SummaryBackgroundThe benefits and safety of medications for attention-deficit hyperactivity disorder (ADHD) remain controversial, and guidelines are inconsistent on which medications are preferred across different age groups. We aimed to estimate the comparative efficacy and tolerability of oral medications for ADHD in children, adolescents, and adults.MethodsWe did a literature search for published and unpublished double-blind randomised controlled trials comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion, clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo. We systematically contacted study authors and drug manufacturers for additional information. Primary outcomes were efficacy (change in severity of ADHD core symptoms based on teachers' and clinicians' ratings) and tolerability (proportion of patients who dropped out of studies because of side-effects) at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios (ORs) and standardised mean differences (SMDs) using pairwise and network meta-analysis with random effects. We assessed the risk of bias of individual studies with the Cochrane risk of bias tool and confidence of estimates with the Grading of Recommendations Assessment, Development, and Evaluation approach for network meta-analyses. This study is registered with PROSPERO, number CRD42014008976.Findings133 double-blind randomised controlled trials (81 in children and adolescents, 51 in adults, and one in both) were included. The analysis of efficacy closest to 12 weeks was based on 10 068 children and adolescents and 8131 adults; the analysis of tolerability was based on 11 018 children and adolescents and 5362 adults. The confidence of estimates varied from high or moderate (for some comparisons) to low or very low (for most indirect comparisons). For ADHD core symptoms rated by clinicians in children and adolescents closest to 12 weeks, all included drugs were superior to placebo (eg, SMD −1·02, 95% CI −1·19 to −0·85 for amphetamines, −0·78, −0·93 to −0·62 for methylphenidate, −0·56, −0·66 to −0·45 for atomoxetine). By contrast, for available comparisons based on teachers' ratings, only methylphenidate (SMD −0·82, 95% CI −1·16 to −0·48) and modafinil (−0·76, −1·15 to −0·37) were more efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD −0·79, 95% CI −0·99 to −0·58), methylphenidate (−0·49, −0·64 to −0·35), bupropion (−0·46, −0·85 to −0·07), and atomoxetine (−0·45, −0·58 to −0·32), but not modafinil (0·16, −0·28 to 0·59), were better than placebo. With respect to tolerability, amphetamines were inferior to placebo in both children and adolescents (odds ratio [OR] 2·30, 95% CI 1·36–3·89) and adults (3·26, 1·54–6·92); guanfacine was inferior to placebo in children and adolescents only (2·64, 1·20–5·81); and atomoxetine (2·33, 1·28–4·25), methylphenidate (2·39, 1·40–4·08), and modafinil (4·01, 1·42–11·33) were less well tolerated than placebo in adults only. In head-to-head comparisons, only diff...

The findings of this study do not support the assumption that adulthood ADHD is necessarily a continuation of childhood ADHD. Rather, they suggest the existence of 2 syndromes that have distinct developmental trajectories.

The present study aimed at identifying the full range of mental disorders comorbid to attention-deficit/hyperactivity disorder (ADHD) in children and adolescents (age 4-17) diagnosed in Danish psychiatric hospitals between 1995 and 2010. A total of 14,825 patients were included in the study and comorbid disorders diagnosed concurrent with ADHD were identified. Associations of comorbid disorders with sex, age, and other mental disorders were investigated by logistic regression analysis. In the total sample, 52.0 % of the patients had at least one psychiatric disorder comorbid to ADHD and 26.2 % had two or more comorbid disorders. The most frequent comorbid disorders were disorders of conduct (16.5 %), specific developmental disorders of language, learning and motor development (15.4 %), autism spectrum disorders (12.4 %), and intellectual disability (7.9 %). Male sex was generally associated with an increased risk for neuropsychiatric disorders while female sex was associated more frequently with internalizing disorders. The analysis of associations between the various comorbid disorders identified several clusters highlighting the differential developmental trajectories seen in patients with ADHD. The study provides evidence that comorbidity with mental disorders is developmentally sensitive. Furthermore, the study shows that particular attention should be given to patients with neurodevelopmental disorders such as autism and intellectual disability in future longitudinal analyses. These disorders are very frequent in patients with ADHD, and the affected patients might follow a different course than patients without these disorders.

The long-term outcome of almost half of all individuals with autistic disorders is poor. The subtype of autism in childhood may be a predictor for specific long-term outcomes, but in general, little is known about the pathways and predictors.

Incidence rates had increased slightly for AN, but were stable for BN across 16 years in this nationwide study and to a large extent were reflective of a general increase in diagnosed mental disorders.