Methylphenidate has been used for decades in the treatment of ADHD. There are different hypotheses about how exactly this psychostimulant exerts its effects. One relates to methylphenidate affecting dopaminergic neurotransmission in the nucleus accumbens and associated neuronal networks. To find out more, a research team conducted an imaging study.
Methylphenidate (MPH) is the drug of choice for the treatment of clinically relevant attention deficit hyperactivity disorder (ADHD) [1]. Ritalin® is the brand name of the oldest and most widely used MPH preparation. Other drugs used in Switzerland that also contain the active ingredient MPH are Medikinet MR®, Equasym®, Focalin® and Concerta® [2]. A distinction is made between short- and long-acting preparations. Often a short-acting MPH preparation is used at the beginning of treatment, e.g. the 10 mg Ritalin® tablet. The MPH in this form is rapidly absorbed by the body and begins to take effect after about 30 minutes. After 3-4 hours, the effect quickly wears off. In addition, it is possible to deliver stimulants in a long-acting form. Here, the active ingredient is released from the tablet with a delay, and the effect is maintained for 7 to a maximum of 14 hours, depending on the preparation. However, the data on the duration of action are only guidelines; the therapy can be adapted to the needs of the child as best as possible [3].
MRI examination in crossover design.
Researchers conducted a randomized, placebo-controlled, double-blind crossover study at Fukui University Hospital, Japan [4]. The mean age of the 27 children with ADHD was 10.6 years (SD 1.8; age range: 7.3-15.5 years). Among the 49 control subjects without ADHD, the mean age was 11.1 years (SD 2.3; age range 6.1-15.6 years). The inclusion criteria can be seen in the box. Children with ADHD were scanned twice with resting-state functional magnetic resonance imaging under methylphenidate and placebo conditions. During the first appointment, they were administered MPH (1.0 ± 0.1 mg/kg) or placebo (lactose) with osmotic release (OROS), as in previous studies under double-blind conditions. Five to eight hours after administration, when blood MPH concentrations were maximal, the children underwent a resting-state fMRI examination and performed a standardized continuous performance test outside the MRI scanner. At the second appointment (within 1 to 6 weeks after the first appointment), children with ADHD underwent resting-state fMRI scans and performed the performance test after taking the second medication: children who had taken OROS-MPH at the first appointment received the placebo at the second appointment under double-blind conditions, and vice versa.
The control group, study participants without ADHD, completed the same resting-state fMRI scan once without OROS-MPH or placebo.
Methylphenidate has been shown to modulate neuronal activity
Methylphenidate (MPH) was shown to increase spontaneous neuronal activity in the nucleus accumbens and in salience and default mode (“default mode”) networks [4].
- In the performance test, MPH significantly reduced omission errors, mean reaction time, and intraindividual response variability during a task (IIRV) in the ADHD group (p<0.001 each).
- Methylphenidate-induced modulation of spontaneous neuronal activity in the “default mode” network predicted the treatment effect in terms of intraindividual response variability (IIRV) (r=-0.46, p=0.016).
- Regarding effects of MPH on spontaneous neuronal activity in the nucleus accumbens, the amplitude of low-frequency fluctuations (ALFF) in the right nucleus accumbens was significantly higher in the ADHD-MPH condition than in the ADHD-placebo condition (p<0.05, Bonferroni-corrected, Cohen’s d=0.55).
- ALFF was significantly higher in the salience networks (SN) and in the “default mode” network (DMN) in the ADHD-MPH condition than in the ADHD-placebo condition (SN: p<0.05, Cohen’s d=0.57; DMN: p<0.01, Cohen’s d=0.66; Bonferroni corrected in each case). There was no significant difference in the left and right frontoparietal networks (p>0.05). Multiple linear regression analysis revealed that only MPH modulation of the ALFF similarity pattern within the “default mode” network was significantly associated with drug effects on intraindividual response variability (Table 1) . This indicates that this is a crucial neurobiological mechanism of action.
These findings expand the current understanding of the neurobiological mechanisms underlying MPH treatment in children with ADHD, and according to study authors, clinically useful biomarkers for evaluating treatment success may be derived from them in the future.
Literature:
- Praxis Suchtmedizin Schweiz, www.praxis-suchtmedizin.ch/praxis-suchtmedizin/index.php/de/medikamente/einleitung-mh, (last accessed 10.02.2023)
- Swissmedic: Medicinal Product Information, www.swissmedicinfo.ch,(last accessed 10.02.2023).
- “Medication treatment of children and adolescents with attention deficit hyperactivity disorder ADHD,” March 2022,
www.pukzh.ch/sites/default/assets/File/
Informationen%20Stimulanzien%20und%20Ritalin.pdf, (last accessed 10.02.2023) - Mizuno Y, et al.: Methylphenidate Enhances Spontaneous Fluctuations in Reward and Cognitive Control Networks in Children With Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, available online 23 October 2022, www.sciencedirect.com/science/article/pii/S2451902222002476, (last accessed 10.02.2023)
HAUSARZT PRAXIS 2023; 18(2): 24–25
InFo NEUROLOGIE & PSYCHIATRIE 2023; 21(2): 30–31
