Skip to main content
×
×
Home

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)...
Abstract
Background

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.

Method

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.

Results

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).

Conclusions

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

Copyright
Corresponding author
*Address for correspondence: Dr R. Uher, P080, SGDP, Institute of Psychiatry, 16 De Crespigny Park, SE5 8AF, London, UK. (Email: rudolf.uher@kcl.ac.uk)
References
Hide All
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.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 9
Total number of PDF views: 57 *
Loading metrics...

Abstract views

Total abstract views: 400 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 16th December 2017. This data will be updated every 24 hours.