Research Article: The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials

Date Published: July 12, 2017

Publisher: Public Library of Science

Author(s): Ferrán Catalá-López, Brian Hutton, Amparo Núñez-Beltrán, Matthew J. Page, Manuel Ridao, Diego Macías Saint-Gerons, Miguel A. Catalá, Rafael Tabarés-Seisdedos, David Moher, Christian Gluud.


Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents.

We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the best profile of acceptability. Stimulants and non-stimulants seemed well tolerated. Among medications, methylphenidate, amphetamine, atomoxetine, guanfacine and clonidine seemed significantly more efficacious than placebo. Methylphenidate and amphetamine seemed more efficacious than atomoxetine and guanfacine. Methylphenidate and clonidine seemed better accepted than placebo and atomoxetine. Most of the efficacious pharmacological treatments were associated with harms (anorexia, weight loss and insomnia), but an increased risk of serious adverse events was not observed. There is lack of evidence for cognitive training, neurofeedback, antidepressants, antipsychotics, dietary therapy, fatty acids, and other complementary and alternative medicine. Overall findings were limited by the clinical and methodological heterogeneity, small sample sizes of trials, short-term follow-up, and the absence of high-quality evidence; consequently, results should be interpreted with caution.

Clinical differences may exist between the pharmacological and non-pharmacological treatment used for the management of ADHD. Uncertainties about therapies and the balance between benefits, costs and potential harms should be considered before starting treatment. There is an urgent need for high-quality randomised trials of the multiple treatments for ADHD in children and adolescents. PROSPERO, number CRD42014015008.

Partial Text

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in children and adolescents. Recent estimates suggest that ADHD affects about 3–7% of young people worldwide [1–2], producing considerable impact on health services and the community [3–5]. ADHD is a childhood-onset disorder characterized by a persistent pattern of symptoms of developmentally inappropriate and impaired inattention and/or hyperactivity/impulsivity, with difficulties often continuing into adulthood. The diagnosis of the disorder also requires the presence of symptoms across more than one setting (e.g., home and school) and requires that the symptoms needed for diagnosis result in academic, social, or occupational impairment [6–8].

This systematic review was conducted and reported in accordance with the reporting guidance provided in the PRISMA statement extension for systematic reviews incorporating network meta-analysis [29] (S1 Checklist). We developed a systematic review protocol and registered with PROSPERO (CRD42014015008) [30]. Our methods are briefly described here (and explained in more detail in S1 Text and in the published protocol [30]).

ADHD is one of the most commonly diagnosed and treated psychiatric disorders in childhood. In many Western countries, the prescribing rates have increased dramatically, with wide variations in medical practice [53–56] that have led to remarkable controversies and public debate around the clinical (and social) management of ADHD [57–60]. Our analysis of 190 studies that enrolled 26,114 participants randomly assigned to 52 different interventions (grouped in 32 therapeutic classes) has evaluated the comparative effects of multiple pharmacological and non-pharmacological treatments used in children and adolescents with ADHD.




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