The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine

• Published in: Molecular psychiatry Vol. 11; no. 7; pp. 680 - 684
• Main Authors: Müller, N, Schwarz, M J, Dehning, S, Douhe, A, Cerovecki, A, Goldstein-Müller, B, Spellmann, I, Hetzel, G, Maino, K, Kleindienst, N, Möller, H-J, Arolt, V, Riedel, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2006; Nature Publishing Group
• Subjects: Adrenergic Uptake Inhibitors; Adult; Adult and adolescent clinical studies; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - therapeutic use; Anti-inflammatory agents; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Celecoxib; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase-2; Cytokines; Depression; Depressive Disorder - drug therapy; Depressive Disorder - physiopathology; Dinoprostone - analysis; Dinoprostone - biosynthesis; Double-Blind Method; Double-blind studies; Drug Therapy, Combination; Female; Humans; Inflammation; Inflammation - drug therapy; Inflammation - physiopathology; Interleukin-6 - biosynthesis; Lorazepam - administration & dosage; Lorazepam - therapeutic use; Male; Medical sciences; Medicine; Medicine & Public Health; Mental depression; Middle Aged; Mood disorders; Morpholines - administration & dosage; Morpholines - therapeutic use; Neuropharmacology; Neurosciences; original-article; Patient Dropouts; Patients; Pharmacology. Drug treatments; Pharmacotherapy; Pilot Projects; Placebos; Plasma levels; Prostaglandin E2; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychological Tests; Psychology. Psychoanalysis. Psychiatry; Psychopathology; Psychopathology. Psychiatry; Psychopharmacology; Pyrazoles - administration & dosage; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Reboxetine; Serotonin - metabolism; Severity of Illness Index; Sulfonamides - administration & dosage; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; psychoneuroimmunology; COX-2 inhibition; immunity; inflammation; major depression; Prostaglandin-endoperoxide synthase; Psychotropic; Cyclooxygenase 2 inhibitor; Reuptake inhibitor; Antidepressant agent; Inhibition; Mood disorder; Human; Reboxetine; Enzyme; Enzyme inhibitor; Depression; Inflammation; Celecoxib; Catecholamine; Chemotherapy; Treatment; Placebo; Neurotransmitter; Double blind study; Norepinephrine; Oxidoreductases
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001805

Signs of an inflammatory process, in particular increased pro-inflammatory cytokines and increased levels of prostaglandine E 2 (PGE 2 ), have repeatedly been described in major depression (MD). As cyclooxygenase-2 (COX-2) inhibitors inhibit the PGE 2 production and the production of pro-inflammatory cytokines, we performed a therapeutic trial with the COX-2 inhibitor celecoxib. In a prospective, double-blind, add-on study, 40 patients suffering from an acute depressive episode were randomly assigned to either reboxetine and celecoxib or to reboxetine plus placebo. After a wash-out period, 20 patients received 4–10 mg reboxetine plus placebo and 20 received reboxetine plus 400 mg celecoxib for 6 weeks. The treatment effect was calculated by analysis of variance. There were no significant differences between groups in age, sex, duration or severity of disease or psychopathology, or reboxetine dose or plasma levels. Over 6 weeks, both groups of patients showed significant improvement in scores of the Hamilton Depression Scale. However, the celecoxib group showed significantly greater improvement compared to the reboxetine-alone group. Additional treatment with celecoxib has significant positive effects on the therapeutic action of reboxetine with regard to depressive symptomatology. Moreover, the fact that treatment with an anti-inflammatory drug showed beneficial effects on MD indicates that inflammation is related to the pathomechanism of the disorder, although the exact mechanisms remain to become elucidated.