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Cited by 45Attention Deficit Hyperactivity DisorderNeuroethics, Human Enhancement, Biomedical InnovationsPharmacology and Obesity Treatment

Nonstimulant Medications for Attention-Deficit/Hyperactivity Disorder (ADHD) in Adults: Systematic Review and Meta-Analysis

Radonjić, Nevena V., Bellato, Alessio, Khoury, Nayla M., Cortese, Samuele, Faraone, Stephen V.·2023·CNS Drugs
DOI 10.1007/s40263-023-01005-8
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Abstract

Background For some adults with Attention-Deficit/Hyperactivity Disorder (ADHD), nonstimulants need to be considered either as a monotherapy or as an adjunct to stimulants.Objectives The objectives of this systematic review and meta-analysis were to assess the efficacy, acceptability, and tolerability of nonstimulants in adults with ADHD.Methods Data sources, searches, and study selection were based on a previously published network meta-analysis of randomized clinical trials (RCTs) by Cortese at al. (Lancet Psychiatry 5(9):727-738, 2018), which we updated in March 2022. Specifically, we searched PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, OpenGrey, Web of Science Core Collection, ProQuest Dissertations and Theses (UK and Ireland), ProQuest Dissertations and Theses (abstracts and international), and the WHO International Trials Registry Platform, including ClinicalTrials.gov for double-blind RCTs with a placebo arm, lasting at least one week, including adults with a diagnosis of ADHD based on DSM-III, DSM-III-R, DSM-IV(TR), DSM-5 or ICD-9- or 10, and reporting data on efficacy, tolerability (drop-out due to side effects) and acceptability (drop-out due to any cause) of guanfacine, clonidine, or atomoxetine. Additionally, we searched for RCTs of viloxazine extended release (ER), approved for ADHD in 2021. Random-effects meta-analyses were conducted, and the risk of bias for individual RCTs was assessed using the Cochrane Risk of Bias tool.Results We included 18 studies in the meta-analyses (4308 participants) plus one additional study in the narrative synthesis (374 participants). The meta-analysis showed that atomoxetine (15 RCTs) (Hedge's g = - 0.48, 95% CI [- 0.64; - 0.33]), guanfacine (two RCTs) (Hedge's g = - 0.66, 95% CI [- 0.94; - 0.38]) and viloxazine ER (one RCT) were significantly more efficacious than placebo. Atomoxetine was less well tolerated than placebo, while tolerability of guanfacine and viloxazine ER could not be meta-analysed, since only one study, for each medication, reported on it.Conclusions All investigated nonstimulants were more efficacious in the treatment of ADHD in adults, than placebo, while the placebo had better acceptability and tolerability.Protocol https://osf.io/5vnmt/?view_only=2bf87ed12ba94645babedceeee4c0120 .

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Authors
Radonjić, N. V., Bellato, A., Khoury, N. M., Cortese, S., & Faraone, S. V.
Affiliations
  • SUNY Upstate Medical University (US)
  • University of Nottingham (GB)
Corresponding author
Faraone, Stephen V.
ORCID
Venue
CNS Drugs
Publisher
Springer Science and Business Media LLC
Published
2023-05
Volume
37
Issue
5
Pages
381-397
ISSN
  • 1172-7047 (ISSN-L)
  • 1179-1934
DOI
10.1007/s40263-023-01005-8
OpenAlex
W4376132455
Cited by
45
References
40
Citations by year
2026: 14 · 2025: 19 · 2024: 11 · 2020: 1
FWCI
2.00
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • CNS Drugs (publishedVersion)
  • PubMed (publishedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
Funders
  • National Institute of Mental Health (R21MH126494, R01MH116037)
  • National Institute of Neurological Disorders and Stroke (R01NS128535)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (U01AR076092)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neuroethics, Human Enhancement, Biomedical Innovations
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Keywords
adult ADHD, non-stimulant medication, atomoxetine, guanfacine, clonidine, treatment efficacy, tolerability, acceptability, placebo response, adjunctive therapy, risk of bias, adverse events, cost-effectiveness, quality of life, social functioning
MeSH terms
Atomoxetine Hydrochloride, Adult, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Humans, Viloxazine, Randomized Controlled Trials as Topic, Guanfacine

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