Antidepressant psychopharmacology: is inflammation a future target?
Abstract
Raised inflammatory setpoints have been associated with major depression and its detrimental consequences on brain function, as they lead to increased production of cytokines, changes in gene expression and activated brain microglia. Three main lines of evidence support immune-inflammatory mechanisms as targets for the treatment of depression. First, higher inflammation hampers response to antidepressants, and effective antidepressant treatment decreases inflammation. Second, conventional antidepressants share immune-modulatory and anti-inflammatory properties, which could affect inflammation during the depression. Third, anti-inflammatory and immune-modulatory treatments proved superior to placebo in randomized controlled antidepressant trials. New targets and new pharmacologic treatment for immune-mediated inflammatory diseases have been identified and tested in several medical settings and interest is warranted for testing them as antidepressants.
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Higher inflammation has been found to hamper response to antidepressant medication.
“higher inflammation has been found to hamper response to antidepressant medication (78)”
From The 2023 Impact of Inflammatory Bowel Disease in Canada: Mental Health and Inflammatory Bowel Disease (2023) · cites this paper as [78]
Cites
1 retracted
Zhao, X., Li, Y., Tian, Q., Zhu, B., & Zhao, Z. (2019) · Journal of International Medical Research · doi:10.1177/0300060518817417 · Cited by 113 · see citing works
RetractedCytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009 · see citing works
Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.4 · Cited by 1,617 · see citing works
Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa
Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073 · see citing works
Köhler, O., Benros, M. E., Nordentoft, M., Farkouh, M. E., Iyengar, R. L., Mors, O., & Krogh, J. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1611 · Cited by 941 · see citing works
Müller, N., Schwarz, M. J., Dehning, S., Douhe, A., Cerovecki, A., Goldstein-Müller, B., Spellmann, I., Hetzel, G., Maino, K., Kleindienst, N., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001805 · Cited by 794 · see citing works
Inflammation in Depression and the Potential for Anti-Inflammatory Treatment
Kohler, O., Krogh, J., Mors, O., & Eriksen Benros, M. (2016) · Current Neuropharmacology · doi:10.2174/1570159x14666151208113700 · Cited by 516 · see citing works
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., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0632-1 · Cited by 449 · see citing works
Liu, J. J., Wei, Y. B., Strawbridge, R., Bao, Y., Chang, S., Shi, L., Que, J., Gadad, B. S., Trivedi, M. H., Kelsoe, J. R., et al. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0474-5 · Cited by 429 · see citing works
Akhondzadeh, S., Jafari, S., Raisi, F., Nasehi, A. A., Ghoreishi, A., Salehi, B., Mohebbi-Rasa, S., Raznahan, M., & Kamalipour, A. (2009) · Depression and Anxiety · doi:10.1002/da.20589 · Cited by 397 · see citing works
Immune-mediated inflammatory disease therapeutics: past, present and future
McInnes, I. B., & Gravallese, E. M. (2021) · Nature reviews. Immunology · doi:10.1038/s41577-021-00603-1 · Cited by 356 · see citing works
Abbasi, S.-H., Hosseini, F., Modabbernia, A., Ashrafi, M., & Akhondzadeh, S. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.03.033 · Cited by 344 · see citing works
Neuroinflammation in Bipolar Depression
Benedetti, F., Aggio, V., Pratesi, M. L., Greco, G., & Furlan, R. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00071 · Cited by 281 · see citing works
Self-citationNettis, M. A., Lombardo, G., Hastings, C., Zajkowska, Z., Mariani, N., Nikkheslat, N., Worrell, C., Enache, D., McLaughlin, A., Kose, M., et al. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-00948-6 · Cited by 235 · see citing works
Mendlewicz, J., Kriwin, P., Oswald, P., Souery, D., Alboni, S., & Brunello, N. (2006) · International Clinical Psychopharmacology · doi:10.1097/00004850-200607000-00005 · Cited by 229 · see citing works
Effects of Lithium on Inflammation
Nassar, A., & Azab, A. N. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500038f · Cited by 218 · see citing works
Arteaga-Henríquez, G., Simon, M. S., Burger, B., Weidinger, E., Wijkhuijs, A. J. M., Arolt, V., Birkenhäger, T. K., Musil, R., Müller, N., & Drexhage, H. A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00458 · Cited by 215 · see citing works
Wang, L., Wang, R., Liu, L., Qiao, D., Baldwin, D. S., & Hou, R. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.02.021 · Cited by 192 · see citing works
Wittenberg, G. M., Stylianou, A., Zhang, Y., Sun, Y., Gupta, A., Jagannatha, P. S., Wang, D., Hsu, B. L., Curran, M. E., Khan, S. A., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0471-8 · Cited by 188 · see citing works
Rosenblat, J. D., & McIntyre, R. S. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.10.042 · Cited by 179 · see citing works
Lithium and GSK3-β Promoter Gene Variants Influence White Matter Microstructure in Bipolar Disorder
Benedetti, F., Bollettini, I., Barberi, I., Radaelli, D., Poletti, S., Locatelli, C., Pirovano, A., Lorenzi, C., Falini, A., Colombo, C., et al. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.172 · Cited by 164 · see citing works
Self-citationInflammatory cytokines influence measures of white matter integrity in Bipolar Disorder
Benedetti, F., Poletti, S., Hoogenboezem, T. A., Mazza, E., Ambrée, O., de Wit, H., Wijkhuijs, A. J. M., Locatelli, C., Bollettini, I., Colombo, C., et al. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.05.047 · Cited by 151 · see citing works
Self-citationPoletti, S., Vai, B., Mazza, M. G., Zanardi, R., Lorenzi, C., Calesella, F., Cazzetta, S., Branchi, I., Colombo, C., Furlan, R., et al. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110136 · Cited by 127 · see citing works
Self-citationMechanisms of action of fluvoxamine for COVID-19: a historical review
Hashimoto, Y., Suzuki, T., & Hashimoto, K. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01432-3 · Cited by 125 · see citing works
The association of depression with platelet activation: evidence for a treatment effect
Morel‐Kopp, M., McLean, L., Chen, Q., Tofler, G. H., Tennant, C., Maddison, V., & Wård, C. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03278.x · Cited by 108 · see citing works
NSAIDs Are Associated with Lower Depression Scores in Patients with Osteoarthritis
Iyengar, R. L., Gandhi, S., Aneja, A., Thorpe, K. E., Razzouk, L., Greenberg, J., Mosovich, S., & Farkouh, M. E. (2013) · The American Journal of Medicine · doi:10.1016/j.amjmed.2013.02.037 · Cited by 106 · see citing works
Molteni, R., Macchi, F., Zecchillo, C., Dell’Agli, M., Colombo, E., Calabrese, F., Guidotti, G., Racagni, G., & Riva, M. A. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.03.008 · Cited by 106 · see citing works
Fields, C., Drye, L., Vaidya, V., & Lyketsos, C. (2012) · The American Journal of Geriatric Psychiatry · doi:10.1097/jgp.0b013e318227f4da · Cited by 96 · see citing works
Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression
Simon, M. S., Schiweck, C., Arteaga-Henríquez, G., Poletti, S., Haarman, B. C. M., Dik, W. A., Schwarz, M., Vrieze, E., Mikova, O., Joergens, S., et al. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2021.110391 · Cited by 93 · see citing works
Self-citationInflammation-Associated Synaptic Alterations as Shared Threads in Depression and Multiple Sclerosis
Bruno, A., Dolcetti, E., Rizzo, F. R., Fresegna, D., Musella, A., Gentile, A., Vito, F. D., Caioli, S., Guadalupi, L., Bullitta, S., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00169 · Cited by 82 · see citing works
Effect of Selective Serotonin Reuptake Inhibitors on Platelet Activation
Schlienger, R. G., & Meier, C. R. (2003) · American Journal of Cardiovascular Drugs · doi:10.2165/00129784-200303030-00001 · Cited by 78 · see citing works
Higher Baseline Proinflammatory Cytokines Mark Poor Antidepressant Response in Bipolar Disorder
Benedetti, F., Poletti, S., Hoogenboezem, T. A., Locatelli, C., de Wit, H., Wijkhuijs, A. J. M., Colombo, C., & Drexhage, H. A. (2017) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.16m11310 · Cited by 74 · see citing works
Self-citationBenedetti, F., Lucca, A., Brambilla, F., Colombo, C., & Smeraldi, E. (2002) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(02)00255-5 · Cited by 73 · see citing works
Self-citationBrain-immune crosstalk in the treatment of major depressive disorder
Branchi, I., Poggini, S., Capuron, L., Benedetti, F., Poletti, S., Tamouza, R., Drexhage, H. A., Penninx, B. W. J. H., & Pariante, C. M. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.11.016 · Cited by 64 · see citing works
Self-citationHigher Baseline Interleukin-1β and TNF-α Hamper Antidepressant Response in Major Depressive Disorder
Benedetti, F., Poletti, S., Vai, B., Mazza, M. G., Lorenzi, C., Brioschi, S., Aggio, V., Branchi, I., Colombo, C., Furlan, R., et al. (2021) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.11.009 · Cited by 62 · see citing works
Self-citationCan Cytokine Blocking Prevent Depression in COVID-19 Survivors?
Benedetti, F., Mazza, M., Cavalli, G., Ciceri, F., Dagna, L., & Rovere-Querini, P. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-020-09966-z · Cited by 55 · see citing works
Self-citationMarkers of neuroinflammation influence measures of cortical thickness in bipolar depression
Poletti, S., Leone, G., Hoogenboezem, T. A., Ghiglino, D., Vai, B., de Wit, H., Wijkhuijs, A. J. M., Locatelli, C., Colombo, C., Drexhage, H. A., et al. (2019) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2019.01.009 · Cited by 54 · see citing works
Self-citationBerardis, D. D., Fornaro, M., Orsolini, L., Iasevoli, F., Tomasetti, C., de Bartolomeis, A., Serroni, N., Lauretis, I. D., Girinelli, G., Mazza, M., et al. (2016) · CNS Spectrums · doi:10.1017/s1092852916000572 · Cited by 52 · see citing works
Self-citationChittaranjan, A., Chethan, K. B., & Surya, S. (2013) · International Clinical Psychopharmacology · doi:10.1097/yic.0b013e32835d735d · Cited by 51 · see citing works
Natural killer cells protect white matter integrity in bipolar disorder
Furlan, R., Melloni, E. M. T., Finardi, A., Vai, B., Toro, S. D., Aggio, V., Battistini, L., Borsellino, G., Manfredi, E., Falini, A., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.06.037 · Cited by 49 · see citing works
Self-citationPashaei, Y. (2021) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2021.03.010 · Cited by 46 · see citing works
Circulating inflammatory markers impact cognitive functions in bipolar depression
Poletti, S., Mazza, M. G., Calesella, F., Vai, B., Lorenzi, C., Manfredi, E., Colombo, C., Zanardi, R., & Benedetti, F. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.05.071 · Cited by 37 · see citing works
Self-citationNettis, M. A. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100335 · Cited by 30 · see citing works
Poletti, S., Mazza, M. G., Vai, B., Lorenzi, C., Colombo, C., & Benedetti, F. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.590095 · Cited by 25 · see citing works
Self-citationElnazer, H. Y., Sampson, A. P., & Baldwin, D. S. (2021) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000356 · Cited by 21 · see citing works
Benedetti, F., Dallaspezia, S., Melloni, E. M. T., Lorenzi, C., Zanardi, R., Barbini, B., & Colombo, C. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.740686 · Cited by 17 · see citing works
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Graff, L. A., Geist, R., Kuenzig, M. E., Benchimol, E. I., Kaplan, G. G., Windsor, J. W., Bitton, A., Coward, S., Jones, J. L., Lee, K., et al. (2023) · Journal of the Canadian Association of Gastroenterology · doi:10.1093/jcag/gwad012 · Cited by 30 · see citing works
“While antidepressant medications may have beneficial effects for depression and anxiety occurring in the context of IBD, there is a need for further evaluation as higher inflammation has been found to hamper response to antidepressant medication (78), and there remains little data on efficacy directly in IBD (56,79).”
BackgroundScala, M., Fabbri, C., Fusar-Poli, P., Di Lorenzo, G., Ferrara, M., Amerio, A., Fusar-Poli, L., Pichiecchio, A., Asteggiano, C., Menchetti, M., et al. (2024) · CNS Spectrums · doi:10.1017/s1092852924002268 · Cited by 9 · see citing works
“Furthermore, exploring other possible mechanisms of action, such as potential anti-inflammatory properties, 111 may provide additional support for benefits in various disorders, including depressive 112 and anxiety disorders.”
- Authors
- Benedetti, F., Zanardi, R., & Mazza, M. G.
- Affiliations
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Benedetti, Francesco
- Venue
- International Clinical Psychopharmacology
- Published
- 2022-03-31
- Volume
- 37
- Issue
- 3
- Pages
- 79-81
- ISSN
- 0268-1315 (ISSN-L)
- OpenAlex
- W4220929327
- Cited by
- 45
- References
- 46
- Citations by year
- 2026: 3 · 2025: 11 · 2024: 16 · 2023: 10 · 2022: 5
- FWCI
- 3.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Clinical Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- depression, inflammation, cytokines, microglia, antidepressants, immunomodulation, anti-inflammatory therapy, antidepressant response, gene expression, immune-mediated inflammatory diseases
- MeSH terms
- Anti-Inflammatory Agents, Antidepressive Agents, Depressive Disorder, Major, Major Depressive Disorder, Humans, Inflammation, Psychopharmacology
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