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Non-steroidal anti-inflammatory drugs and efficacy of antidepressants in major depressive disorder

  • R. Uher (a1) (a2), S. Carver (a1), R. A. Power (a1), O. Mors (a3), W. Maier (a4), M. Rietschel (a5), J. Hauser (a6), M. Z. Dernovsek (a7), N. Henigsberg (a8), D. Souery (a9), A. Placentino (a10), A. Farmer (a1) and P. McGuffin (a1)...



It has been proposed that non-steroidal anti-inflammatory drugs (NSAIDs) may interfere with the efficacy of antidepressants and contribute to treatment resistance in major depressive disorder (MDD). This effect requires replication and a test of whether it is specific to serotonin-reuptake inhibiting (SRI) antidepressants.


We tested the effect of concomitant medication with NSAIDs on the efficacy of escitalopram, a SRI antidepressant, and nortriptyline, a tricyclic antidepressant, among 811 subjects with MDD treated for up to 12 weeks in the GENDEP study. Effects of NSAIDs on improvement of depressive symptoms were tested in mixed-effect linear models. Effects on remission were tested in logistic regression. Age, sex, baseline severity and centre of recruitment were considered as potential confounding factors.


Ten percent (n=78) of subjects were taking NSAIDs during the antidepressant treatment. Older subjects were significantly more likely to take NSAIDs. After controlling for age, sex, centre of recruitment and baseline severity, concomitant medication with NSAIDs did not significantly influence the efficacy of escitalopram [β=0.035, 95% confidence interval (CI) −0.145 to 0.215, p=0.704] or nortriptyline (β=0.075, 95% CI −0.131 to 0.281, p=0.476). Although slightly fewer subjects who took NSAIDs reached remission [odds ratio (OR) 0.80, 95% CI 0.49–1.31, p=0.383], this non-significant effect was reversed after controlling for age, sex, baseline severity and recruitment centre effects (OR 1.04, 95% CI 0.61–1.77, p=0.882).


NSAIDs are unlikely to affect the efficacy of SRI or other antidepressants. Concurrent use of NSAIDs and antidepressants does not need to be avoided.


Corresponding author

*Address for correspondence: Dr R. Uher, P080, SGDP, Institute of Psychiatry, 16 De Crespigny Park, SE5 8AF, London, UK. (Email:


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BMA/RPS (2008). British Medical Association & Royal Pharmaceutical Society of Great Britain. British National Formulary (BNF) 55 – March 2008. British Medical Journal Publishing Group and Pharmaceutical Press: London, UK.
de Jong, JC, van den Berg, PB, Tobi, H, de Jong-van den Berg, LT (2003). Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse effects. British Journal of Clinical Pharmacology 55, 591595.
Fountoulakis, KN, Moller, HJ (2011). Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data. International Journal of Neuropsychopharmacology 14, 405412.
Frank, E, Prien, RF, Jarrett, RB, Keller, MB, Kupfer, DJ, Lavori, PW, Rush, AJ, Weissman, MM (1991). Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Archives of General Psychiatry 48, 851855.
Gu, Q, Dillon, CF, Burt, VL (2010). Prescription drug use continues to increase: U.S. prescription drug data for 2007–2008. NCHS data brief, no 42. National Center for Health Statistics: Hyattsville, MD.
Gueorguieva, R, Krystal, JH (2004). Move over ANOVA: progress in analyzing repeated-measures data and its reflection in papers published in the Archives of General Psychiatry. Archives of General Psychiatry 61, 310317.
Hayley, S (2011). Toward an anti-inflammatory strategy for depression. Frontiers in Behavioral Neuroscience 5, 19.
Lane, P (2008). Handling drop-out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches. Pharmaceutical Statistics 7, 93–106.
Leuchter, AF, Husain, MM, Cook, IA, Trivedi, MH, Wisniewski, SR, Gilmer, WS, Luther, JF, Fava, M, Rush, AJ (2010). Painful physical symptoms and treatment outcome in major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve Depression) report. Psychological Medicine 40, 239251.
Li, M, Soczynska, JK, Kennedy, SH (2011). Inflammatory biomarkers in depression: an opportunity for novel therapeutic interventions. Current Psychiatry Reports 13, 316320.
Loke, YK, Trivedi, AN, Singh, S (2008). Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Alimentary Pharmacology and Therapeutics 27, 3140.
Miller, AH, Maletic, V, Raison, CL (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732741.
Moller, HJ (2009). Standardised rating scales in psychiatry: methodological basis, their possibilities and limitations and descriptions of important rating scales. World Journal of Biological Psychiatry 10, 6–26.
NICE (2004). Depression: Management of Depression in Primary and Secondary Care, 1st edn. National Institute for Clinical Excellence (NICE), Department of Health, UK: London, UK.
Uher, R, Dernovsek, MZ, Mors, O, Hauser, J, Souery, D, Zobel, A, Maier, W, Henigsberg, N, Kalember, P, Rietschel, M, Placentino, A, Mendlewicz, J, Aitchison, KJ, McGuffin, P, Farmer, A (2011). Melancholic, atypical and anxious depression subtypes and outcome of treatment with escitalopram and nortriptyline. Journal of Affective Disorders 132, 112120.
Uher, R, Farmer, A, Maier, W, Rietschel, M, Hauser, J, Marusic, A, Mors, O, Elkin, A, Williamson, RJ, Schmael, C, Henigsberg, N, Perez, J, Mendlewicz, J, Janzing, JG, Zobel, A, Skibinska, M, Kozel, D, Stamp, AS, Bajs, M, Placentino, A, Barreto, M, McGuffin, P, Aitchison, KJ (2008). Measuring depression: comparison and integration of three scales in the GENDEP study. Psychological Medicine 38, 289300.
Uher, R, Maier, W, Hauser, J, Marusic, A, Schmael, C, Mors, O, Henigsberg, N, Souery, D, Placentino, A, Rietschel, M, Zobel, A, Dmitrzak-Weglarz, M, Petrovic, A, Jorgensen, L, Kalember, P, Giovannini, C, Barreto, M, Elkin, A, Landau, S, Farmer, A, Aitchison, KJ, McGuffin, P (2009 a). Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. British Journal of Psychiatry 194, 252259.
Uher, R, Mors, O, Hauser, J, Rietschel, M, Maier, W, Kozel, D, Henigsberg, N, Souery, D, Placentino, A, Perroud, N, Dernovsek, MZ, Strohmaier, J, Larsen, ER, Zobel, A, Leszczynska-Rodziewicz, A, Kalember, P, Pedrini, L, Linotte, S, Gunasinghe, C, Aitchison, KJ, McGuffin, P, Farmer, A (2009 b). Body weight as a predictor of antidepressant efficacy in the GENDEP project. Journal of Affective Disorders 118, 147154.
Uher, R, Muthen, B, Souery, D, Mors, O, Jaracz, J, Placentino, A, Petrovic, A, Zobel, A, Henigsberg, N, Rietschel, M, Aitchison, KJ, Farmer, A, McGuffin, P (2010). Trajectories of change in depression severity during treatment with antidepressants. Psychological Medicine 40, 13671377.
Vandraas, KF, Spigset, O, Mahic, M, Slordal, L (2010). Non-steroidal anti-inflammatory drugs: use and co-treatment with potentially interacting medications in the elderly. European Journal of Clinical Pharmacology 66, 823829.
Warner-Schmidt, JL, Vanover, KE, Chen, EY, Marshall, JJ, Greengard, P (2011). Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proceedings of the National Academy of Sciences USA 108, 92629267.
Wing, JK, Sartorius, N, Ustin, TB (1998). Diagnosis and Clinical Measurement in Psychiatry. A Reference Manual for SCAN. World Health Organization: Geneva.


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Non-steroidal anti-inflammatory drugs and efficacy of antidepressants in major depressive disorder

  • R. Uher (a1) (a2), S. Carver (a1), R. A. Power (a1), O. Mors (a3), W. Maier (a4), M. Rietschel (a5), J. Hauser (a6), M. Z. Dernovsek (a7), N. Henigsberg (a8), D. Souery (a9), A. Placentino (a10), A. Farmer (a1) and P. McGuffin (a1)...


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