Hostname: page-component-cd9895bd7-dk4vv Total loading time: 0 Render date: 2024-12-26T21:39:51.303Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  06 March 2012

R. Uher ,
S. Carver ,
R. A. Power ,
O. Mors ,
W. Maier ,
M. Rietschel ,
J. Hauser ,
M. Z. Dernovsek ,
N. Henigsberg  and
D. Souery
...Show all authors
R. Uher*
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK Department of Psychiatry, Dalhousie University, Halifax, NS, Canada
S. Carver
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
R. A. Power
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
O. Mors
Affiliation:
Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Germany
M. Rietschel
Affiliation:
Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Mannheim, Germany
J. Hauser
Affiliation:
Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Poland
M. Z. Dernovsek
Affiliation:
University Psychiatric Clinic, Ljubljana, Slovenia
N. Henigsberg
Affiliation:
Croatian Institute for Brain Research, Medical School, University of Zagreb, Croatia
D. Souery
Affiliation:
Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel – Centre Européen de Psychologie Médicale, Belgium
A. Placentino
Affiliation:
Psychiatric Unit (UOP 23), Department of Mental Health, Spedali Civili Hospital of Brescia, Italy; Biological Psychiatry Unit, IRCCS-FBF, Brescia; Faculty of Psychology, University of Milano-Bicocca, Italy
A. Farmer
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
P. McGuffin
Affiliation:
MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
*
*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)
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Antidepressant medicationdrug interactionsinflammationmajor depressive disordernon-steroidal anti-inflammatory drugsoutcome prediction
Type
Original Articles
Information
Psychological Medicine , Volume 42 , Issue 10 , October 2012 , pp. 2027 - 2035
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

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.Google Scholar
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, 591–595.CrossRefGoogle ScholarPubMed
Fountoulakis, KN, Moller, HJ (2011). Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data. International Journal of Neuropsychopharmacology 14, 405–412.CrossRefGoogle ScholarPubMed
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, 851–855.CrossRefGoogle ScholarPubMed
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.Google Scholar
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, 310–317.CrossRefGoogle ScholarPubMed
Hayley, S (2011). Toward an anti-inflammatory strategy for depression. Frontiers in Behavioral Neuroscience 5, 19.CrossRefGoogle ScholarPubMed
Lane, P (2008). Handling drop-out in longitudinal clinical trials: a comparison of the LOCF and MMRM approaches. Pharmaceutical Statistics 7, 93–106.CrossRefGoogle ScholarPubMed
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, 239–251.CrossRefGoogle Scholar
Li, M, Soczynska, JK, Kennedy, SH (2011). Inflammatory biomarkers in depression: an opportunity for novel therapeutic interventions. Current Psychiatry Reports 13, 316–320.CrossRefGoogle ScholarPubMed
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, 31–40.CrossRefGoogle ScholarPubMed
Miller, AH, Maletic, V, Raison, CL (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732–741.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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, 112–120.CrossRefGoogle ScholarPubMed
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, 289–300.CrossRefGoogle ScholarPubMed
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, 252–259.CrossRefGoogle ScholarPubMed
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, 147–154.CrossRefGoogle ScholarPubMed
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, 1367–1377.CrossRefGoogle ScholarPubMed
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, 823–829.CrossRefGoogle ScholarPubMed
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, 9262–9267.CrossRefGoogle ScholarPubMed
Wing, JK, Sartorius, N, Ustin, TB (1998). Diagnosis and Clinical Measurement in Psychiatry. A Reference Manual for SCAN. World Health Organization: Geneva.CrossRefGoogle Scholar