Effects of bupropion augmentation on pro-inflammatory cytokines in escitalopram-resistant patients with major depressive disorder

Abstract

Studies so far have provided contradictory results on immune system markers during use of antidepressants. There are no data on changes in immune parameters after treatment augmentation. The present study aimed to clarify whether the addition of bupropion in escitalopram-resistant patients with major depression causes changes in the immune system and whether treatment response could be predicted by baseline levels of cytokines. We recruited 28 depressive patients (11 men and 17 women) who did not respond to 12-week treatment with escitalopram (20 mg/d) for an augmentation trial with bupropion (150–300 mg/day). The levels of soluble interleukin-2 receptor, interleukin-8 (IL-8) and tumor-necrosis factor-α were measured before and 6 weeks after addition of bupropion. For a control group, we recruited 45 healthy volunteers (19 men and 26 women). The results indicated that the baseline levels of studied cytokines did not predict treatment response to bupropion augmentation. Concentration of IL-8 increased during the treatment similarly in both responder and non-responder groups. Although bupropion augmentation had increased the response rate in escitalopram-resistant patients, this clinical improvement was not accompanied by specific changes in studied cytokine levels.

Keywords

bupropion escitalopram interleukin-8 major depression soluble interleukin-2 receptor tumor necrosis factor-α

Get full access to this article

View all access options for this article.

References

Altschuler EL Kast RE (2005) Bupropion for fatigue and as a tumor necrosis factor-α lowering agent in primary biliary cirrhosis. Med Hypotheses 64: 118–119.

Basterzi AD Aydemir C Kisa C Aksaray S Tuzer V Yazici K (2005) IL-6 levels decrease with SSRI treatment in patients with major depression. Hum Psychopharmacol 20: 473–476.

Eller T; Vasar V; Shlik J; Maron E; (2007) Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 32: 445–450.

Fava M (2001) Augmentation and combination strategies in treatment-resistant depression. J Clin Psychiatry 62(Suppl 18): 4–11.

Frommberger UH Bauer J Haselbauer P Fräulin A Riemann D Berger M (1997) Interleukin-6-(IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci 247: 228–233.

Hinze-Selch D Schuld A Kraus T Kühn M Uhr M Haack M (2000) Effects of antidepressants on weight and on the plasma levels of leptin, TNF-alpha and soluble TNF receptors: A longitudinal study in patients with amitriptyline or paroxetine. Neuropsychopharmacology 23: 13–19.

Kast RE (2003) Anti- and pro-inflammatory considerations in antidepressant use during medical illness: bupropion lowers and mirtazapine increases circulating tumor necrosis factor-alpha levels. Gen Hosp Psychiatry 25: 495–496.

Kast RE Altschuler EL (2003) Tumor necrosis factor-alpha in hepatitis B: potential role for bupropion. J Hepatol 39: 130–135.

Kenis G Maes M (2002) Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 5: 401–412.

10.

Kraus T Haack M Schuld A Hinze-Selch D Koethe D Pollmächer T (2002) Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine. Pharmacopsychiatry 35: 220–225.

11.

Kronfol Z Remick DG (2000) Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 157: 683–694.

12.

Kubera M Kenis G Bosmans E Zieba A Dudek D Nowak G (2000) Plasma levels of interleukin-6, interöleukin-10, and interleukin-1 receptor antagonist in depression: comparison between the acute state and after remission. Pol J Pharmacol 52: 237–241.

13.

Kubera M Lin AH Kenis G Bosmans E van Bockstaele D Maes M (2001) Anti-inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J Clin Psychopharmacol 21: 199–206.

14.

Lanquillon S Krieg J-C Bening-Abu-Shach U Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22: 370–379.

15.

Maes M Bosmans E De Jongh R Kenis G Vandoolaeghe E Neels H (1997) Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9: 853–858.

16.

Maes M Meltzer HY Bosmans E Bergmans R Vandoolaeghe E Ranjan R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 18: 301–309.

17.

Marques-Deak AH Neto FL Dominguez WV Solis AC Kurcgant D Sato F (2007) Cytokine profiles in women with different subtypes of major depressive disorder. J Psychiatr Res 41: 152–159.

18.

Mikova O Yakimova R Bosmans E Kenis G Maes M (2001) Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 11: 203–208.

19.

Myint AM Leonard BE Steinbusch HWM Kim YK (2005) Th1, Th2, and Th3 cytokine alterations in major depression. J Affect Disord 88: 167–173.

20.

Nutt D Demyttenaere K Janka Z Aarre T Bourin M Canonico PL (2007) The other face of depression, reduced positive affect: the role of catecholamines in causation and cure. J Psychopharmacol 21: 461–471.

21.

O’Brien SM Scully P Fitzgerald P Scott V Dinan TG (2007) Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res 41: 326–331.

22.

Papakostas GI Nutt DJ Hallett LA Tucker VL Krishen A Fava M (2006) Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry 60: 1350–1355.

23.

Sheehan DV Lecrubier Y Sheehan KH Amorim P Janavs J Weiller E (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59: 22–33.

24.

Trivedi MH Fava M Wisniewski SR Thase ME Quitkin F Warden D Ritz L Nierenberg AA Lebowitz BD Biggs MM Luther JF Shores-Wilson K Rush AJ STAR*D Study Team (2006) Medical augmentation after the failure of SSRIs for depression. N Engl J Med 354: 1243–1252.

25.

Tuglu C Kara SH Caliyurt O Vardar E Abay E (2003) Increased serum tumor necrosis factor- alpha levels and treatment response in major depressive disorder. Psychopharmacology 170: 429–433.

26.

Zisook S Rush AJ Haight BR Clines DC Rockett CB (2006) Use of bupropion in combination with serotonin reuptake inhibitors. Biol Psychiatry 59: 203–210.