A Focus on Agomelatine – Mechanism of Action and Efficacy
Agomelatine is a novel and atypical antidepressant that acts as a melatonergic antidepressant and has a distinctly favourable side effect profile.
The majority of antidepressant research for the past three decades has focused on increasing monoamine levels in the synaptic cleft.
This can be achieved either by blocking reuptake, or blocking the breakdown, of synaptic monoamines. It is believed that monoamine-based antidepressants initiate adaptive neuronal changes through binding to monoamine receptors and/or monoamine transporters.
Popular first-choice monoamine-based antidepressant drugs include selective serotonin reuptake inhibitors (SSRIs) and serotonin–noradrenaline reuptake inhibitors (SNRIs). These agents have replaced tricyclic antidepressant (TCA) drugs because of their improved efficacy and more favourable adverse-effect profile.
However, SSRI and SNRI drugs only have modest efficacy with response rates reported at approximately 50% .
These drugs are also associated with common treatment-emergent adverse events including nausea, sexual dysfunction, weight gain, and insomnia all of which limits tolerability.
Taylor D et al., The Maudsley Prescribing Guidelines in Psychiatry (12th Edition). Wiley Blackwell. 2015
Arango C, Buitelaar JK, Fegert JM, Olivier V, Pénélaud PF, Marx U, Chimits D, Falissard B; study investigators. Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomised, controlled, phase 3 trial in nine countries. Lancet Psychiatry. 2021