Revisão sistemática do tratamento farmacológico de pacientes com transtorno do déficit de atenção com hiperatividade associado ao transtorno de ansiedade

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is defined as a persistent condition of inattention and/or hyperactivity/impulsivity which promotes interference in the development of the subject. It is estimated that between 65 and 89% of adult ADHD patients suffer from one or more life-long psychiatric disorders. This high percentage of comorbidities is also similar in the child population, where ADHD may be associated with other disorders in 60-100% of cases. One of the often associated disorders is anxiety, which reaches rates close to 25% in many samples of patients with ADHD. Therapies considered first-line for the treatment of ADHD and for Anxiety Disorder (ANX) alone are relatively well established through use of stimulants and cognitive-behavioral therapy, respectively. However, evidence for the most appropriate treatment when both disorders are present is quite controversial. Objectives: Perform systematic review about pharmacological options used to treat ADHD associated with ANX in order to generate evidence about the most effective, safe and tolerable therapeutic option. Methods: Systematic review was performed following the methodological standards recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) in the PubMed, Scopus and Directory of Open Access Journals databases in August 2016 and by manual search. Randomized, double-blind, parallel-design trials evaluating efficacy, safety and/or tolerability outcomes were considered. The methodological quality and risk of bias of included studies were assessed using the Jadad Scale and the Cochrane Collaboration tool. Relevant data from all included studies were collected using a previously developed form. At this stage, pertinent information from each study, according to the objective of the study, was extracted and analyzed. Results: A total of 1590 articles were found from databases searched, 218 were evaluated in full text for eligibility and finally 5 studies met all inclusion criteria and were included in the systematic review. Two of the included studies used atomoxetine compared to placebo, in which one population was composed of adult patients and the other was pediatric. Desipramine was also one of the medications used, which was studied to treat children from 6 to 17 years old. The others two studies included methylphenidate as pharmacological treatment for pediatric patients, but in one of them fluvoxamine was combined with methylphenidate. Regarding the methodological quality, studies obtained scores of 3, 4 and 5 on the Jadad scale, being considered of moderate to high quality, respectively. The bias risk analysis found that 60% of the articles were supported by the pharmaceutical industry and therefore classified as having a high bias risk in the "Other bias" domain. All studies in the domains "Blinding of participants and professionals" and "Blinding of outcome assessors" presented low risk of bias. Regarding the domain "Incomplete outcomes", 80% obtained low and 20% high risk of bias. The "Random Sequence Generation", "Allocation Concealment" and "Selective outcome reporting" obtained the following proportions of low vs uncertain risk of bias: 60% vs 40%, 20% vs 80% and 60% vs 40%. Due to the high heterogeneity of eligible studies, it was not possible to combine the results for generation of meta-analyzes. This was mainly due to the diversity of drugs studied and the disparity between the outcomes measures employed. Conclusion: Although few studies have been found, the results obtained through this systematic review point to a more expressive benefit of atomoxetine in the treatment of ADHD with ANX, because it was studied in a wider age group and the studies evaluated atomoxetine through more specific scales for both disorders. It is not possible to say that atomoxetine is superior to the other pharmacological options and only larger clinical trials and with sufficiently fed populations will be able to answer this question.