Authors : Priyash P. Ajmire; Vaishnavi G. Mirchapure

Volume/Issue : Volume 9 - 2024, Issue 9 - September

Google Scholar : https://tinyurl.com/yvsphb76

Scribd : https://tinyurl.com/47ssb33z

DOI : https://doi.org/10.38124/ijisrt/IJISRT24SEP941

Note : A published paper may take 4-5 working days from the publication date to appear in PlumX Metrics, Semantic Scholar, and ResearchGate.

Abstract : Depression and anxiety are prevalent mental health illnesses that have significant worldwide consequences, impacting millions of individuals who experience chronic feelings of melancholy, excessive worry, and significant limitations in their everyday activities. Major Depressive Disorder (MDD) and several anxiety disorders, such as Generalized Anxiety Disorder (GAD), panic disorder, and social anxiety disorder, are defined by severe symptoms that make their treatment more difficult, especially when these illnesses happen at the same time. Gaining a comprehensive understanding of the neuropharmacological mechanisms that are responsible for these illnesses is of utmost importance in order to facilitate the development of treatments that are very effective. The existing therapy approaches, such as Selective Serotonin Reuptake Inhibitors (SSRIs) and newer antidepressants, provide partial relief but do not work for everyone. This suggests that further research is necessary to explore the underlying neurological causes of these illnesses. Recent developments in the field of neuropharmacology have provided insights into the significance of imbalances in neurotransmitters, specifically serotonin, norepinephrine, and dopamine, in the underlying mechanisms of mood disorders. Disruption of the Hypothalamic-Pituitary-Adrenal (HPA) axis and neuroinflammation are also major factors in the development of these illnesses. This review offers a thorough examination of these pathways, emphasizing the functions of neurotransmitter systems, neurostimulation treatments, and developing pharmaceutical medicines. This study investigates the possibility of new neuropharmacological targets, including NMDA receptor antagonists, AMPA receptor modulators, and neurosteroids, to enhance the effectiveness of treatment. In addition, it discusses non-pharmacological methods such as Cognitive Behavioral Therapy (CBT), physical activity, and mindfulness, highlighting their neuropharmacological foundations and advantages.This review is to provide an in-depth investigation of the current understanding and approaches to addressing depression and anxiety by including latest research findings. The text discusses crucial therapeutic approaches and presents potential areas of future study that could improve treatment results for these prevalent mental health illnesses.

Keywords : Depression, Major Depressive Disorder (MDD), GABAergic System, Pharmacogenomics, Biomarkers.

References :

1. Brown, C., 2001. Depression and anxiety disorders.. Obstetrics and gynecology clinics of North America, 28 2, pp. 241-68 . https://doi.org/10.1016/S0889-8545(05)70199-6.
2. Coughlin, S., 2012. Anxiety and Depression: Linkages with Viral Diseases. Public Health Reviews, 34. https://doi.org/10.1007/BF03391675.
3. Milev, R., Giacobbe, P., Kennedy, S., Blumberger, D., Daskalakis, Z., Downar, J., Modirrousta, M., Patry, S., Vila-Rodriguez, F., Lam, R., MacQueen, G., Parikh, S., & Ravindran, A., 2016. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. The Canadian Journal of Psychiatry, 61, pp. 561 - 575. https://doi.org/10.1177/0706743716660033.
4. Milev, R., Giacobbe, P., Kennedy, S., Blumberger, D., Daskalakis, Z., Downar, J., Modirrousta, M., Patry, S., Vila-Rodriguez, F., Lam, R., MacQueen, G., Parikh, S., & Ravindran, A., 2016. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder. The Canadian Journal of Psychiatry, 61, pp. 561 - 575. https://doi.org/10.1177/0706743716660033.
5. Milligen, B., Verhoeven, J., Schmaal, L., Velzen, L., Révész, D., Black, C., Han, L., Horsfall, M., Batelaan, N., Balkom, A., Schaik, D., Oppen, P., & Penninx, B., 2019. The impact of depression and anxiety treatment on biological aging and metabolic stress: study protocol of the Mood treatment with antidepressants or running (MOTAR) study. BMC Psychiatry, 19. https://doi.org/10.1186/s12888-019-2404-0.
6. Ressler, K., & Nemeroff, C., 2000. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depression and Anxiety, 12. 3.0.CO;2-4" target="_blank">https://doi.org/10.1002/1520-6394(2000)12:1+<2::AID-DA2>3.0.CO;2-4.
7. Baker,  G.,  &  Mitchell,  N., 2008. Depression: Chemical Mechanisms. ,  pp. 1-13. https://doi.org/10.1002/9780470048672.WECB674.
8. Blier, P., 2001. Crosstalk between the norepinephrine and serotonin systems and its role in the antidepressant response.. Journal of psychiatry & neuroscience : JPN, 26 Suppl, pp. S3-10 .
9. Leonard, B., 2005. The HPA and immune axes in stress: the involvement of the serotonergic system. European Psychiatry, 20, pp. S302 - S306. https://doi.org/10.1016/S0924-9338(05)80180-4.
10. Troubat, R., Barone, P., Leman, S., Desmidt, T., Cressant, A., Atanasova, B., Brizard, B., Hage, W., Surget, A., Belzung, C., & Camus, V., 2020. Neuroinflammation and depression: A review. European Journal of Neuroscience, 53, pp. 151 - 171. https://doi.org/10.1111/ejn.14720.
11. Kim, Y., Na, K., Myint, A., & Leonard, B., 2016. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 64, pp. 277-284. https://doi.org/10.1016/j.pnpbp.2015.06.008.
12. Olsson, T., Barcellos, L., & Alfredsson, L., 2017. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nature Reviews Neurology, 13, pp. 25-36. https://doi.org/10.1038/nrneurol.2016.187.
13. Klengel, T., & Binder, E., 2015. Epigenetics of Stress-Related Psychiatric Disorders and Gene × Environment Interactions. Neuron, 86, pp. 1343-1357. https://doi.org/10.1016/j.neuron.2015.05.036.
14. Denham, J., 2018. Exercise and epigenetic inheritance of disease risk. Acta Physiologica, 222. https://doi.org/10.1111/apha.12881.
15. Ling, C., & Groop, L., 2009. Epigenetics: A Molecular Link Between Environmental Factors and Type 2 Diabetes. Diabetes, 58, pp. 2718 - 2725. https://doi.org/10.2337/db09-1003.
16. Godfrey, K., Lillycrop, K., Burdge, G., Gluckman, P., & Hanson, M., 2007. Epigenetic Mechanisms and the Mismatch Concept of the Developmental Origins of Health and Disease. Pediatric Research, 61, pp. 5R10R. https://doi.org/10.1203/pdr.0b013e318045bedb.
17. Tynan, R., Weidenhofer, J., Hinwood, M., Cairns, M., Day, T., & Walker, F., 2012. A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain, Behavior, and Immunity, 26, pp. 469-479. https://doi.org/10.1016/j.bbi.2011.12.011.
18. Shelton, R., 2004. The dual-action hypothesis: does pharmacology matter?. The Journal of clinical psychiatry, 65 Suppl 17, pp. 5-10 .
19. Thase, M., 2008. Are SNRIs more effective than SSRIs? A review of the current state of the controversy.. Psychopharmacology bulletin, 41 2, pp. 58-85 .
20. Gillman, P., 2007. Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. British Journal of Pharmacology, 151. https://doi.org/10.1038/sj.bjp.0707253.
21. Lader, M., 1987. Long-term anxiolytic therapy: the issue of drug withdrawal.. The Journal of clinical psychiatry, 48 Suppl, pp. 12-6 .
22. Sussman, N., 1998. Anxiolytic antidepressant augmentation.. The Journal of clinical psychiatry, 59 Suppl 5, pp. 42-8; discussion 49-50 .
23. Takeuchi, T., Owa, T., Nishino, T., & Kamei, C., 2010. Assessing anxiolytic-like effects of selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors using the elevated plus maze in mice.. Methods and findings in experimental and clinical pharmacology, 32 2, pp. 113-21 . https://doi.org/10.1358/mf.2010.32.2.1428741.
24. Birkett, M., Shinday, N., Kessler, E., Meyer, J., Ritchie, S., & Rowlett, J., 2011. Acute anxiogenic-like effects of selective serotonin reuptake inhibitors are attenuated by the benzodiazepine diazepam in BALB/c mice. Pharmacology Biochemistry and Behavior, 98, pp. 544-551. https://doi.org/10.1016/j.pbb.2011.03.006.
25. Outhoff, K., 2016. An update on the pharmacology of anxiolytics for the anxiety, obsessive compulsive and post-traumatic stress disorders. SA Pharmaceutical Journal, 83, pp. 24-30.
26. Feighner, J., & Boyer, W., 1989. Serotonin-1A anxiolytics: an overview.. Psychopathology, 22 Suppl 1, pp. 21-6 . https://doi.org/10.1159/000284623.
27. Alvarez, E., Carrasco, J., Olivares, J., López-Gómez, V., Pérez, M., & Rejas, J., 2012. P-148 - Utilization of Concomitant Anxiolytic Treatment in Benzodiazepine-resistant Patients Initiating Pregabalin or Ssri/snri for the Treatment of Generalized Anxiety Disorder (gad). European Psychiatry, 27, pp. 1 - 1. https://doi.org/10.1016/S0924-9338(12)74315-8.
28. Lader, M., 1987. Long-term anxiolytic therapy: the issue of drug withdrawal.. The Journal of clinical psychiatry, 48 Suppl, pp. 12-6 .
29. Oyan, B., Koc, Y., Ozdemir, E., Kars, A., Turker, A., Tekuzman, G., & Kansu, E., 2005. Ifosfamide, idarubicin, and etoposide in relapsed/refractory Hodgkin disease or non-Hodgkin lymphoma: a salvage regimen with high response rates before autologous stem cell transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 11 9, pp. 688-97 . https://doi.org/10.1016/J.BBMT.2005.05.014.
30. Nikolaou, M., Pavlopoulou, A., Georgakilas, A., & Kyrodimos, E., 2018. The challenge of drug resistance in cancer treatment: a current overview. Clinical & Experimental Metastasis, 35, pp. 309 - 318. https://doi.org/10.1007/s10585-018-9903-0.
31. Robinson, D., Woerner, M., Delman, H., & Kane, J., 2005. Pharmacological treatments for first-episode schizophrenia.. Schizophrenia bulletin, 31 3, pp. 705-22 . https://doi.org/10.1093/SCHBUL/SBI032.
32. Liu, Y., He, P., Cheng, X., & Zhang, M., 2015. Long-term outcome of 31 cases of refractory acute promyelocytic leukemia treated with compound realgar natural indigo tablets administered alternately with chemotherapy.. Oncology letters, 10 2, pp. 1184-1190 . https://doi.org/10.3892/OL.2015.3308.
33. Xu, H., Li, N., Wang, G., & Cao, Y., 2023. Predictive short/long-term efficacy biomarkers and resistance mechanisms of CD19-directed CAR-T immunotherapy in relapsed/refractory B-cell lymphomas. Frontiers in Immunology, 14. https://doi.org/10.3389/fimmu.2023.1110028.
34. Jian-peng, D., Hang, L., Xiao-Ling, P., Chao-Ni, Z., Tian-Huai, Y., & Xian-Min, J., 2019. Research progress of quantum memory. Acta Physica Sinica. https://doi.org/10.7498/APS.68.20190039.
35. Jian-peng, D., Hang, L., Xiao-Ling, P., Chao-Ni, Z., Tian-Huai, Y., & Xian-Min, J., 2019. Research progress of quantum memory. Acta Physica Sinica. https://doi.org/10.7498/APS.68.20190039.
36. Jian-peng, D., Hang, L., Xiao-Ling, P., Chao-Ni, Z., Tian-Huai, Y., & Xian-Min, J., 2019. Research progress of quantum memory. Acta Physica Sinica. https://doi.org/10.7498/APS.68.20190039.
37. Jian-peng, D., Hang, L., Xiao-Ling, P., Chao-Ni, Z., Tian-Huai, Y., & Xian-Min, J., 2019. Research progress of quantum memory. Acta Physica Sinica. https://doi.org/10.7498/APS.68.20190039.
38. Jian-peng, D., Hang, L., Xiao-Ling, P., Chao-Ni, Z., Tian-Huai, Y., & Xian-Min, J., 2019. Research progress of quantum memory. Acta Physica Sinica. https://doi.org/10.7498/APS.68.20190039.
39. Goldin, P., Thurston, M., Allende, S., Moodie, C., Dixon, M., Heimberg, R., & Gross, J., 2021. Evaluation of Cognitive Behavioral Therapy vs Mindfulness Meditation in Brain Changes During Reappraisal and Acceptance Among Patients With Social Anxiety Disorder: A Randomized Clinical Trial.. JAMA psychiatry. https://doi.org/10.1001/jamapsychiatry.2021.1862.
40. Leow, Y., Rashid, N., Klainin-Yobas, P., Zhang, Z., & Wu, X., 2023. Effectiveness of mindfulness-based interventions on mental, cognitive outcomes and neuroplastic changes in older adults with mild cognitive impairment: A systematic review and meta-analysis.. Journal of advanced nursing. https://doi.org/10.1111/jan.15720.
41. Koblinsky, N., Power, K., Middleton, L., Ferland, G., & Anderson, N., 2022. The Role of the Gut Microbiome in Diet and Exercise Effects on Cognition: A Review of the Intervention Literature. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 78, pp. 195 - 205. https://doi.org/10.1093/gerona/glac166.
42. Sadee, W., Wang, D., Hartmann, K., & Toland, A., 2023. Pharmacogenomics: Driving Personalized Medicine. Pharmacological Reviews, 75, pp. 789 - 814. https://doi.org/10.1124/pharmrev.122.000810.
43. He, P., 2015. Personalized medicine: challenges in biomarker-related clinical trial design. Clinical investigation, 5, pp. 175-188. https://doi.org/10.4155/CLI.14.123.
44. Suh, K., 2012. Discovery of Novel Biomarkers for the Development of Personalized Medicine. Translational Medicine, 2012, pp. 1-2. https://doi.org/10.4172/2161-1025.S1-E001.
45. Calzaferri, F., Ruiz-Ruiz, C., Diego, A., Pascual, R., Méndez-López, I., Cano-Abad, M., Maneu, V., Ríos, C., Gandía, L., & García, A., 2020. The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases. Medicinal Research Reviews, 40, pp. 2427 - 2465. https://doi.org/10.1002/med.21710.
46. Ghosh, S., & Basu, A., 2012. Network medicine in drug design: implications for neuroinflammation.. Drug discovery today, 17 11-12, pp. 600-7 . https://doi.org/10.1016/j.drudis.2012.01.018.
47. Yap, T., Omlin, A., & Bono, J., 2013. Development of therapeutic combinations targeting major cancer signaling pathways.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 31 12, pp. 1592-605 . https://doi.org/10.1200/JCO.2011.37.6418.
48. Woodcock, J., Griffin, J., & Behrman, R., 2011. Development of novel combination therapies.. The New England journal of medicine, 364 11, pp. 985-7 . https://doi.org/10.1056/NEJMp1101548.
49. Shellhaas, R., deVeber, G., Bonkowsky, J., Augustine, E., Bassuk, A., Calame, D., Carrasco, M., Dlamini, N., Felling, R., Glass, H., Grinspan, Z., Guerriero, R., Hewitt, A., Jeste, S., Knowles, J., Lyons-Warren, A., Maricich, S., Musolino, P., Raju, G., Rho, J., Rotenberg, A., Sherr, E., Soul, J., & Ziobro, J., 2021. GeneTargeted Therapies in Pediatric Neurology: Challenges and Opportunities in Diagnosis and Delivery.. Pediatric neurology, 125, pp. 53-57 . https://doi.org/10.1016/j.pediatrneurol.2021.09.011.