The Effect of Antidepressant Medication Treatment on Serum Levels of Inflammatory Cytokines: a Meta-analysis

Overview

Journal Neuropsychopharmacology

Date 2011 Jul 29

PMID 21796103

Citations 339

Authors

Jonas Hannestad

Nicole DellaGioia

Michael Bloch

Affiliations

Soon will be listed here.

Abstract

Serum levels of inflammatory cytokines, for example, tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1 beta (IL-1β), are elevated in subjects with major depressive disorder (MDD). The reason why this occurs is unclear. Elevated levels of inflammatory cytokines could be a result of brain dysfunction in MDD. It is also possible that inflammatory cytokines contribute to depressive symptoms in MDD. If the first assumption is correct, one would expect levels to normalize with resolution of the depressive episode after treatment. Several studies have measured changes in cytokine levels during antidepressant treatment; however, the results vary. The purpose of this study was to pool all available data on changes in serum levels of TNFα, IL-6, and IL-1β during antidepressant treatment to determine whether these levels change. Studies were included if they used an approved pharmacological treatment for depression, patients had a diagnosis of MDD, and serum levels of TNFα, IL-6, and/or IL-1β were measured before and after treatment. Twenty-two studies fulfilled these criteria. Meta-analysis of these studies showed that, overall, while pharmacological antidepressant treatment reduced depressive symptoms, it did not reduce serum levels of TNFα. On the other hand, antidepressant treatment did reduce levels of IL-1β and possibly those of IL-6. Stratified subgroup analysis by class of antidepressant indicated that serotonin reuptake inhibitors may reduce levels of IL-6 and TNFα. Other antidepressants, while efficacious for depressive symptoms, did not appear to reduce cytokine levels. These results argue against the notion that resolution of a depressive episode is associated with normalization of levels of circulating inflammatory cytokines; however, the results are consistent with the possibility that inflammatory cytokines contribute to depressive symptoms and that antidepressants block the effects of inflammatory cytokines on the brain.

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References

Maes M, Meltzer H, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R . Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord. 1995; 34(4):301-9. DOI: 10.1016/0165-0327(95)00028-l. View

Pace T, Mletzko T, Alagbe O, Musselman D, Nemeroff C, Miller A . Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. Am J Psychiatry. 2006; 163(9):1630-3. DOI: 10.1176/ajp.2006.163.9.1630. View

Fornaro M, Martino M, Battaglia F, Colicchio S, Perugi G . Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation. Neuropsychiatr Dis Treat. 2011; 7:51-6. PMC: 3056173. DOI: 10.2147/NDT.S16382. View

Hinze-Selch D, Schuld A, Kraus T, Kuhn M, Uhr M, Haack M . Effects of antidepressants on weight and on the plasma levels of leptin, TNF-alpha and soluble TNF receptors: A longitudinal study in patients treated with amitriptyline or paroxetine. Neuropsychopharmacology. 2000; 23(1):13-9. DOI: 10.1016/S0893-133X(00)00089-0. View

Kagaya A, Kugaya A, Takebayashi M, Saeki T, Yamawaki S, Uchitomi Y . Plasma concentrations of interleukin-1beta, interleukin-6, soluble interleukin-2 receptor and tumor necrosis factor alpha of depressed patients in Japan. Neuropsychobiology. 2001; 43(2):59-62. DOI: 10.1159/000054867. View

Sutcigil L, Oktenli C, Musabak U, Bozkurt A, Cansever A, Uzun O . Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy. Clin Dev Immunol. 2008; 2007:76396. PMC: 2248234. DOI: 10.1155/2007/76396. View

Thayer J, Sternberg E . Neural aspects of immunomodulation: focus on the vagus nerve. Brain Behav Immun. 2010; 24(8):1223-8. PMC: 2949498. DOI: 10.1016/j.bbi.2010.07.247. View

Eller T, Vasar V, Shlik J, Maron E . Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 32(2):445-50. DOI: 10.1016/j.pnpbp.2007.09.015. View

Eller T, Vasar V, Shlik J, Maron E . Effects of bupropion augmentation on pro-inflammatory cytokines in escitalopram-resistant patients with major depressive disorder. J Psychopharmacol. 2008; 23(7):854-8. DOI: 10.1177/0269881108091077. View

10.

Gundersen Y, Opstad P, Reistad T, Thrane I, Vaagenes P . Seven days' around the clock exhaustive physical exertion combined with energy depletion and sleep deprivation primes circulating leukocytes. Eur J Appl Physiol. 2006; 97(2):151-7. DOI: 10.1007/s00421-006-0150-8. View

11.

Leo R, Di Lorenzo G, Tesauro M, Razzini C, Forleo G, Chiricolo G . Association between enhanced soluble CD40 ligand and proinflammatory and prothrombotic states in major depressive disorder: pilot observations on the effects of selective serotonin reuptake inhibitor therapy. J Clin Psychiatry. 2007; 67(11):1760-6. DOI: 10.4088/jcp.v67n1114. View

12.

Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M . Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol. 2001; 11(3):203-8. DOI: 10.1016/s0924-977x(01)00081-5. View

13.

Howren M, Lamkin D, Suls J . Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009; 71(2):171-86. DOI: 10.1097/PSY.0b013e3181907c1b. View

14.

DellaGioia N, Hannestad J . A critical review of human endotoxin administration as an experimental paradigm of depression. Neurosci Biobehav Rev. 2009; 34(1):130-43. PMC: 2795398. DOI: 10.1016/j.neubiorev.2009.07.014. View

15.

Roumestan C, Michel A, Bichon F, Portet K, Detoc M, Henriquet C . Anti-inflammatory properties of desipramine and fluoxetine. Respir Res. 2007; 8:35. PMC: 1876225. DOI: 10.1186/1465-9921-8-35. View

16.

Yirmiya R, Pollak Y, Barak O, Avitsur R, Ovadia H, Bette M . Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology. 2001; 24(5):531-44. DOI: 10.1016/S0893-133X(00)00226-8. View

17.

Tucker P, Ruwe W, Masters B, Parker D, Hossain A, Trautman R . Neuroimmune and cortisol changes in selective serotonin reuptake inhibitor and placebo treatment of chronic posttraumatic stress disorder. Biol Psychiatry. 2004; 56(2):121-8. DOI: 10.1016/j.biopsych.2004.03.009. View

18.

Shaked I, Meerson A, Wolf Y, Avni R, Greenberg D, Gilboa-Geffen A . MicroRNA-132 potentiates cholinergic anti-inflammatory signaling by targeting acetylcholinesterase. Immunity. 2009; 31(6):965-73. DOI: 10.1016/j.immuni.2009.09.019. View

19.

Miller A, Maletic V, Raison C . Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009; 65(9):732-41. PMC: 2680424. DOI: 10.1016/j.biopsych.2008.11.029. View

20.

Doering L, Cross R, Vredevoe D, Martinez-Maza O, Cowan M . Infection, depression, and immunity in women after coronary artery bypass: a pilot study of cognitive behavioral therapy. Altern Ther Health Med. 2007; 13(3):18-21. View