Agomelatine for ADHD
The trade name of agomelatine is Valdoxan.
Effect:
- Agonistic on melatonin MT1 receptor
- Agonistic on melatonin MT2 receptor
- Blockade of the serotonin 5HT-2-B receptor in the suprachiasmatic nucleus1
- Blockade of the serotonin 5HT-2-C receptor in the suprachiasmatic nucleus1
- Is designed to increase the expression of the cytoskeleton-associated protein (ARC) in the PFC2
- Should lead to an optimization of learning, consolidation of long-term memory and improved survival of neurons
- Modulation of glutamatergic neurotransmission in regions associated with mood and cognition2
Agomelatine moderates the synchronization of circadian rhythms.342 It is therefore particularly worth considering if the sleep rhythm is shifted backwards (which is common in people with ADHD).
70 to 80 % of all children with ADHD have sleep disorders.
In adults with ADHD, the figure is probably between 20 and 30%.
Sleep is an eminently effective therapeutic agent for ADHD, as for all other disorders of the stress regulation system. One hour more sleep at night reduces the cortisol level in the morning by 21%.
It is possible that agomelatonin not only has a sleep-promoting and antidepressant effect, but also has an independent effect on ADHD: the effectiveness of agomelatonin was compared with that of methylphenidate in a randomized double-blind study with n = 54 children. Both medications performed comparably in the parents’ and teachers’ assessment of the children. Naturally, the children treated with agomelatine had fewer sleep disorders.5 Agomelatine has barely been researched as an ADHD medication.
- Agomelatine causes a 5HT2C receptor blockade, which indirectly causes an increase in noradrenaline and dopamine in the frontal cortex.1
- However, agomelatine does not increase the dopamine level in the nucleus accumbens and the striatum,1 where the dopamine deficit in ADHD causes the problems with drive and motivation as well as with attention regulated by motivation.
- The noradrenaline level in the frontal cortex is increased in a dose-dependent manner, with adrenergic activity in the nucleus coeruleus increasing at the same time.1
MPH and amphetamine drugs, on the other hand, have a dopamine-increasing effect on the PFC and striatum.
Agomelatine is metabolized by:6
- Cytochrome P450 1A2 (CYP1A2) (90 %)
- CYP2C9/2C19 (10%)
For agomelatine as a sleep aid, see also ⇒ sleeping pills / sleep medication suitable for ADHD In the article ⇒ Sleep problems with ADHD.
Millan, Gobert, Lejeune, Dekeyne, Newman-Tancredi, Pasteau, Rivet, Cussac (2003): The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways; J Pharmacol Exp Ther. 2003 Sep;306(3):954-64. ↥ ↥ ↥ ↥ ↥
Savino R, Polito AN, Marsala G, Ventriglio A, Di Salvatore M, De Stefano MI, Valenzano A, Marinaccio L, Bellomo A, Cibelli G, Monda M, Monda V, Messina A, Polito R, Carotenuto M, Messina G (2023): Agomelatine: A Potential Multitarget Compound for Neurodevelopmental Disorders. Brain Sci. 2023 Apr 27;13(5):734. doi: 10.3390/brainsci13050734. PMID: 37239206; PMCID: PMC10216109. REVIEW ↥ ↥ ↥
Redman, Francis (2009): Entrainment of Rat Circadian Rhythms by the Melatonin Agonist S-20098 Requires Intact Suprachiasmatic Nuclei But Not the Pineal ↥
Strat, Gorwood (2008): Agomelatine, an innovative pharmacological response to unmet needs; J Psychopharmacol. 2008 Sep;22(7 Suppl):4-8. doi: 10.1177/0269881108092593 ↥
Salardini, Zeinoddini, Kohi, Mohammadi, Mohammadinejad, Khiabany, Shahriari, Akhondzadeh (2016): Agomelatine as a Treatment for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Double-Blind, Randomized Clinical Trial. J Child Adolesc Psychopharmacol. 2016 Jun 10. ↥