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Published in: Trials 1/2016

Open Access 01-12-2016 | Study protocol

Is low-dose amitriptyline effective in the management of chronic low back pain? Study protocol for a randomised controlled trial

Authors: Donna M. Urquhart, Anita E. Wluka, Malcolm R. Sim, Maurits van Tulder, Andrew Forbes, Stephen J. Gibson, Carolyn Arnold, Chris Fong, Shane N. Anthony, Flavia M. Cicuttini

Published in: Trials | Issue 1/2016

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Abstract

Background

Low back pain is a major clinical and public health problem, with limited evidence-based treatments. Low-dose antidepressants are commonly used to treat pain in chronic low back pain. However, their efficacy is unproven. The aim of this pragmatic, double-blind, randomised, placebo-controlled trial is to determine whether low-dose amitriptyline (an antidepressant) is more effective than placebo in reducing pain in individuals with chronic low back pain.

Methods/design

One hundred and fifty individuals with chronic low back pain will be recruited through hospital and private medical and allied health clinics, advertising in local media and posting of flyers in community locations. They will be randomly allocated to receive either low-dose amitriptyline (25 mg) or an active placebo (benztropine mesylate, 1 mg) for 6 months. The primary outcome measure of pain intensity will be assessed at baseline, 3 and 6 months using validated questionnaires. Secondary measures of self-reported low back disability, work absence and hindrance in the performance of paid/unpaid work will also be examined. Intention-to-treat analyses will be performed.

Discussion

This pragmatic, double-blind, randomised, placebo-controlled trial will provide evidence regarding the effectiveness of low-dose antidepressants compared with placebo in reducing pain, disability, work absenteeism and hindrance in work performance in individuals with chronic low back pain. This trial has major public health and clinical importance as it has the potential to provide an effective approach to the management of chronic low back pain.

Trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12612000131​853; registered on 30 January 2012.
Appendix
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Literature
1.
Burton A, Balagué F, Cardon G, Eriksen H, Henrotin Y, Lahad A, Leclerc A, Müller G, van der Beek A. COST B13 Working Group on Guidelines for Prevention in Low Back Pain. Chapter 2: European guidelines for prevention in low back pain. Eur Spine J. 2006;15:S136–68.CrossRefPubMedPubMedCentral
2.
Vos T, Flaxman A, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon J, et al. Years lived with disability for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–96.CrossRefPubMed
3.
Walker B, Muller R, Grant W. Low back pain in Australian adults: the economic burden. Asia Pac J Public Health. 2003;15:79–87.CrossRefPubMed
4.
Luo X, Pietrobon R, Sun S, Liu G, Hey L. Estimates and patterns of direct health care expenditures among individuals with back pain in the United States. Spine. 2004;29:79–86.CrossRefPubMed
5.
Olfson M, Marcus S. National patterns in antidepressant medication treatment. Arch Gen Psychiatry. 2009;66:848–56.CrossRefPubMed
6.
Micó J, Ardid D, Berrocoso E, Eschalier A. Antidepressants and pain. Trends Pharmacol Sci. 2006;27:348–54.CrossRefPubMed
7.
Goldenberg D. Pharmacological treatment of fibromyalgia and other chronic musculoskeletal pain. Baillieres Best Pract Res Clin Rheumatol. 2007;21:499–511.CrossRef
8.
Roussel N, Nijs J, Meeus M, Mylius V, Fayt C, Oostendorp R. Central sensitization and altered central pain processing in chronic low back pain: fact or myth? Clin J Pain. 2013;29:625–38.CrossRefPubMed
9.
Cohen S, Abdi S. New development in the use of antidepressants for the management of pain. Curr Opin Anaesthesiol. 2001;14:505–11.CrossRefPubMed
10.
McQuay H, Tramer M, Nye B, Carroll D, Wiffen P, Moore R. A systematic review of antidepressants in neuropathic pain. Pain. 1996;68:217–27.CrossRefPubMed
11.
Salerno S, Browning R, Jackson J. The effect of antidepressant treatment on chronic back pain: a meta-analysis. Arch Intern Med. 2002;162:19–24.CrossRefPubMed
12.
Staiger T, Gaster B, Sullivan M, Deyo R. Systematic review of antidepressants in the treatment of chronic low back pain. Spine. 2003;28:2540–5.CrossRefPubMed
13.
Schnitzer T, Ferraro A, Hunsche E, Kong S. A comprehensive review of clinical trials on the efficacy and safety of drugs for the treatment of low back pain. J Pain Symptom Manage. 2004;28:72–95.CrossRefPubMed
14.
Urquhart DM1, Hoving JL, Assendelft WW, Roland M, van Tulder MW. Antidepressants for non-specific low back pain. Cochrane Database Syst Rev. 2008;(1):CD001703.
15.
Atkinson J, Slater M, Capparelli E, Wallace M, Zisook S, Abramson I, Matthews S, Garfin S. Efficacy of noradrenergic and serotonergic antidepressants in chronic back pain. J Clin Psychopharmacol. 2007;27:135–42.CrossRefPubMed
16.
Schulz K, Altman D, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMJ (Clinical research ed). 2010;340:c332.CrossRef
17.
18.
van Tulder M, Koes B, Bombardier C. Low back pain. Best Pract Res Clin Rheumatol. 2002;16:761–75.CrossRefPubMed
19.
19. Mant A, Rendle V, Hall W, Mitchell P, Montgomery W, McManus P, Hickie I. Making new choices about antidepressants in Australia: the long view 1975–2002 Med J Aust. 2004;181 S21-S24
20.
Sindrup S, Jensen T. Efficacy of pharmacologic treatments of neuropathic pain. Pain. 1999;83:389–400.CrossRefPubMed
21.
Koh W, Pande I, Samuels A, Jones S, Calin A. Low dose amitriptyline in ankylosing spondylitis: a short term, double blind, placebo controlled study. J Rheumatol. 1997;24:2158–61.PubMed
22.
Holroyd K, O’Donnell F, Stensland M, Lipchik G, Cordingley G, Carlson B. Management of chronic tension-type headache with tricyclic antidepressant medication, stress management therapy, and their combination: a randomized controlled trial. JAMA. 2001;285:2208–15.CrossRefPubMedPubMedCentral
23.
Watson C, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J. Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Pain. 2003;105:71–8.CrossRefPubMed
24.
Moulin D, Iezzi A, Amireh R, Sharpe W, Boyd D, Merskey H. Randomised trial of oral morphine for chronic non-cancer pain. Lancet. 1996;347:143–7.CrossRefPubMed
25.
Gracely R, Kwilosz D. The Descriptor Differential Scale: applying psychophysical principles to clinical pain assessment. Pain. 1988;35:279–88.CrossRefPubMed
26.
Roland M, Morris R. A study of the natural history of back pain. Part I: development of a reliable and sensitive measure of disability in low-back pain. Spine. 1983;8:141–4.CrossRefPubMed
27.
van Roijen L, Essink-Bot M, Koopmanschap M, Bonsel G, Rutten F. Labor and health status in economic evaluation of health care. The Health and Labor Questionnaire. Int J Technol Assess Health Care. 1996;12:405–15.CrossRefPubMed
28.
Dworkin RHTD, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J. IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. Pain. 2005;113:9–19.CrossRefPubMed
29.
Kind P. The EuroQol Instrument: an index of health-related quality of life. In: Spilker B, editor. Quality of life and pharmacoeconomics in clinical trials. Philadelphia: Lippincott-Raven; 1996. p. 191–201.
30.
Beck A, Steer R, Garbin M. Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psych Rev. 1988;8:77–100.CrossRef
31.
Crombez G, Vlaeyen J, Heuts P, Lysens R. Pain-related fear is more disabling than pain itself: evidence on the role of pain-related fear in chronic back pain disability. Pain. 1999;80:329–39.CrossRefPubMed
32.
Craig C, Marshall A, Sjostrom M, Bauman A, Booth M, Ainsworth B, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381–95.CrossRefPubMed
33.
Lingjaerde O, Ahlfors U, Bech P, Dencker S, Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand Suppl. 1987;334:1–100.CrossRefPubMed
34.
Dickens C, Jayson M, Sutton C, Creed F. The relationship between pain and depression in a trial using paroxetine in sufferers of chronic low back pain. Psychosomatics. 2000;41:490–9.CrossRefPubMed
35.
Doctor J, Slater M, Atkinson J. The Descriptor Differential Scale of Pain Intensity: an evaluation of item and scale properties. Pain. 1995;61(61):251–60.CrossRefPubMed
36.
Bombardier C, Hayden J, Beaton D. Minimal clinically important difference. Low back pain: outcome measures. J Rheumatol. 2001;28:431–8.PubMed
37.
Dionne C, Von Korff M, Koepsell T, Deyo R, Barlow W, Checkoway H. A comparison of pain, functional limitations, and work status indices as outcome measures in back pain research. Spine. 1999;24:2339–45.CrossRefPubMed
38.
Hernán M, Lanoy E, Costagliola D, Robins J. Comparison of dynamic treatment regimes via inverse probability weighting. Basic Clin Pharmacol Toxicol. 2006;98:237–42.CrossRefPubMed
39.
Jenkins D, Ebbutt A, Evans C. Tofranil in the treatment of low back pain. J Int Med Res. 1976;4:28–40.PubMed
40.
Goodkin K, Gullion C, Agras W. A randomized, double-blind, placebo-controlled trial of trazodone hydrochloride in chronic low back pain syndrome. J Clin Psychopharmacol. 1990;10:269–78.CrossRefPubMed
41.
Atkinson J, Slater M, Wahlgren D, Williams R, Zisook S, Pruitt S, Epping-Jordan J, Patterson T, Grant I, Abramson I, Garfin S. Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity. Pain. 1999;83:137–45.CrossRefPubMed
42.
Katz J, Pennella-Vaughan J, Hetzel R, Kanazi G, Dworkin R. A randomised, placebo-controlled trial of bupropion sustained release in chronic low back pain. J Pain. 2005;6:656–61.CrossRefPubMed
Metadata
Title
Is low-dose amitriptyline effective in the management of chronic low back pain? Study protocol for a randomised controlled trial
Authors
Donna M. Urquhart
Anita E. Wluka
Malcolm R. Sim
Maurits van Tulder
Andrew Forbes
Stephen J. Gibson
Carolyn Arnold
Chris Fong
Shane N. Anthony
Flavia M. Cicuttini
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Trials / Issue 1/2016
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-016-1637-1

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