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9 May 2017

Reale L et al. Eur Child Adolesc Psychiatry 2017; 26: 1443-1457

There is a consensus among experts that comorbid psychiatric disorders are common among children and adolescents with ADHD. This multicentre observational study aimed to evaluate the prevalence rate of psychiatric comorbidities and treatment outcomes in treatment-naïve children and adolescents with ADHD.

In June 2011, the Lombardy ADHD registry, an Italian regional registry compiled of data from 18 local ADHD centres which aimed to ensure the appropriate care and safety of drug use in children with ADHD, was set up. This registry aimed to systematically monitor pharmacological treatments and behavioural intervention in children with ADHD, and a strict diagnostic assessment of the disorder prior to treatment was required.* Following a diagnosis of ADHD, follow-up visits at 3 and 6 months, then every 6 months, were scheduled. Data were analysed every month. The current multicentre observational study focussed on data obtained between June 2011 and August 2016, with a 12±3 month follow-up period.

In total, 1919 (67%) participants met the diagnostic criteria for ADHD (1635 males [85%] and 284 females [16%]). Of these, 650 (34%) participants received a diagnosis of ADHD only, and 1269 (66%) a diagnosis of ADHD with ≥1 comorbid psychiatric disorder.

The rate of sleep disorders (23% vs 13%, p≤0.0001) and oppositional defiant disorder (ODD) (20% vs 11%, p<0.0001) were significantly higher in those with ADHD compared with those without ADHD. Risk calculations based on logistic regression models confirmed that ADHD was a significant risk factor for sleep disorders (OR 1.81, 95% CI 1.31–2.51) and ODD (OR 1.93, 95% CI 1.37–2.72). Moreover, no significant difference between observed and calculated values existed. Learning disorders, sleep and anxiety disorders and ODD were the most common psychiatric comorbidities in those with ADHD (all >10% frequency).

Compared with psychological treatments prescribed at time of ADHD diagnosis, decreases in psychological therapies administered for those with and without psychiatric comorbidity were observed (12% vs 20% without comorbidity). ODD was the only comorbid psychiatric disease to show a smaller decrease between rates of treatment prescribed versus received, compared with other common psychiatric comorbidities.

Of the 724 participants evaluated after 1 year of therapy, 141 showed improvement (20%), 241 minimal improvement (33%), 299 no significant improvement (41%) and 43 worsening (6%). Results showed similar rates in patients with ADHD with or without psychiatric comorbidity. A statistical difference between treatment groups was observed in: ADHD with psychiatric comorbidities (p<0.001), with learning difficulties (p=0.004), with ODD (p=0.019) and the total ADHD group (p<0.001). Results indicated that combined treatment offered superiority over pharmacology treatment alone. After stratifying for CGI-S at baseline evaluation, no differences were observed in improvement rates for all groups (CGI-S <5 versus ≥5, p>0.05).

A medium effect size (ES) was observed for participants receiving methylphenidate treatment alone with ADHD only (0.63), and a large ES was observed for participants with ADHD with psychiatric comorbidity (0.89). A large and significant ES was observed with combined treatment for ADHD with psychiatric comorbidity (0.75).

As this was not a randomised clinical trial, and the existence of service organisation variables may have introduced bias into treatment efficacy evaluations, limitations within this study exist.

The authors conclude that ADHD is a multifactorial disorder with a high rate of psychiatric comorbidity in children and adolescents with ADHD, and that, in order to ensure the most appropriate management strategies are in place, diagnostic, therapeutic and organisational services require expansion.

Read more about comorbidity prevalence rates in children and adolescents with ADHD here


CGI-S, clinical global impressions-severity scale; CI, confidence interval; OR, odds ratio
*Diagnostic assessment of the disorder included: 1) a clinical anamnestic and psychiatric interview; 2) a neurological examination; 3) cognitive evaluation by Wechsler Scales; 4) a psychopathology overview and comorbidity assessment by the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS); 5) the Child Behaviour Checklist (CBCL) and/or the Conners’ Parent Rating Scale-Revised (CPRS-R) rated by parents; 6) the Conners’ Teacher Rating Scale-Revised (CTRS‑R); 7) the Clinical Global Impressions-Severity Scale (CGI-S).
Participants receiving methylphenidate were also monitored 1-week and 1-month following ADHD diagnosis, and those receiving atomoxetine, 1-month following ADHD diagnosis.
An effect size of 0.2 is regarded as small, 0.5 as medium and 0.8 as large.

Reale L, Bartoli B, Cartabia M, et al. Comorbidity prevalence and treatment outcome in children and adolescents with ADHD. Eur Child Adolesc Psychiatry 2017; 26: 1443-1457.

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