Methylphenidate Dosage for Children With ADHD Over Time Under Controlled Conditions: Lessons From the MTA
ABSTRACT 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.
Full-textDOI: · Available from: Peter S Jensen, Aug 13, 2015
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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. "
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).
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- "Jonkman et al., 2007; Rubia et al., 2011). Although methylphenidate is the first-choice drug for ADHD (Wilens, 2008), it is frequently associated with side effects such as weight loss, insomnia and reduced appetite, as well as a high risk of drug addiction (MTA Cooperative Group, 2004; Vitiello et al., 2001). Thus, therapeutic alternatives to manage ADHD are warranted. "
ABSTRACT: Attention deficit hyperactivity disorder (ADHD) likely involves dopaminergic dysfunction in the frontal cortex and striatum, resulting in cognitive and motor abnormalities. Since both adenosine and dopamine modulation systems are tightly intertwined, we tested if caffeine (a non-selective adenosine receptor antagonist) attenuated the behavioral and neurochemical changes in adolescent spontaneously hypertensive rats (SHR, a validated ADHD animal model) compared to their control strain (Wistar Kyoto rats, WKY). SHR were hyperactive and had poorer performance in the attentional set-shifting and Y-maze paradigms and also displayed increased dopamine transporter (DAT) density and increased dopamine uptake in frontocortical and striatal terminals compared with WKY rats. Chronic caffeine treatment was devoid of effects in WKY rats while it improved memory and attention deficits and also normalized dopaminergic function in SHR. Additionally, we provide the first direct demonstration for the presence of adenosine A(2A) receptors (A(2A)R) in frontocortical nerve terminals, whose density was increased in SHR. These findings underscore the potential for caffeine treatment to normalize frontocortical dopaminergic function and to abrogate attention and cognitive changes characteristic of ADHD.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 05/2012; 23. DOI:10.1016/j.euroneuro.2012.04.011 · 5.40 Impact Factor
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- "After the acute dose–response function was determined, saline was repeatedly administered for at least five consecutive sessions and until choice was comparable to baseline responding. As MPH doses are typically titrated to how an individual responds in the clinical setting (Vitiello et al., 2001), the chronic MPH dose administered to each rat was based on individual results. The acute dose that resulted in increases in larger-reinforcer choice relative to saline evident via visual inspection of individual delay-discounting functions was administered repeatedly for 30 sessions (7 days/week). "
ABSTRACT: Methylphenidate (MPH) is one of the most common therapeutics used for the treatment of attention-deficit/hyperactivity disorder (ADHD), which consists of symptoms of inattention, and/or impulsivity and hyperactivity. Acute administration of MPH has been found to decrease impulsive choice in both humans and nonhuman animals, however, little is known about potential long-term changes in impulsive choice due to chronic administration of MPH. In the present experiment, effects of acute and chronic MPH (1.0-10.0mg/kg) were assessed on impulsive choice in the adult male Spontaneously Hypertensive Rat (SHR) to determine the extent of behavioral changes after chronic MPH exposure. Subjects chose between an immediate single food pellet and three food pellets delivered after a delay that increased within session (0 to 16s). At relatively higher doses during acute and chronic administration, choice maintained by the larger reinforcer was disrupted when there was no delay to either outcome, suggesting that MPH may be affecting stimulus control under the current delay-discounting task. When this disruption was not observed, however, MPH effects were selective in that only one intermediate dose (3.0mg/kg) decreased mean impulsive choice at one delay (8s) following acute administration. The same effect was observed following chronic MPH administration except that the dose was higher (5.6 mg/kg) and the delay was shorter (4s). Chronic administration of MPH did not show any negative indicators (e.g., an increase in impulsive choice) when administration was discontinued.Pharmacology Biochemistry and Behavior 06/2011; 99(4):545-51. DOI:10.1016/j.pbb.2011.05.027 · 2.82 Impact Factor