The broad range of symptoms associated with MDD implicates several brain circuits and regions, and multiple neurotransmitter systems.1 Increasing any one neurotransmitter (serotonin, noradrenaline, or dopamine) is thought to elevate mood, whereas other aspects of depression may be particularly responsive to an individual neurotransmitter.2,3
A treatment that targets a single monoamine system is unlikely to produce remission in all patients because, based on the variety of symptoms observed, it is evident that the pathophysiology of MDD implicates different anomalies of the serotonin, noradrenaline, and dopamine systems.1 In addition, the serotonergic, noradrenergic, and dopaminergic circuits are functionally connected.4 Consequently, a treatment that enhances the activity of one monoamine system may lead to a decrease in the activity of other monoamine systems.1 For example, an increase in serotonergic activity can result in a decrease in noradrenergic and dopaminergic activity.5 The most effective treatments, therefore, will use more than one mechanism to achieve remission, and will balance the activity of the three neurotransmitter systems.1
References:
- Blier P. Rational site-directed pharmacotherapy for major depressive disorder. Int J Neuropsychopharmacol 2014; 17 (7): 997–1008.
- Stahl SM. Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 5th Edition. © Cambridge University Press, 2021.
- Nutt DJ. Relationship of neurotransmitters to the symptoms of major depressive disorder. J Clin Psychiatry 2008; 69 Suppl E1: 4–7.
- Hamon M, Blier P. Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry 2013; 45: 54–63.
- Blier P, El Mansari M. Serotonin and beyond: therapeutics for major depression. Philos Trans R Soc Lond B Biol Sci 2013; 368 (1615): 20120536.
- Nutt DJ, Spriggs M, Erritzoe D. Psychedelics therapeutics: What we know, what we think, and what we need to research. Neurpharmacol 2023; 223: 109257.
