Evidence-based pharmacological treatment options for ADHD in children and adolescents
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Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, causing functional impairment. Its prevalence lies at approximately 5% in children and adolescents and at approximately 2.5% in adults. The disorder follows a multifactorial etiology and shows a high heritability. Patients show a high interindividual and intraindividual variability of symptoms, with executive deficits in several cognitive domains. Overall, ADHD is associated with high rates of psychiatric comorbidities, and insufficient treatment is linked to adverse long-term outcomes. Current clinical guidelines recommend an individualized multimodal treatment approach including psychoeducation, pharmacological interventions, and non-pharmacological interventions. Available medications include stimulants (methylphenidate, amphetamines) and non-stimulants (atomoxetine, guanfacine, clonidine). While available pharmacological treatment options for ADHD show relatively large effect sizes (in short-term trials) and overall good tolerability, there is still a need for improvement of current pharmacotherapeutic strategies and for the development of novel medications. This review summarizes available pharmacological treatment options for ADHD in children and adolescents, identifies current issues in research and evidence gaps, and provides an overview of ongoing efforts to develop new medications for the treatment of ADHD in children and adolescents by means of a systematic cross-sectional analysis of the clinical trials registry www.clinicaltrials.gov.
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The effects of clonidine and guanfacine on noradrenergic transmission in the locus coeruleus and prefrontal cortex are postulated to underlie their benefits on cognition and behavior.
“Their effects on noradrenergic transmission in the locus coeruleus and the prefrontal cortex are postulated to underlie their benefits on cognition and behavior [83, 84].”
From Pharmacological treatment in autism: a proposal for guidelines on common co-occurring psychiatric symptoms (2025) · cites this paper as [84]
Approximately 56% of ADHD cases may achieve clinical improvement with stimulants, while 45% of cases achieve so with non-stimulants.
“approximately 56% of ADHD cases may achieve clinical improvement with stimulants, while 45% of cases achieve so with non-stimulants (Mechler et al., 2022; Newcorn et al., 2008).”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Mechler et al., 2022
For individuals who respond poorly to stimulants, nonstimulant alternatives may be considered, including norepinephrine modulators like atomoxetine and certain antidepressants such as bupropion.
“For individuals who respond poorly to stimulants, nonstimulant alternatives may be considered, including norepinephrine modulators like atomoxetine and certain antidepressants such as bupropion. (Mechler, Banaschewski, Hohmann, & Häge, 2022).”
From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Mechler, Banaschewski, Hohmann, & Häge, 2022
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Manter, M. A., Birtwell, K. B., Bath, J., Friedman, N. D. B., Keary, C. J., Neumeyer, A. M., Palumbo, M. L., Thom, R. P., Stonestreet, E., Brooks, H., et al. (2025) · BMC Medicine · doi:10.1186/s12916-024-03814-0 · Cited by 51 · see citing works
“Their effects on noradrenergic transmission in the locus coeruleus and the prefrontal cortex are postulated to underlie their benefits on cognition and behavior [83, 84].”
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“…non-stimulants may improve the top-down guidance of attention, thought and working memory in those with ADHD via direct effects on NET in the prefrontal cortex (Borchert et al., 2019; Bymaster et al., 2002; Lin & Gau, 2015; Mechler et al., 2022; Morón, Brockington, Wise, Rocha, & Hope, 2002).”
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- Authors
- Mechler, K., Banaschewski, T., Hohmann, S., & Häge, A.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Mechler, Konstantin
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 230
- Pages
- 107940
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W3177052253
- Cited by
- 293
- References
- 36
- Citations by year
- 2026: 55 · 2025: 84 · 2024: 86 · 2023: 54 · 2022: 13
- FWCI
- 6.82
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Pharmacology & Therapeutics (publishedVersion, cc-by)
- 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
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
- Keywords
- attention deficit hyperactivity disorder, ADHD medication, children and adolescents, stimulant medication, methylphenidate, amphetamine, non-stimulant medication, atomoxetine, guanfacine, clonidine, psychiatric comorbidity, executive dysfunction, clinical trial registries
- MeSH terms
- Atomoxetine Hydrochloride, Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Cross-Sectional Studies, Humans, Methylphenidate
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