Few differences were observed between individual pharmacotherapies for the treatment of adults with attention-deficit hyperactivity disorder (ADHD), according to the findings of a recently published systematic review and network meta-analysis.

Given the lack of head-to-head trials directly comparing the multiple treatment options available to manage adult ADHD, the authors aimed to evaluate the relative effects of individual therapies. Clinical response was the primary end point of the review while secondary outcomes included quality of life, executive function, driving behavior, study withdrawal due to adverse events, discontinuation of treatment, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits.

Pair-wise meta-analyses and Bayesian network meta-analyses were used to pool data. Additionally, Cochrane’s Risk of Bias tool was used to assess the risk of bias while the GRADE framework was used to evaluate the certainty of the evidence.

The review included a total of 81 unique trials that reported 1 or more outcomes of interest. It was noted that the majority of included trials were “at high or unclear risk of at least 1 important source of bias,” with only 5 RCTs having an overall low risk of bias. Pharmacotherapies assessed in the included trials were methylphenidate, atomoxetinedextroamphetaminelisdexamfetamineguanfacine, bupropion, mixed amphetamine salts, and modafinil.

“As a class, ADHD pharmacotherapy improved patient and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low,” the study authors reported. Additionally, only a small number of differences were observed between individual medications; atomoxetine was found to be associated with improved patient-reported clinical response as well as quality of life when compared with placebo.

Findings of the analysis also revealed no significant differences between ADHD pharmacotherapies and placebo when assessing the risk of adverse events or discontinuation of treatment. It was found, however, that a significantly higher proportion of patients in the ADHD pharmacotherapy group withdrew from the study due to adverse events compared with patients who received placebo. The authors also noted that there was a limited number of RCTs that reported on the incidence of adverse events over a long treatment period.

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“Overall, the certainty of the evidence was very low to low across outcomes, and additional long-term high-quality RCTs are needed to inform on patient-important outcomes such as quality of life and adverse events over a long treatment duration,” the authors concluded.  They added that in the absence of data, treatment selection should be based on patient specific factors as well as the potential risks and benefits of the drug.

Disclosure: Multiple authors declared conflicts of interest. Please refer to the original article for a full list of disclosures.


1.      Elliott J, Johnston A, Husereau D, et al. Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis [published online October 21, 2020]. PLoS ONE. doi: 10.1371/journal.pone.0240584