Advances in Pharmacological Treatments for Depression: Exploring Novel Developments and Targets – 2023 Update
In the realm of depression treatment, current pharmacological approaches have largely relied on the monoamine deficiency hypothesis, leading to the development of monoamine oxidase inhibitors (MAOIs), tricyclic antidepressant agents (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs) and newer antidepressants such as vortioxetine and agomelatine that indirectly increase monoaminergic transmission through receptor modulation.
Depression is a complex disease, is challenging to diagnose, has an aetiology that is not fully established and can co-exist with several other mental disorders and somatic illnesses. [Gaebel et al. 2017]
However, despite their widespread use, existing treatments suffer significant drawbacks, including delayed onset of efficacy, treatment resistance, and tolerance issues. Moreover, the intricate relationship between depression and somatic illnesses adds complexity to the already intricate polypharmacy regimens.
This article aims to shed light on recent developments in the field, exploring promising receptor targets for the pharmacological treatment of depression.
With the emergence of novel compounds and the advancement of mechanistic knowledge, there is hope for second or third-generation analogues that exhibit enhanced efficacy and improved safety profiles. These advancements can potentially address the urgent need for enhanced depression treatments, particularly for individuals with difficult-to-treat depression.
We do not cover psychedelics in this review as we have covered the mechanism of action of psychedelics in detail in this article.
- Monoamine Oxidase Inhibitors (MAOI) – Mechanism of Action | Psychopharmacology | Clinical Application
- Revisiting Tricyclic Antidepressants: Understanding the Differences and Advantages for Effective Depression Treatment
- Latest Update on the Mechanism of Action of Selective Serotonin Reuptake Inhibitors (SSRIs)
- A Focus on Vortioxetine – Psychopharmacology | Mechanism of Action | Clinical Application
- A Focus on Agomelatine – Mechanism of Action and Efficacy
- Simplified Guide to 21 Common Antidepressants – Mechanisms of Action, Side Effects and Indications
Nettis MA, Lombardo G, Hastings C, Zajkowska Z, Mariani N, Nikkheslat N, Worrell C, Enache D, McLaughlin A, Kose M, Sforzini L, Bogdanova A, Cleare A, Young AH, Pariante CM, Mondelli V. Augmentation therapy with minocycline in treatment-resistant depression patients with low-grade peripheral inflammation: results from a double-blind randomised clinical trial. Neuropsychopharmacology. 2021 Apr;46(5):939-948.
Bai S, Guo W, Feng Y, Deng H, Li G, Nie H, Guo G, Yu H, Ma Y, Wang J, Chen S, Jing J, Yang J, Tang Y, Tang Z. Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. 2020 Jan;91(1):21-32
Bekhbat, M., Li, Z., Mehta, N. D., Treadway, M. T., Lucido, M. J., Woolwine, B. J., … & Felger, J. C. (2022). Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study. Molecular Psychiatry, 27(10), 4113-4121.
Köhler, C. A., Freitas, T. H., Stubbs, B., Maes, M., Solmi, M., Veronese, N., de Andrade, N. Q., Morris, G., Fernandes, B. S., Brunoni, A. R., Herrmann, N., Raison, C. L., Miller, B. J., Lanctôt, K. L., & Carvalho, A. F. (2018). Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis. Molecular neurobiology, 55(5), 4195–4206.
Uher, R., Tansey, K. E., Dew, T., Maier, W., Mors, O., Hauser, J., Dernovsek, M. Z., Henigsberg, N., Souery, D., Farmer, A., & McGuffin, P. (2014). An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. The American journal of psychiatry, 171(12), 1278–1286.
Barroca N.C.B., Baes C.V.W., Martins-Monteverde C.M.S., Bosaipo N.B., Santos da Silva Umeoka M., Tejada J., Antunes-Rodrigues J., de Castro M., Juruena M.F., Garcia-Cairasco N., et al. Evaluation of the HPA Axis’ Response to Pharmacological Challenges in Experimental and Clinical Early-Life Stress-Associated Depression. eNeuro. 2021;8:ENEURO.0222-20.2020