Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD

Columbia University, New York, New York, United States
Journal of the American Academy of Child & Adolescent Psychiatry (Impact Factor: 6.35). 11/2006; 45(11):1284-93. DOI: 10.1097/01.chi.0000235077.32661.61
Source: PubMed

ABSTRACT The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD).
The 8-phase, 70-week PATS protocol included two double-blind, controlled phases, a crossover-titration trial followed by a placebo-controlled parallel trial. The crossover-titration phase's primary efficacy measure was a combined score from the Swanson, Kotkin, Atkins, M-Flynn, and Pelham (SKAMP) plus the Conners, Loney, and Milich (CLAM) rating scales; the parallel phase's primary outcome measure was excellent response, based on composite scores on the Swanson, Nolan, and Pelham (SNAP) rating scale.
Of 303 preschoolers enrolled, 165 were randomized into the titration trial. Compared with placebo, significant decreases in ADHD symptoms were found on MPH at 2.5 mg (p<.01), 5 mg (p<.001), and 7.5 mg (p<.001) t.i.d. doses, but not for 1.25 mg (p<.06). The mean optimal MPH total daily dose for the entire group was 14.2 +/- 8.1 mg/day (0.7+/-0.4 mg/kg/day). For the preschoolers (n=114) later randomized into the parallel phase, only 21% on best-dose MPH and 13% on placebo achieved MTA-defined categorical criterion for remission set for school-age children with ADHD.
MPH-IR, delivered in 2.5-, 5-, and 7.5-mg doses t.i.d., produced significant reductions on ADHD symptom scales in preschoolers compared to placebo, although effect sizes (0.4-0.8) were smaller than those cited for school-age children on the same medication.

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    • "Compared to both control groups, NFPP yielded clinically significant reductions in parent-reported ADHD symptoms and conduct problems (oppositional, defiant behaviors), increases in observed on-task behavior, and improved maternal sense of well-being. The improvements in ADHD symptoms were in the range found with stimulants in preschoolers (Greenhill et al., 2006) and persisted to 15 weeks follow-up. A second controlled study found no evidence of efficacy when NFPP was delivered by nonspecialist primary care nurses (Sonuga-Barke, Thompson, Daley, & Laver-Bradbury, 2004). "
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    ABSTRACT: Background The ‘New Forest Parenting Package’ (NFPP), an 8-week home-based intervention for parents of preschoolers with attention-deficit/hyperactivity disorder (ADHD), fosters constructive parenting to target ADHD-related dysfunctions in attention and impulse control. Although NFPP has improved parent and laboratory measures of ADHD in community samples of children with ADHD-like problems, its efficacy in a clinical sample, and relative to an active treatment comparator, is unknown. The aims are to evaluate the short- and long-term efficacy and generalization effects of NFPP compared to an established clinic-based parenting intervention for treating noncompliant behavior [‘Helping the Noncompliant Child’ (HNC)] in young children with ADHD.MethodsA randomized controlled trial with three parallel arms was the design for this study. A total of 164 3-4-year-olds, 73.8% male, meeting DSM-IV ADHD diagnostic criteria were randomized to NFPP (N = 67), HNC (N = 63), or wait-list control (WL, N = 34). All participants were assessed at post-treatment. NFPP and HNC participants were assessed at follow-up in the next school year. Primary outcomes were ADHD ratings by teachers blind to and uninvolved in treatment, and by parents. Secondary ADHD outcomes included clinician assessments, and laboratory measures of on-task behavior and delay of gratification. Other outcomes included parent and teacher ratings of oppositional behavior, and parenting measures. (Trial name: Home-Based Parent Training in ADHD Preschoolers; Registry: Identifier: NCT01320098; URL: http://www/ both treatment groups, children's ADHD and ODD behaviors, as well as aspects of parenting, were rated improved by parents at the end of treatment compared to controls. Most of these gains in the children's behavior and in some parenting practices were sustained at follow-up. However, these parent-reported improvements were not corroborated by teacher ratings or objective observations. NFPP was not significantly better, and on a few outcomes significantly less effective, than HNC.Conclusions The results do not support the claim that NFPP addresses putative dysfunctions underlying ADHD, bringing about generalized change in ADHD, and its underpinning self-regulatory processes. The findings support documented difficulties in achieving generalization across nontargeted settings, and the importance of using blinded measures to provide meaningful assessments of treatment effects.
    Journal of Child Psychology and Psychiatry 10/2014; 56(6). DOI:10.1111/jcpp.12346 · 5.67 Impact Factor
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    • "While stimulant medication is relatively easy to implement and often provides rapid therapeutic benefit, a significant minority of youth with ADHD do not respond to stimulant medication (10–30 %; Goldman et al. 1998) or experience significant side effects that prohibit continued use (\10 %; Graham and Coghill 2008). Additionally, stimulant medications appear less effective for young children with ADHD (Greenhill et al. 2006) and may result in an increased rate of side effects (Wigal et al. 2006). Parental perceptions of stimulant medication's impact on overall health and preference for alternative (non-medication) treatments also limit the use of and compliance with stimulant medication (Chacko et al. 2010)—by some accounts, up to 58 % of parents refuse stimulant medication for their child with ADHD (Krain et al. 2005). "
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and chronic mental health condition that often results in substantial impairments throughout life. Although evidence-based pharmacological and psychosocial treatments exist for ADHD, effects of these treatments are acute, do not typically generalize into non-treated settings, rarely sustain over time, and insufficiently affect key areas of functional impairment (i.e., family, social, and academic functioning) and executive functioning. The limitations of current evidence-based treatments may be due to the inability of these treatments to address underlying neurocognitive deficits that are related to the symptoms of ADHD and associated areas of functional impairment. Although efforts have been made to directly target the underlying neurocognitive deficits of ADHD, extant neurocognitive interventions have shown limited efficacy, possibly due to misspecification of training targets and inadequate potency. We argue herein that despite these limitations, next-generation neurocognitive training programs that more precisely and potently target neurocognitive deficits may lead to optimal outcomes when used in combination with specific skill-based psychosocial treatments for ADHD. We discuss the rationale for such a combined treatment approach, prominent examples of this combined treatment approach for other mental health disorders, and potential combined treatment approaches for pediatric ADHD. Finally, we conclude with directions for future research necessary to develop a combined neurocognitive + skill-based treatment for youth with ADHD.
    Clinical Child and Family Psychology Review 08/2014; 17(4). DOI:10.1007/s10567-014-0171-5 · 4.75 Impact Factor
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    • "Management of ADHD should consider those medication strategies that have been demonstrated to increase the probability of reaching remission (Steele et al. 2006b; Gau et al. 2008a; Chou et al. 2009). Methylphenidate is the best-studied stimulant for ADHD, and a number of studies demonstrate that the remission rates range from 21–56% in ADHD patients treated with immediate-release methylphenidate (IR-MPH) (Greenhill et al. 2006; Swanson et al. 2001), to 44–62% in ADHD children and adolescents treated with osmotic release oral system methylphenidate (OROS-MPH) (Swan 1995; Swanson et al. 2004; Steele et al. 2006b; Gau et al. 2008a). There is no report concerning the remission of amphetamine in patients with ADHD so far in spite of amphetamine having been used in treatment of ADHD for years. "
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    ABSTRACT: The purpose of this study was to identify the optimal dose of osmotic release oral system methylphenidate (OROS-MPH) using a dosage forced-titration scheme to achieve symptomatic remission in children with attention- deficit/hyperactivity disorder (ADHD). We also evaluated the efficacy and safety of, and patient and parent satisfaction with, the change in therapy from immediate-release methylphenidate (IR-MPH) to OROS-MPH over 10 weeks. We recruited 521 children and adolescents aged 6-18 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD, who had received IR-MPH treatments (<70 mg/day) for at least 1 month. The treatment, switched from IR-MPH to OROS-MPH according to a conversion scheme, started with a 6-week forced-titration phase of OROS-MPH to achieve symptomatic remission (defined as a score of 0 or 1 for each of the first 18 ADHD items in the Chinese version of the Swanson, Nolan, and Pelham, Version IV [SNAP-IV]), followed by a 4-week maintenance phase. The global ADHD severity and drug side effects of the participants were evaluated. Parents completed the ratings scales for the ADHD-related symptoms. Patient and parent satisfaction for the OROS-MPH treatment was also assessed. Among the 439 participants with ADHD who completed the trial, 290 participants (66.1%) achieved symptomatic remission. The mean dose of OROS-MPH among participants in remission was 36.7 mg (1.08 mg/kg) per day. Increased efficacy, superior satisfaction, and safety equivalent to that of IR-MPH were demonstrated in intra-individual comparisons from the baseline to the end of study. Determinants for remission included less severe ADHD symptoms (SNAP-IV score < 40), no family history of ADHD, and an appropriate dosage of medication according to the patient's weight. The findings suggest remission as a treatment goal for ADHD therapy by providing an optimal dosage of medication for children and adolescents with ADHD through using an effective and tolerable forced-titration scheme.
    Journal of child and adolescent psychopharmacology 04/2012; 22(3):215-25. DOI:10.1089/cap.2011.0006 · 3.07 Impact Factor
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