Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis

• Published in: PloS one Vol. 15; no. 10; p. e0240584
• Main Authors: Elliott, Jesse, Johnston, Amy, Husereau, Don, Kelly, Shannon E, Eagles, Caroline, Charach, Alice, Hsieh, Shu-Ching, Bai, Zemin, Hossain, Alomgir, Skidmore, Becky, Tsakonas, Eva, Chojecki, Dagmara, Mamdani, Muhammad, Wells, George A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.10.2020; Public Library of Science (PLoS)
• Subjects: Adult; Adults; Amphetamine - adverse effects; Amphetamine - therapeutic use; Amphetamines; Atomoxetine Hydrochloride - adverse effects; Atomoxetine Hydrochloride - therapeutic use; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - epidemiology; Attention Deficit Disorder with Hyperactivity - pathology; Attention deficit hyperactivity disorder; Bayes Theorem; Bayesian analysis; Bias; Biology and Life Sciences; Bupropion; Bupropion - adverse effects; Bupropion - therapeutic use; Central Nervous System Stimulants - adverse effects; Clinical decision making; Clinical trials; Computer and Information Sciences; Decision making; Dextroamphetamine - adverse effects; Dextroamphetamine - therapeutic use; Drug therapy; Drug-Related Side Effects and Adverse Reactions - classification; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Emergency medical care; Emergency medical services; Executive function; Female; Guanfacine - adverse effects; Guanfacine - therapeutic use; Health risks; Humans; Intervention; Lisdexamfetamine Dimesylate - adverse effects; Lisdexamfetamine Dimesylate - therapeutic use; Long-term effects; Male; Medicine and Health Sciences; Meta-analysis; Methylphenidate; Methylphenidate - adverse effects; Methylphenidate - therapeutic use; Modafinil; Modafinil - adverse effects; Modafinil - therapeutic use; Network Meta-Analysis; Patient outcomes; Patients; Pharmacology; Physical Sciences; Quality of Life; Randomized Controlled Trials as Topic; Research and Analysis Methods; Risk analysis; Risk assessment; Salts; Canada; Toronto Ontario Canada; Ottawa Ontario Canada
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0240584

Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD. We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework. Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, 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. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration. Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs. PROSPERO no. CRD 42015026049.