A review of Cochrane reviews on pharmacological treatment for attention deficit hyperactivity disorder

Santos, Giovanna Marcílio; Santos, Elaine Marcílio; Mendes, Gustavo Duarte; Fragoso, Yara Dadalti; Souza, Mariani Rafaela; Martimbianco, Ana Luiza Cabrera

doi:10.1590/1980-57642021dn15-040001

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Dementia & Neuropsychologia

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Sumário

Original Article • Dement. neuropsychol. 15 (04) • Oct-Dec 2021 • https://doi.org/10.1590/1980-57642021dn15-040001 copy

A review of Cochrane reviews on pharmacological treatment for attention deficit hyperactivity disorder

Revisão de revisões Cochrane sobre o tratamento farmacológico para transtorno do déficit de atenção e hiperatividade

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT.

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent childhood psychiatric problems.

Objective:

The objective of this study was to identify, synthesize the results, and critically evaluate all Cochrane systematic reviews (SRs) on the pharmacological interventions for children and adolescents (up to age 18) diagnosed with ADHD.

Methods:

The search was performed in the Cochrane Database of Systematic Reviews (via Wiley) in July 2020.

Results:

The search strategy resulted in four SRs of high methodological quality, analyzing 51 randomized clinical trials (9,013 participants). Compared to placebo, treatment with tricyclic antidepressants (TCAs) (desipramine), amphetamine, and methylphenidate showed improvement in symptoms such as difficulty concentrating, impulsivity, and hyperactivity in the short term (up to 6 months). There was an increase in the occurrence of adverse events, such as reduced appetite, difficulty sleeping, and abdominal pain. Insufficient evidence was found to support the effects of supplementation with polyunsaturated fatty acids.

Conclusions:

The use of TCAs, amphetamine, and methylphenidate in children and adolescents with ADHD seems to present positive effects and higher rates of minor adverse events when compared to placebo.

Keywords:
attention deficit hyperactivity disorder; systematic review; desipramine; amphetamine; methylphenidate

Methylphenidate versus placebo
Symptom improvement (evaluated by teachers)	Improvement in favor of methylphenidate (SMD −0.77; 95%CI −0.90 to −0.64; 19 RCTs; 1,698 participants)
Overall behavior improvement (evaluated by teachers)	Improvement in favor of methylphenidate (SMD −0.87, 95%CI −1.04 to −0.71; 5 RCTs; 668 participants)
Improvement in quality of life (assessed by parents)	Improvement in favor of methylphenidate(SMD 0.61, 95%CI 0.42–0.80; 3 RCTs; 514 participants)
Serious adverse events (mortality, hospitalization)	No difference between groups, but there was a wide CI (RR 0.98, 95%CI 0.44–2.22; 9 RCTs; 1,532 participants)
Mild adverse events	29% increased risk of adverse events in the methylphenidate group (RR 1.29, 95%CI 1.10–1.51; 21 RCTs; 3,132 participants)
Difficulty sleeping	60% increased risk in methylphenidate group (RR 1.60, 95%CI 1.15–2.23; 13 RCTs; 2,416 participants)
Reduced appetite	266% increased risk methylphenidate group (RR 3.66, 95%CI 2.56–5.23; 16 RCTs; 2,962 participants)

Amphetamine versus placebo
Symptom improvement (assessed by parents)	Improvement in favor of amphetamine (SMD −0.57; 95%CI −0.86 to −0.27; 7 RCTs; 1,247 participants)
Symptom improvement (assessed by teachers)	Improvement in favor of amphetamine(SMD −0.55; 95%CI −0.83 to −0.27; 5 RCTs; 745 participants)
Symptom improvement (assessed by clinicians)	Improvement in favor of amphetamine (SMD −0.84; 95%CI −1.32 to −0.36; 3 RCTs; 813 participants)
Mild adverse events (at least one adverse event)	30% increased risk of adverse events in the amphetamine group (RR 1.30; 95%CI 1.18–1.44; 6 RCTs; 1,742 participants)
Difficulty sleeping	280% increased risk of adverse events in the amphetamine group (imprecise effect – wide CI) (RR 3.80; 95%CI 2.12 to 6.83; 10 RCTs; 2,429 participants)
Reduced appetite	531% increased risk of adverse events in the amphetamine group (imprecise effect – wide CI)(RR 6.31; 95%CI 2.58–15.46; 11 RCTs; 2,467 participants)
Abdominal pain	44% increased risk of adverse events in the amphetamine group (imprecise effect – wide CI) (RR 1.44; 95%CI 1.03–2.00; 10 RCTs; 2,155 participants)

Desipramine versus placebo
Symptom improvement (assessed by parents)	Improvement in favor of desipramine(SMD −1.42; 95%CI −1.99 to −0.85; 2 RCTs; 99 participants)
Symptom improvement (assessed by teachers)	Improvement in favor of desipramine (SMD −0.97; 95%CI −1.66 to −0.28; 2 RCTs; 89 participants)
Symptom improvement (assessed by clinicians)	Improvement seems to be in favor of desipramine, but these results are imprecise (wide CI) (OR 26.41; 95%CI 7.41–94.18; 2 RCTs; 103 participants)
Treatment interruption	No difference between groups, but there was a wide CI and substantial heterogeneity (I²2. Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164(6):942-8. https://doi.org/10.1176/ajp.2007.164.6.942. https://doi.org/https://doi.org/10.1176/... =66%)(RD −0.10; 95%CI −0.25 to 0.04; 3 RCTs; 134 participants)

Nortriptyline versus placebo
Symptom improvement (assessed by clinicians)	Improvement seems to be in favor of desipramine, but these results are imprecise (wide CI) (RR 7.88; 95%CI 1.10–56.12; 1 RCT; 22 participants)

Desipramine versus clonidine (in patients with ADHD plus Tourette’s syndrome)
Symptom improvement (assessed by parents)	Improvement in favor of desipramine (SMD −0.90, 95%CI −1.40 to −0.40; 1 RCT; 68 participants)

Omega-3 plus omega-6 versus placebo
Symptom improvement (reported by the patient)	Improvement seems to be in favor of omega-3/6, but these results are imprecise (wide CI)(RR 2.19; 95%CI 1.04 to 4.62; 2 RCTs; 97 participants)
Symptom improvement (reported by parents)	No difference between groups (SMD −0.17; 95%CI −0.38 to 0.03; 5 RCTs; 413 participants)
Symptom improvement (reported by teachers)	No difference between groups (SMD 0.05; 95%CI −0.18 to 0.27; 4 RCTs; 324 participants)
Quality of life	No difference between groups (MD −0.12; 95%CI -3.71 to 3.47; 1 RCT, 138 participants)
Follow-up losses	No difference between groups (RR 0.95; 95%CI 0.69 to 1.31; 7 RCTs, 589 participants)

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E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br

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[1] Ana Luiza Cabrera Martimbianco. Avenida Conselheiro Nébias, 536 – Encruzilhada – 11045-002 Santos SP – Brazil. E-mail: analuizacabrera@hotmail.com.