPH) titration trial identified the best MPH dose for each child with attention-deficit/hyperactivity disorder (ADHD).
    Full-text · Dataset · May 2013
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