Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD
Abstract
Unlabelled The neuroendocrine mediators that may contribute to ADHD (Attention deficit and hyperactivity disorder), serotonin and melatonin, are both thought to regulate circadian rhythms, neurological function and stress response. The objective of this study was to determine the effect of the chronic administration of prolonged release methylphenidate (PRMPH) on daily variations in blood serotonin and melatonin and on the excretion of 6-sulphatoxy-melatonin. A total of 179 children (136 males, 42 females) between the ages of 5 and 14 (9.70 ± 2.55) years were enrolled in a controlled quasi-experimental open clinical study. Of the sample, there were 136 Children with ADHD (based on DSM-IV-TR criteria), who were further grouped into subtypes, and the 42 siblings of the participants who did not ADHD patients. Blood samples were taken at 20:00 and 09:00; urine was collected between 21:00 and 09:00. In the ADHD group, the study protocol was repeated after 4.61 ± 2.3 months of treatment. Measurements included melatonin and serotonin by RIA and urine 6-S-aMT by ELISA. Factorial analyses were conducted by STATA 12.0.Results ADHD patients showed reduced morning serotonin with a daily profile that was different than the control group due to the predominance of nocturnal concentrations. PRMPH did not result in any significant changes. Melatonin and its daily profile did not differ between controls and the ADHD group with a diurnal rhythm showing higher morning levels that disappear after PRMPH administration. Melatonin was higher in children with predominantly hyperactive-impulsive/conduct disorder subtype. PRMPH resulted in a decrease in 6-S-aMT excretion for both ADHD subtypes.Conclusion Chronic treatment with prolonged release methylphenidate induces subtle changes in the daily fluctuations and concentrations of both serotonin and melatonin. Improvement in Children's Depression Inventory (CDI) scores was not related to a morning increase in serotonin.
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Healthy children have higher 5-HT concentrations in the morning compared with patients with ADHD, with very similar concentrations in the evening.
“Healthy children have higher 5-HT concentrations in the morning compared with patients with ADHD, with very similar concentrations in the evening [212].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [212]
MPH treatment induced a decrease of 5-HT levels in the evening (without changes in the morning); the effect of MPH on melatonin concentrations was a decrease in the morning and an increase in the evening, normalizing these values to those observed in the non-ADHD population.
“In that study, MPH treatment induced a decrease of 5-HT levels in the evening (without changes in the morning); the effect of MPH on melatonin concentrations was a decrease in the morning and an increase in the evening, normalizing these values to those observed in the non-ADHD population [212].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [212]
The mechanisms of action of MPH involved in the circadian rhythm are unknown, although it has been shown that the use of MPH in children with ADHD normalizes serotonin and melatonin levels to those of non-ADHD population.
“In this regard, the mechanisms of action of MPH involved in the circadian rhythm are unknown, although it has been shown that the use of MPH in children with ADHD normalizes serotonin and melatonin levels to those of non-ADHD population.”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [212]
In 226 children with ADHD, treatment with methylphenidate ablates morning/evening differences in melatonin levels.
“Molina-Carballo et al. (2013) report that in 226 children with ADHD treatment with methylphenidate ablates morning/evening differences in melatonin levels, possibly through raising morning levels of melatonin.”
From A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder (2017) · cites this paper as Molina-Carballo et al. (2013)
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References 58 · Cited by 43
- Authors
- Molina-Carballo, A., Naranjo-Gómez, A., Uberos, J., Justicia-Martínez, F., Ruiz-Ramos, M.-J., Cubero-Millán, I., Contreras-Chova, F., Augustin-Morales, M.-D.-C., Khaldy-Belkadi, H., & Muñoz-Hoyos, A.
- Affiliations
- Complejo Hospitalario Universitario de Granada (ES)
- ORCID
- Uberos, José
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 47
- Issue
- 3
- Pages
- 377-383
- ISSN
- 0022-3956 (ISSN-L)
- OpenAlex
- W2128711810
- Cited by
- 43
- References
- 58
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 7 · 2015: 2 · 2014: 4 · 2013: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- methylphenidate, attention deficit hyperactivity disorder, serotonin, melatonin, circadian rhythm, diurnal variation, children, ADHD subtypes, neuroendocrine regulation, Children's Depression Inventory
- MeSH terms
- Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Body Height, Body Weight, Child, Child, Preschool, Circadian Rhythm, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Melatonin, Methylphenidate, Psychiatric Status Rating Scales, Radioimmunoassay, Retrospective Studies, Serotonin, Body Mass Index
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