Draft Key Questions
Disposition of Comments Report
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(1) Compare effectiveness and adverse events of interventions (pharmacological, psychosocial, or behavioral, and the combination of pharmacological and psychosocial or behavioral interventions) for preschoolers at high risk for attention deficit hyperactivity disorder (ADHD); (2) compare long-term effectiveness and adverse events of interventions for ADHD among persons of all ages; and (3) describe how identification and treatment for ADHD vary by geography, time period, provider type, and sociodemographic characteristics, compared with endemic prevalence.
MEDLINE®, Cochrane CENTRAL, EMBASE, PsycInfo, and ERIC (Education Resources Information Center) were searched from 1980 to May 31, 2010. Reference lists of included studies and gray literature were searched manually.
Reviewers applied preset criteria to screen all citations. Decisions required agreement between two independent reviewers, with disagreements regarding inclusion or exclusion resolved by a third. The Effective Public Health Practice Project (EPHPP) process was used to evaluate internal validity of publications regarding interventions for preschoolers at high risk of ADHD and long-term outcomes following interventions for ADHD in persons of all ages. Overall strength of the evidence (SOE) was assessed using the GRADE approach, accounting for risk of bias and study design, consistency of results, directness of evidence, and degree of certainty regarding outcomes of interest.
Of included studies, only a subset could be pooled statistically using meta-analytic techniques. For the first objective, we rated as "good" quality eight studies of parent behavior training (PBT) with 424 participants. These demonstrated high SOE for improving child behavior (standardized mean difference [SMD] = ?0.68; 95-percent confidence interval [CI], ?0.88 to ?0.47). A single "good" quality study of methylphenidate (MPH) with 114 preschool children provided low SOE for improving child behavior (SMD = ?0.83; 95-percent CI, ?1.21 to ?0.44). Adverse effects were present for preschool children treated with MPH; adverse effects were not mentioned for PBT.
For the second objective, the majority of studies were open extension trials without continuation of untreated comparison groups. Evidence from the single "good" quality study of MPH demonstrated low SOE for reduction of symptoms, with SMD = ?0.54 (95-percent CI, ?0.79 to ?0.29). Evidence from the single "good" quality study of atomoxetine demonstrated low SOE for reduction of symptoms, with SMD = ?0.40 (95-percent CI, ?0.61 to ?0.18). Evidence from the single "good" quality study of combined psychostimulant medication with behavioral/psychosocial interventions provided low SOE, with SMD = ?0.70 (95-percent CI, ?0.95 to ?0.46). Safety reports for pharmacological interventions derived from observational studies on uncontrolled extensions of clinical trials, as well as from administrative databases, provided inconclusive evidence for growth, cerebrovascular, and cardiac adverse effects. Evidence that psychostimulant use in childhood improves long-term outcomes was inconclusive.
For the third objective, a discussion of contextual issues and factors relating to underlying prevalence and rates of diagnosis and treatment was included. Population-based data were relatively scarce and lacked uniform methods and settings, which interfered with interpretation. The available evidence suggested that underlying prevalence of ADHD varies less than rates of diagnosis and treatment. Patterns of diagnosis and treatment appeared to be associated with such factors as locale, time period, and patient or provider characteristics.
The SOE for PBT as the first-line intervention for improved behavior among preschoolers at risk for ADHD was high, while the SOE for methylphenidate for improved behavior among preschoolers was low. Evidence regarding long-term outcomes following interventions for ADHD was sparse among persons of all ages, and therefore inconclusive, with one exception. Primary school–age children, mostly boys with ADHD combined type, showed improvements in symptomatic behavior maintained for 12 to 14 months using pharmacological agents, specifically methylphenidate medication management or atomoxetine. Other subgroups, interventions, and long-term outcomes were under-researched. Evidence regarding large-scale patterns of diagnosis and treatment compared with endemic rates of disorder was inconclusive.