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Effects of Atomoxetine and Methylphenidate on Sleep in Children With ADHD
Abstract
STUDY OBJECTIVES: This study compared the effects of atomoxetine and methylphenidate on the sleep of children with attention-deficit/hyperactivity disorder (ADHD). This study also compared the efficacy of these medications for treating ADHD in these children. DESIGN: Randomized, double-blind, crossover trial. SETTING: Two sleep disorders centers in the United States; 1 in a private-practice setting and 1 in a hospital setting. PATIENTS: 85 children diagnosed with ADHD. INTERVENTIONS: Twice-daily atomoxetine and thrice-daily methylphenidate, each for approximately 7 weeks. MEASUREMENTS AND RESULTS: Relative to baseline, the actigraphy data indicated that methylphenidate increased sleep-onset latency significantly more than did atomoxetine (39.2 vs 12.1 minutes, p < .001). These results were consistent with the polysomnography data. Child diaries indicated that it was easier to get up in the morning, it took less time to fall asleep, and the children slept better with atomoxetine, compared with methylphenidate. Parents reported that it was less difficult getting their children up and getting them ready in the morning and that the children were less irritable, had less difficulty getting ready for bed, and had less difficulty falling asleep with atomoxetine, compared with methylphenidate. There were no significant differences between medications using the main measures of efficacy for ADHD treatment. Atomoxetine was superior on some secondary ADHD treatment-efficacy measures, based on parent reports. The only significant differences in treatment-emergent adverse events were greater incidence of decreased appetite and greater incidence of insomnia with methylphenidate. CONCLUSIONS: Patients receiving twice-daily atomoxetine had shorter sleep-onset latencies, relative to thrice-daily methylphenidate, based on objective actigraphy and polysomnography data. Although both medications decreased nighttime awakenings, the decrease was greater for methylphenidate.
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In the citing paper
“However, a review of scientific studies comparing medicated and unmedicated children describes inconsistent outcomes, both for polysomnographic measures and for parental reports [123].”
From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [123]
In the citing paper
“In a randomized, double-blind, cross-over study comparing the effect of methylphenidate (given thrice daily) and atomoxetine (given twice daily) on the sleep of children with ADHD, methylphenidate increased sleep-onset latency significantly more than did atomoxetine, both considering actigraphic and polysomnographic data [123].”
From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [123]
In the citing paper
“Both medications decreased night-time awakenings, but the decrease was greater for methylphenidate.”
From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [123]
In the citing paper
“Moreover, both childrens’ diaries and parents’ reports indicated a better quality of sleep (in terms of “getting ready in the morning”, “getting ready for bed”, “falling asleep”) with atomoxetine, compared with methylphenidate.”
From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [123]
In the citing paper
“When data on standard deviations were missing, study authors were contacted to provide missing data [18] or it was calculated using the standard error of subgroups or confidence intervals [19-21].”
In the citing paper
“Nine randomized trials comparing methylphenidate and atomoxetine, with a total of 2762 participants were included.”
In the citing paper
“The outcome in three of these trials favoured atomoxetine suggesting that higher doses of atomoxetine administered twice daily may be more effective.”
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Items 201–214 of 214
Gogne, A. (2025) · Springer eBooks · doi:10.1007/978-3-031-86588-6_4
Methylphenidate and the Paradox of Sedation: A Case Report
Yadav, R., & Garg, B. (2025) · Indian Journal of Psychological Medicine · doi:10.1177/02537176251332231
“13,14 The Naranjo Adverse Drug Reaction (ADR) Probability Scale, which is equally reliable to detailed algorithms, had a score of seven in our case, indicating that the drug might be a probable cause of this reaction.”
刘, 泓. (2025) · Advances in Clinical Medicine · doi:10.12677/acm.2025.1592600
den Hollander, B., Rothuizen-Lindenschot, M., Le, H. L., Ramautar, J. R., Müller, A. R., Geertjens, L., Vaz, F. M., van Eeghen, A. M., Cornel, M. C., Jacobs, B., et al. (2025) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2025.109268
Attention deficit hyperactivity disorder: pharmacotherapy in special situations
Zavadenko, N. N. (2025) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202512510159
Effects of Attention-Deficit/Hyperactivity Disorder Medication on Sleep as Assessed by Actigraphy
Uekusa, S., Watanabe, M., Hanai, Y., Hongo, S., Yoshio, T., & Matsuo, K. (2025) · BPB Reports · doi:10.1248/bpbreports.8.6_164
The effects of the noradrenaline reuptake inhibitor atomoxetine on circadian rhythms in mice.
O'Keeffe, S. (2010) · Maynooth University ePrints and eTheses Archive (Maynooth University)
Fang, Y., Wang, Z. J., Zhang, M., & Sun, F. (2026) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2026.102303
YOUNG, J. L., Powell, R. N., Powell, A., Welling, L. L. M., Granata, L., Saal, J., Nash, M., & Corliss, M. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1769333
“…MPH on sleep-related adverse events, particularly for ER MPHs (Faraone et al., 2019), although individual clinical trials show conflicting results depending on specific characteristics of patients and the type of disturbance measured (Stein et al., 2012; Sangal et al., 2006; Sobanski et al., 2008).”
Roy, S., Veronesi, G. F., Mannarini, S., Pirolo, D., Bellato, A., Cortese, S., & Parlatini, V. (2026) · CNS Drugs · doi:10.1007/s40263-026-01323-7
Tripathi, R., Singh, S., Arya, A., & Agarwal, V. (2026) · Indian Journal of Psychological Medicine · doi:10.1177/02537176261472435
Iwanaka, Y., Ikeda, H., Watanabe, T., Ono, T., Watanabe, Y., & Izumizaki, M. (2026) · Sleep and Biological Rhythms · doi:10.1007/s41105-026-00689-x
Sleep and Quality of Life in ADHD
Bekker, E. M., Kooij, J. J. S., & Buitelaar, J. K. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-343-5_28 · Cited by 7
Mapelli, V. (2008) · PharmacoEconomics Italian Research Articles · doi:10.1007/bf03320651
Metadata
- Authors
- Sangal, R. B., Owens, J., Allen, A. J., Sutton, V., Schuh, K., & Kelsey, D.
- Affiliations
- Rhode Island Hospital (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Schuh, Kory
- Venue
- Sleep
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-12
- Volume
- 29
- Issue
- 12
- Pages
- 1573-1585
- ISSN
- 0161-8105 (ISSN-L)
- 1550-9109
- OpenAlex
- W10589707
- Cited by
- 214
- References
- 0
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 13 · 2015: 17 · 2014: 7 · 2013: 12 · 2012: 11
- FWCI
- 10.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- SLEEP (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- atomoxetine, methylphenidate, attention deficit hyperactivity disorder, children, sleep latency, actigraphy, polysomnography, insomnia, nocturnal awakenings, adverse events, appetite loss
- MeSH terms
- Atomoxetine Hydrochloride, Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Dose-Response Relationship, Drug, Double-Blind Method, Electrophysiology, Female, Humans, Male, Methylphenidate, Propylamines, Sleep, REM, Cross-Over Studies, Adrenergic Uptake Inhibitors
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