A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression: The Role of Baseline Inflammatory Biomarkers | Depressive Disorders | JAMA Psychiatry | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.239.177.24. Please contact the publisher to request reinstatement.

Author Andrew H. Miller, MD discusses A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression

1.
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.  Am J Psychiatry. 2006;163(11):1905-191717074942PubMedGoogle ScholarCrossref
2.
Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression.  Biol Psychiatry. 2009;65(9):732-74119150053PubMedGoogle ScholarCrossref
3.
Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder.  Neuropsychopharmacology. 2000;22(4):370-37910700656PubMedGoogle ScholarCrossref
4.
Papakostas GI, Shelton RC, Kinrys G, Henry ME, Bakow BR, Lipkin SH, Pi B, Thurmond L, Bilello JA. Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a Pilot and Replication Study [published ahead of print December 13, 2011].  Mol PsychiatryGoogle Scholar
5.
Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis [published correction appears in Am J Psychiatry. 2012;169(4):439].  Am J Psychiatry. 2012;169(2):141-15122420036PubMedGoogle ScholarCrossref
6.
Rush AJ, Wisniewski SR, Warden D, Luther JF, Davis LL, Fava M, Nierenberg AA, Trivedi MH. Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features.  Arch Gen Psychiatry. 2008;65(8):870-88018678792PubMedGoogle ScholarCrossref
7.
Nathan C. Epidemic inflammation: pondering obesity.  Mol Med. 2008;14(7-8):485-49218431463PubMedGoogle Scholar
8.
Danese A, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment.  Arch Gen Psychiatry. 2008;65(4):409-41518391129PubMedGoogle ScholarCrossref
9.
Pace TW, Heim CM. A short review on the psychoneuroimmunology of posttraumatic stress disorder: from risk factors to medical comorbidities.  Brain Behav Immun. 2011;25(1):6-1320934505PubMedGoogle ScholarCrossref
10.
Bouhuys AL, Flentge F, Oldehinkel AJ, van den Berg MD. Potential psychosocial mechanisms linking depression to immune function in elderly subjects.  Psychiatry Res. 2004;127(3):237-24515296823PubMedGoogle ScholarCrossref
11.
Katon W, Unützer J, Russo J. Major depression: the importance of clinical characteristics and treatment response to prognosis.  Depress Anxiety. 2010;27(1):19-2619798766PubMedGoogle ScholarCrossref
12.
Zhu CB, Lindler KM, Owens AW, Daws LC, Blakely RD, Hewlett WA. Interleukin-1 receptor activation by systemic lipopolysaccharide induces behavioral despair linked to MAPK regulation of CNS serotonin transporters.  Neuropsychopharmacology. 2010;35(13):2510-252020827273PubMedGoogle ScholarCrossref
13.
Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters.  Neuropsychopharmacology. 2006;31(10):2121-213116452991PubMedGoogle Scholar
14.
Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D. Neopterin production, tryptophan degradation, and mental depression—what is the link?  Brain Behav Immun. 2002;16(5):590-59512401473PubMedGoogle ScholarCrossref
15.
Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior.  Neuropsychopharmacology. 2012;37(1):137-16221918508PubMedGoogle ScholarCrossref
16.
Neurauter G, Schröcksnadel K, Scholl-Bürgi S, Sperner-Unterweger B, Schubert C, Ledochowski M, Fuchs D. Chronic immune stimulation correlates with reduced phenylalanine turnover.  Curr Drug Metab. 2008;9(7):622-62718781914PubMedGoogle ScholarCrossref
17.
Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS. Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior.  Proc Natl Acad Sci U S A. 2010;107(6):2669-267420133768PubMedGoogle ScholarCrossref
18.
Goshen I, Kreisel T, Ben-Menachem-Zidon O, Licht T, Weidenfeld J, Ben-Hur T, Yirmiya R. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression.  Mol Psychiatry. 2008;13(7):717-72817700577PubMedGoogle ScholarCrossref
19.
Koo JW, Duman RS. IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress.  Proc Natl Acad Sci U S A. 2008;105(2):751-75618178625PubMedGoogle ScholarCrossref
20.
Perera TD, Dwork AJ, Keegan KA, Thirumangalakudi L, Lipira CM, Joyce N, Lange C, Higley JD, Rosoklija G, Hen R, Sackeim HA, Coplan JD. Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates.  PLoS One. 2011;6(4):e1760021525974PubMedGoogle ScholarCrossref
21.
Tilleux S, Hermans E. Neuroinflammation and regulation of glial glutamate uptake in neurological disorders.  J Neurosci Res. 2007;85(10):2059-207017497670PubMedGoogle ScholarCrossref
22.
Ida T, Hara M, Nakamura Y, Kozaki S, Tsunoda S, Ihara H. Cytokine-induced enhancement of calcium-dependent glutamate release from astrocytes mediated by nitric oxide.  Neurosci Lett. 2008;432(3):232-23618255223PubMedGoogle ScholarCrossref
23.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL. A meta-analysis of cytokines in major depression.  Biol Psychiatry. 2010;67(5):446-45720015486PubMedGoogle ScholarCrossref
24.
Raison CL, Borisov AS, Woolwine BJ, Massung B, Vogt G, Miller AH. Interferon-alpha effects on diurnal hypothalamic-pituitary-adrenal axis activity: relationship with proinflammatory cytokines and behavior.  Mol Psychiatry. 2010;15(5):535-54718521089PubMedGoogle ScholarCrossref
25.
Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, Lalla D, Woolley M, Jahreis A, Zitnik R, Cella D, Krishnan R. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial.  Lancet. 2006;367(9504):29-3516399150PubMedGoogle ScholarCrossref
26.
Persoons P, Vermeire S, Demyttenaere K, Fischler B, Vandenberghe J, Van Oudenhove L, Pierik M, Hlavaty T, Van Assche G, Noman M, Rutgeerts P. The impact of major depressive disorder on the short- and long-term outcome of Crohn's disease treatment with infliximab.  Aliment Pharmacol Ther. 2005;22(2):101-11016011668PubMedGoogle ScholarCrossref
27.
Monk JP, Phillips G, Waite R, Kuhn J, Schaaf LJ, Otterson GA, Guttridge D, Rhoades C, Shah M, Criswell T, Caligiuri MA, Villalona-Calero MA. Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients.  J Clin Oncol. 2006;24(12):1852-185916622259PubMedGoogle ScholarCrossref
28.
Silverman MN, Macdougall MG, Hu F, Pace TW, Raison CL, Miller AH. Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice.  Mol Psychiatry. 2007;12(4):408-41717389906PubMedGoogle ScholarCrossref
29.
Simen BB, Duman CH, Simen AA, Duman RS. TNFalpha signaling in depression and anxiety: behavioral consequences of individual receptor targeting.  Biol Psychiatry. 2006;59(9):775-78516458261PubMedGoogle ScholarCrossref
30.
Maes M. Evidence for an immune response in major depression: a review and hypothesis.  Prog Neuropsychopharmacol Biol Psychiatry. 1995;19(1):11-387708925PubMedGoogle ScholarCrossref
31.
Kent S, Bluthé RM, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development.  Trends Pharmacol Sci. 1992;13(1):24-281542935PubMedGoogle ScholarCrossref
32.
Kircik LH. Doxycycline and minocycline for the management of acne: a review of efficacy and safety with emphasis on clinical implications.  J Drugs Dermatol. 2010;9(11):1407-141121061764PubMedGoogle Scholar
33.
Langley RE, Burdett S, Tierney JF, Cafferty F, Parmar MK, Venning G. Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?  Br J Cancer. 2011;105(8):1107-111321847126PubMedGoogle ScholarCrossref
34.
Wang YX, Gao JX, Wang XY, Zhang L, Liu CM. Antiproliferative effects of selective cyclooxygenase-2 inhibitor modulated by nimotuzumab in estrogen-dependent breast cancer cells [published ahead of print January 18, 2012].  Tumour BiolGoogle Scholar
35.
Hu F, Wang X, Pace TW, Wu H, Miller AH. Inhibition of COX-2 by celecoxib enhances glucocorticoid receptor function.  Mol Psychiatry. 2005;10(5):426-42815700047PubMedGoogle ScholarCrossref
36.
Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis.  Psychosom Med. 2009;71(2):171-18619188531PubMedGoogle ScholarCrossref
37.
Sluzewska A, Sobieska M, Rybakowski JK. Changes in acute-phase proteins during lithium potentiation of antidepressants in refractory depression.  Neuropsychobiology. 1997;35(3):123-1279170116PubMedGoogle ScholarCrossref
38.
Gimeno D, Kivimäki M, Brunner EJ, Elovainio M, De Vogli R, Steptoe A, Kumari M, Lowe GD, Rumley A, Marmot MG, Ferrie JE. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study.  Psychol Med. 2009;39(3):413-42318533059PubMedGoogle ScholarCrossref
39.
Louis E, Vermeire S, Rutgeerts P, De Vos M, Van Gossum A, Pescatore P, Fiasse R, Pelckmans P, Reynaert H, D’Haens G, Malaise M, Belaiche J. A positive response to infliximab in Crohn disease: association with a higher systemic inflammation before treatment but not with -308 TNF gene polymorphism.  Scand J Gastroenterol. 2002;37(7):818-82412190096PubMedGoogle Scholar
40.
Arends S, Brouwer E, van der Veer E, Groen H, Leijsma MK, Houtman PM, Th A Jansen TL, Kallenberg CG, Spoorenberg A. Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study.  Arthritis Res Ther. 2011;13(3):R9421689401PubMedGoogle ScholarCrossref
41.
Bower JE, Ganz PA, Aziz N, Fahey JL. Fatigue and proinflammatory cytokine activity in breast cancer survivors.  Psychosom Med. 2002;64(4):604-61112140350PubMedGoogle Scholar
42.
Schröder J, Stüber F, Gallati H, Schade FU, Kremer B. Pattern of soluble TNF receptors I and II in sepsis.  Infection. 1995;23(3):143-1487499002PubMedGoogle ScholarCrossref
43.
Aderka D, Engelmann H, Maor Y, Brakebusch C, Wallach D. Stabilization of the bioactivity of tumor necrosis factor by its soluble receptors.  J Exp Med. 1992;175(2):323-3291310100PubMedGoogle ScholarCrossref
44.
First MB, Spitzer RL, Gibbon M, Williams JB. Structured Clinical Interview for DSM-IV. Washington, DC: American Psychiatric Press; 1997
45.
Petersen T, Papakostas GI, Posternak MA, Kant A, Guyker WM, Iosifescu DV, Yeung AS, Nierenberg AA, Fava M. Empirical testing of two models for staging antidepressant treatment resistance.  J Clin Psychopharmacol. 2005;25(4):336-34116012276PubMedGoogle ScholarCrossref
46.
Trivedi MH, Rush AJ, Ibrahim HM, Carmody TJ, Biggs MM, Suppes T, Crismon ML, Shores-Wilson K, Toprac MG, Dennehy EB, Witte B, Kashner TM. The Inventory of Depressive Symptomatology, Clinician Rating (IDS-C) and Self-Report (IDS-SR), and the Quick Inventory of Depressive Symptomatology, Clinician Rating (QIDS-C) and Self-Report (QIDS-SR) in public sector patients with mood disorders: a psychometric evaluation.  Psychol Med. 2004;34(1):73-8214971628PubMedGoogle ScholarCrossref
47.
Hamilton M. A rating scale for depression.  J Neurol Neurosurg Psychiatry. 1960;23:56-6214399272PubMedGoogle ScholarCrossref
48.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician.  J Psychiatr Res. 1975;12(3):189-1981202204PubMedGoogle ScholarCrossref
49.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO III, Criqui M, Fadl YY, Fortmann SP, Hong Y, Myers GL, Rifai N, Smith SC Jr, Taubert K, Tracy RP, Vinicor F.Centers for Disease Control and Prevention; American Heart Association.  Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association.  Circulation. 2003;107(3):499-51112551878PubMedGoogle ScholarCrossref
50.
Rutgeerts P, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Hanauer SB. Comparison of scheduled and episodic treatment strategies of infliximab in Crohn's disease.  Gastroenterology. 2004;126(2):402-41314762776PubMedGoogle ScholarCrossref
51.
Guy W, edEarly Clinical Drug Evaluation Program Assessment Manual for Psychopharmacology, Revised. Rockville, MD: National Institute of Mental Health; 1976. Publication 76-338
52.
McGrath PJ, Stewart JW, Fava M, Trivedi MH, Wisniewski SR, Nierenberg AA, Thase ME, Davis L, Biggs MM, Shores-Wilson K, Luther JF, Niederehe G, Warden D, Rush AJ. Tranylcypromine versus venlafaxine plus mirtazapine following three failed antidepressant medication trials for depression: a STAR*D report.  Am J Psychiatry. 2006;163(9):1531-1541; quiz 166616946177PubMedGoogle ScholarCrossref
53.
Undurraga J, Baldessarini RJ. Randomized, placebo-controlled trials of antidepressants for acute major depression: thirty-year meta-analytic review.  Neuropsychopharmacology. 2012;37(4):851-86422169941PubMedGoogle ScholarCrossref
54.
National Collaborating Centre for Mental Health.  Depression: Management of Depression in Primary and Secondary Care (National Clinical Practice Guideline 23). London, England: National Institute for Clinical Excellence; 2004
55.
Capuron L, Pagnoni G, Drake DF, Woolwine BJ, Spivey JR, Crowe RJ, Votaw JR, Goodman MM, Miller AH. Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alpha administration.  Arch Gen PsychiatryIn pressGoogle Scholar
56.
Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward.  Biol Psychiatry. 2010;68(8):748-75420719303PubMedGoogle ScholarCrossref
57.
Brydon L, Harrison NA, Walker C, Steptoe A, Critchley HD. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans.  Biol Psychiatry. 2008;63(11):1022-102918242584PubMedGoogle ScholarCrossref
58.
Eisenberger NI, Lieberman MD. Why rejection hurts: a common neural alarm system for physical and social pain.  Trends Cogn Sci. 2004;8(7):294-30015242688PubMedGoogle ScholarCrossref
59.
Capuron L, Pagnoni G, Demetrashvili M, Woolwine BJ, Nemeroff CB, Berns GS, Miller AH. Anterior cingulate activation and error processing during interferon-alpha treatment.  Biol Psychiatry. 2005;58(3):190-19616084839PubMedGoogle ScholarCrossref
60.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Dolan RJ, Critchley HD. Neural origins of human sickness in interoceptive responses to inflammation.  Biol Psychiatry. 2009;66(5):415-42219409533PubMedGoogle ScholarCrossref
61.
Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.  Biol Psychiatry. 2009;66(5):407-41419423079PubMedGoogle ScholarCrossref
62.
Torres-Platas SG, Hercher C, Davoli MA, Maussion G, Labonté B, Turecki G, Mechawar N. Astrocytic hypertrophy in anterior cingulate white matter of depressed suicides.  Neuropsychopharmacology. 2011;36(13):2650-265821814185PubMedGoogle ScholarCrossref
63.
Steiner J, Bielau H, Brisch R, Danos P, Ullrich O, Mawrin C, Bernstein HG, Bogerts B. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide.  J Psychiatr Res. 2008;42(2):151-15717174336PubMedGoogle ScholarCrossref
64.
Krupnick JL, Sotsky SM, Simmens S, Moyer J, Elkin I, Watkins J, Pilkonis PA. The role of the therapeutic alliance in psychotherapy and pharmacotherapy outcome: findings in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.  J Consult Clin Psychol. 1996;64(3):532-5398698947PubMedGoogle ScholarCrossref
65.
Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood.  Brain Behav Immun. 2010;24(4):558-56320043983PubMedGoogle ScholarCrossref
66.
Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis.  Brain Behav Immun. 2011;25(2):181-21320970492PubMedGoogle ScholarCrossref
67.
Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans.  Proc Natl Acad Sci U S A. 2011;108(22):9262-926721518864PubMedGoogle ScholarCrossref
68.
Banks WA, Erickson MA. The blood-brain barrier and immune function and dysfunction.  Neurobiol Dis. 2010;37(1):26-3219664708PubMedGoogle ScholarCrossref
69.
Raison CL, Borisov AS, Majer M, Drake DF, Pagnoni G, Woolwine BJ, Vogt GJ, Massung B, Miller AH. Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression.  Biol Psychiatry. 2009;65(4):296-30318801471PubMedGoogle ScholarCrossref
70.
Chio CC, Lin JW, Chang MW, Wang CC, Kuo JR, Yang CZ, Chang CP. Therapeutic evaluation of etanercept in a model of traumatic brain injury.  J Neurochem. 2010;115(4):921-92920796174PubMedGoogle ScholarCrossref
71.
Kikuchi H, Aramaki K, Hirohata S. Effect of infliximab in progressive neuro-Behçet's syndrome.  J Neurol Sci. 2008;272(1-2):99-10518550081PubMedGoogle ScholarCrossref
72.
Irwin MR, Olmstead R, Valladares EM, Breen EC, Ehlers CL. Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence.  Biol Psychiatry. 2009;66(2):191-19519185287PubMedGoogle ScholarCrossref
Original Article
January 2013

A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant Depression: The Role of Baseline Inflammatory Biomarkers

Author Affiliations

Author Affiliations: Division of Digestive Diseases (Dr Rutherford), Departments of Psychiatry and Behavioral Sciences (Drs Raison, Schettler, Drake, Haroon, and Miller and Ms Woolwine) and Medicine (Dr Rutherford), School of Medicine, and Department of Biostatistics, Rollins School of Public Health (Mr Shuo), Emory University, Atlanta, Georgia, and Department of Psychiatry, University of Arizona College of Medicine, Tucson, Arizona (Dr Raison).

JAMA Psychiatry. 2013;70(1):31-41. doi:10.1001/2013.jamapsychiatry.4
Abstract

Context Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants.

Objectives To determine whether inhibition of the inflammatory cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), TNF, and its soluble receptors, predicts treatment response.

Design Double-blind, placebo-controlled, randomized clinical trial.

Setting Outpatient infusion center at Emory University in Atlanta, Georgia.

Participants A total of 60 medically stable outpatients with major depression who were either on a consistent antidepressant regimen (n = 37) or medication-free (n = 23) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method.

Interventions Three infusions of the TNF antagonist infliximab (5 mg/kg) (n = 30) or placebo (n = 30) at baseline and weeks 2 and 6 of a 12-week trial.

Main Outcome Measures The 17-item Hamilton Scale for Depression (HAM-D) scores.

Results No overall difference in change of HAM-D scores between treatment groups across time was found. However, there was a significant interaction between treatment, time, and log baseline hs-CRP concentration (P = .01), with change in HAM-D scores (baseline to week 12) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less. Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response (≥50% reduction in HAM-D score at any point during treatment) of 62% (8 of 13 patients) in infliximab-treated patients vs 33% (3 of 9 patients) in placebo-treated patients (P = .19). Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders (P < .05), and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders (P < .01). Dropouts and adverse events were limited and did not differ between groups.

Conclusions This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers.

Trial Registration clinicaltrials.gov Identifier: NCT00463580.

×