Nonstimulant Treatments for ADHD
Open accessAbstract
Nonstimulants have an important role when response or tolerability to psychostimulants is poor, when certain comorbid disorders are present, or if patients prefer nonstimulants. Here, we discuss monotherapy and combined treatment of ADHD and review mechanism of action, pharmacokinetics, efficacy, tolerability, and safety of approved, off-label, and pipeline nonstimulants. We present detailed information regarding the 4 FDA-approved nonstimulant medications-the norepinephrine reuptake inhibitors, atomoxetine and viloxazine extended release, and the α-2 adrenergic agonists, clonidine XR and guanfacine XR. We additionally review evidence regarding the off-label use of a variety of other medications. Variability across and within drug classes in nature of response, approach to titration, and temporal characteristics of treatment allow a nuanced treatment approach for individuals with comorbid disorders and complicated clinical presentations. Availability of nonstimulant medications enhances our opportunity to offer personalized treatment of ADHD across the lifespan.
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The neuropharmacological pathways of nonstimulants are notably diverse, yet they all converge on targeting the norepinephrine transporter in some capacity for the treatment of ADHD.
“the neuropharmacological pathways of nonstimulants are notably diverse, yet they all converge on targeting the norepinephrine transporter in some capacity for the treatment of ADHD”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Newcorn, Krone, & Dittmann, 2022
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References 67 · Cited by 29
- Authors
- Newcorn, J. H., Krone, B., & Dittmann, R. W.
- Affiliations
- Mount Sinai Health System (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Newcorn, Jeffrey H.
- Venue
- Child and Adolescent Psychiatric Clinics of North America
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 31
- Issue
- 3
- Pages
- 417-435
- ISSN
- 1056-4993 (ISSN-L)
- OpenAlex
- W4280586647
- Cited by
- 29
- References
- 67
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 4
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 344 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Child and Adolescent Psychiatric Clinics of North America (acceptedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- attention deficit hyperactivity disorder, non-stimulant medication, atomoxetine, viloxazine, clonidine, guanfacine, norepinephrine reuptake inhibitors, alpha-2 adrenergic agonists, off-label drug use, comorbidities, pharmacokinetics, drug tolerability, treatment titration, personalized treatment
- MeSH terms
- Atomoxetine Hydrochloride, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Clonidine, Humans, Guanfacine, Adrenergic alpha-2 Receptor Agonists
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