Nonstimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adults: systematic review and meta-analysis
Nonstimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adults: systematic review and meta-analysis
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
381-397
Radonjic, Nevena V.
8a8b16ac-80c8-485b-b69d-bac424d24066
Bellato, Alessio
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Khoury, Nayla M.
7f3cccc6-2eff-445a-a998-ceffddaaed87
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Faraone, Stephen V.
51b0ac60-c850-49bd-a213-a47f01673e50
11 May 2023
Radonjic, Nevena V.
8a8b16ac-80c8-485b-b69d-bac424d24066
Bellato, Alessio
0ee4c34f-3850-4883-8b82-5717b74990f7
Khoury, Nayla M.
7f3cccc6-2eff-445a-a998-ceffddaaed87
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Faraone, Stephen V.
51b0ac60-c850-49bd-a213-a47f01673e50
Radonjic, Nevena V., Bellato, Alessio, Khoury, Nayla M., Cortese, Samuele and Faraone, Stephen V.
(2023)
Nonstimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adults: systematic review and meta-analysis.
CNS drugs, 37 (5), .
(doi:10.1007/s40263-023-01005-8).
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
Text
Manuscript revision 02272023
- Accepted Manuscript
Available under License Other.
More information
Accepted/In Press date: 11 April 2023
e-pub ahead of print date: 11 May 2023
Published date: 11 May 2023
Additional Information:
Funding Information:
Dr. Radonjić is supported by the European Union’s Horizon 2020 research and innovation Commission under Grant agreement no 945151 and Patrick Lee Foundation. Dr. Faraone is supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement no 965381; NIMH Grants U01AR076092-01A1, 1R21MH1264940, R01MH116037; 1R01NS128535–01; Oregon Health and Science University, Otsuka Pharmaceuticals, Noven Pharmaceuticals Incorporated, and Supernus Pharmaceutical Company. Drs. Bellato, Cortese, and Khoury have declared that they have no funding to disclose.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Identifiers
Local EPrints ID: 477815
URI: http://eprints.soton.ac.uk/id/eprint/477815
ISSN: 1172-7047
PURE UUID: ba8ab104-6ef5-4996-9208-5d4802980fd5
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Date deposited: 15 Jun 2023 16:31
Last modified: 11 Apr 2024 04:01
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Contributors
Author:
Nevena V. Radonjic
Author:
Alessio Bellato
Author:
Nayla M. Khoury
Author:
Stephen V. Faraone
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