Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Systematic Reviews
Published in: Systematic Reviews 1/2021

Open Access 01-12-2021 | Antidepressant Drugs | Research

Efficacy, acceptability, and safety of antidepressants for low back pain: a systematic review and meta-analysis

Authors: Michael C. Ferraro, Matthew K. Bagg, Michael A. Wewege, Aidan G. Cashin, Hayley B. Leake, Rodrigo R. N. Rizzo, Matthew D. Jones, Sylvia M. Gustin, Richard Day, Colleen K. Loo, James H. McAuley

Published in: Systematic Reviews | Issue 1/2021

Login to get access

Abstract

Background

Antidepressant medicines are used to manage symptoms of low back pain. The efficacy, acceptability, and safety of antidepressant medicines for low back pain (LBP) are not clear. We aimed to evaluate the efficacy, acceptability, and safety of antidepressant medicines for LBP.

Methods

We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.​gov, the EU Clinical Trials Register, and the WHO International Clinical Trial Registry Platform from inception to May 2020. We included published and trial registry reports of RCTs that allocated adult participants with LBP to receive an antidepressant medicine or a placebo medicine. Pairs of authors independently extracted data in duplicate. We extracted participant characteristics, study sample size, outcome values, and measures of variance for each outcome. We data using random-effects meta-analysis models and calculated estimates of effects and heterogeneity for each outcome. We formed judgments of confidence in the evidence in accordance with GRADE. We report our findings in accordance with the PRISMA statement. We prespecified all outcomes in a prospectively registered protocol. The primary outcomes were pain intensity and acceptability. We measured pain intensity at end-of-treatment on a 0–100 point scale and considered 10 points the minimal clinically important difference. We defined acceptability as the odds of stopping treatment for any reason.

Results

We included 23 RCTs in this review. Data were available for pain in 17 trials and acceptability in 14 trials. Treatment with antidepressants decreased pain intensity by 4.33  points (95% CI − 6.15 to − 2.50) on a 0–100 scale, compared to placebo. Treatment with antidepressants increased the odds of stopping treatment for any reason (OR 1.27 [95% CI 1.03 to 1.56]), compared to placebo.

Conclusions

Treatment of LBP with antidepressants is associated with small reductions in pain intensity and increased odds of stopping treatment for any reason, compared to placebo. The effect on pain is not clinically important. The effect on acceptability warrants consideration. These findings provide Level I evidence to guide clinicians in their use of antidepressants to treat LBP.

Trial registration

We prospectively registered the protocol for this systematic review on PROSPERO (CRD42020149275).
Appendix
Available only for authorised users
Literature
1.
James SL, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1789–858.CrossRef
2.
Gore M, Tai KS, Sadosky A, Leslie D, Stacey BR. Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings. Pain Pract. 2012;12(7):550–60.PubMedCrossRef
3.
Hart OR, Uden RM, McMullan JE, Ritchie MS, Williams TD, Smith BH. A study of National Health Service management of chronic osteoarthritis and low back pain. Prim Health Care Res Dev. 2015;16(02):157–66.PubMedCrossRef
4.
Piccoliori G, Engl A, Gatterer D, Sessa E, in der Schmitten J, Abholz H-H. Management of low back pain in general practice – is it of acceptable quality: an observational study among 25 general practices in South Tyrol (Italy). BMC Fam Pract. 2013;14(1):148.PubMedPubMedCentralCrossRef
5.
Ivanova JI, Birnbaum HG, Schiller M, Kantor E, Johnstone BM, Swindle RW. Real-world practice patterns, health-care utilization, and costs in patients with low back pain: the long road to guideline-concordant care. Spine J. 2011;11(7):622–32.PubMedCrossRef
6.
Williams CM, Maher CG, Hancock MJ, McAuley JH, McLachlan AJ, Britt H, et al. Low back pain and best practice care. Arch Intern Med. 2010;170(3):271.PubMedCrossRef
7.
Bishop P, Wing P. Compliance with clinical practice guidelines in family physicians managing worker’s compensation board patients with acute lower back pain. Spine J. 2003;3(6):442–50.PubMedCrossRef
8.
Almeida M, Saragiotto B, Richards B, Maher CG. Primary care management of non-specific low back pain: key messages from recent clinical guidelines. Med J Aust. 2018;208(6):272–5.PubMedCrossRef
9.
10.
Wambeke P, Desomer A, Ailliet L, Berquin A, Demoulin C, Depreitere B, et al. Low back pain and radicular pain: assessment and management. Belgian Health Care Knowledge Centre (KCE). 2017.
11.
Qaseem A, Wilt TJ, McLean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American college of physicians. Ann Intern Med. 2017;166(7):514.PubMedCrossRef
12.
Shmagel A, Ngo L, Ensrud K, Foley R. Prescription medication use among community-based U.S. adults with chronic low back pain: a cross-sectional population based study. J Pain. 2018;19(10):1104–12.PubMedPubMedCentralCrossRef
13.
Thackeray A, Hess R, Dorius J, Brodke D, Fritz J. Relationship of opioid prescriptions to physical therapy referral and participation for medicaid patients with new-onset low back pain. J Am Board Fam Med. 2017;30(6):784–94.PubMedCrossRef
14.
Mathieson S, Valenti L, Maher CG, Britt H, Li Q, McLachlan AJ, et al. Worsening trends in analgesics recommended for spinal pain in primary care. Eur Spine J. 2018;27(5):1136–45.PubMedCrossRef
15.
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391(10128):1357–66.PubMedPubMedCentralCrossRef
16.
Harmer CJ, Duman RS, Cowen PJ. How do antidepressants work? New perspectives for refining future treatment approaches. The Lancet Psychiatry. 2017;4(5):409–18.PubMedPubMedCentralCrossRef
17.
Cohen SP, Abdi S. New developments in the use of tricyclic antidepressants for the management of pain. Curr Opin Anaesthesiol. 2001;14(5):505–11.PubMedCrossRef
18.
Koes BW, Backes D, Bindels PJE. Pharmacotherapy for chronic non-specific low back pain: current and future options. Expert Opin Pharmacother. 2018;19(6):537–45.PubMedCrossRef
19.
20.
Salerno SM, Browning R, Jackson JL. The effect of antidepressant treatment on chronic back pain. Arch Intern Med. 2002;162(1):19.PubMedCrossRef
21.
Staiger TO, Gaster B, Sullivan MD, A Deyo R. Systematic review of antidepressants in the treatment of chronic low back pain. Spine. 2003;28(22):2540–5.PubMedCrossRef
22.
Schnitzer TJ, Ferraro A, Hunsche E, Kong SX. 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(1):72–95.PubMedCrossRef
23.
Urquhart DM, Hoving JL, Assendelft WJ, Roland M, van Tulder MW. Antidepressants for non-specific low back pain. Cochrane Database Syst Rev. 2008;44(8):085201.
24.
Ferraro MC, Bagg MK, Folly de Campos T, McAuley JH. RADICAL: Systematic review of anti-depressant medicines if considered analgesics for low back pain. 2019. https://​osf.​io/​6gurb/​
25.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.PubMedPubMedCentralCrossRef
26.
Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009;373(9665):746–58.PubMedCrossRef
27.
28.
Bagg MK, McLachlan AJ, Maher CG, Kamper SJ, Williams CM, Henschke N, et al. Paracetamol, NSAIDS and opioid analgesics for chronic low back pain: a network meta-analysis. Cochrane Database Syst Rev. 2018(6):CD013045.
29.
Bagg MK, O’Hagan E, Zahara P, Wand BM, Hübscher M, Moseley GL, et al. Systematic reviews that include only published data may overestimate the effectiveness of analgesic medicines for low back pain: a systematic review and meta-analysis. J Clin Epidemiol. 2020;124:149-159.
30.
Dionne CE, Dunn KM, Croft PR, Nachemson AL, Buchbinder R, Walker BF, et al. A consensus approach toward the standardization of back pain definitions for use in prevalence studies. Spine. 2008;33(1):95–103.PubMedCrossRef
31.
32.
33.
34.
35.
36.
37.
Higgins J, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0 (updated March 2011). Cochrane Collaboration; 2011.
38.
Furlan AD, Malmivaara A, Chou R, Maher CG, Deyo RA, Schoene M, et al. 2015 updated method guideline for systematic reviews in the cochrane back and neck group. Spine. 2015;40(21):1660–73.PubMedCrossRef
39.
Furukawa TA, Salanti G, Atkinson LZ, Leucht S, Ruhe HG, Turner EH, et al. Comparative efficacy and acceptability of first-generation and second-generation antidepressants in the acute treatment of major depression: protocol for a network meta-analysis. BMJ Open. 2016;6(7):e010919.PubMedPubMedCentralCrossRef
40.
Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14(1):135.PubMedPubMedCentralCrossRef
41.
Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., Cochrane Handbook for Systematic Reviews of Interventions Version 6.0. Wiley; 2019.CrossRef
42.
Busse JW, Bartlett SJ, Dougados M, Johnston BC, Guyatt GH, Kirwan JR, et al. Optimal strategies for reporting pain in clinical trials and systematic reviews: recommendations from an OMERACT 12 workshop. J Rheumatol. 2015;42(10):1962–70.PubMedCrossRef
43.
44.
Viechtbauer W. Conducting meta-analyses in R with the metafor package. J Stat Softw. 2010;36(3):1–48.CrossRef
45.
46.
StataCorp LLC. Stata Statistical Software. College Station, TX; 2019.
47.
Ferreira ML, Herbert RD, Crowther MJ, Verhagen A, Sutton AJ. When is a further clinical trial justified? BMJ. 2012;345:e5913.PubMedCrossRef
48.
Langan D, Higgins JPT, Gregory W, Sutton AJ. Graphical augmentations to the funnel plot assess the impact of additional evidence on a meta-analysis. J Clin Epidemiol. 2012;65(5):511–9.PubMedCrossRef
49.
Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.PubMedPubMedCentralCrossRef
50.
Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, et al. Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ. 2011;343:d4002.PubMedCrossRef
51.
Alcoff J, Jones E, Rust P, Newman R. Controlled trial of imipramine for chronic low back pain. J Fam Pract. 1982;14(5):841–6.PubMed
52.
Atkinson JH, Slater MA, Capparelli EV, Wallace MS, Zisook S, Abramson I, et al. Efficacy of noradrenergic and serotonergic antidepressants in chronic back pain. J Clin Psychopharmacol. 2007;27(2):135–42.PubMedCrossRef
53.
Konno S, Oda N, Ochiai T, Alev L. Randomized, double-blind, placebo-controlled phase III trial of duloxetine monotherapy in Japanese patients with chronic low back pain. Spine. 2016;41(22):1709–17.PubMedPubMedCentralCrossRef
54.
Pheasant H, Bursk A, Goldfarb J, Azen SP, Weiss JN, Borelli L. Amitriptyline and chronic low-back pain: a randomized double-blind crossover study. Spine. 1983;8(5):552–7.PubMedCrossRef
55.
Schliessbach J, Siegenthaler A, Bütikofer L, Limacher A, Juni P, Vuilleumier PH, et al. Effect of single-dose imipramine on chronic low-back and experimental pain. A randomized controlled trial. PLoS One. 2018;13(5):e0195776.PubMedPubMedCentralCrossRef
56.
Schukro RP, Oehmke MJ, Geroldinger A, Heinze G, Kress H-G, Pramhas S. Efficacy of duloxetine in chronic low back pain with a neuropathic component. Anesthesiology. 2016;124(1):150–8.PubMedCrossRef
57.
Skljarevski V, Desaiah D, Liu-Seifert H, Zhang Q, Chappell AS, Detke MJ, et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine. 2010;35(13):E578–85.PubMedCrossRef
58.
Skljarevski V, Ossanna M, Liu-Seifert H, Zhang Q, Chappell A, Iyengar S, et al. A double-blind, randomized trial of duloxetine versus placebo in the management of chronic low back pain. Eur J Neurol. 2009;16(9):1041–8.PubMedCrossRef
59.
Skljarevski V, Zhang S, Desaiah D, Alaka KJ, Palacios S, Miazgowski T, et al. Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial. J Pain. 2010;11(12):1282–90.PubMedCrossRef
60.
Treves R, Montane De La Roque P, Dumond JJ, Bertin P, Arnaud M, Desproges-Gotteron R. Prospective study of the analgesic action of clomipramine versus placebo in refractory low back pain and sciatica (68 cases). Rev Rhum Mal Osteoartic. 1991;58(7):549–52.PubMed
61.
Urquhart DM, Wluka AE, van Tulder M, Heritier S, Forbes A, Fong C, et al. Efficacy of low-dose amitriptyline for chronic low back pain. JAMA Intern Med. 2018;178(11):1474–81.PubMedPubMedCentralCrossRef
62.
Atkinson JH, Slater MA, Wahlgren DR, Williams RA, Zisook S, Pruitt SD, et al. Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity. Pain. 1999;83(2):137–45.PubMedCrossRef
63.
Atkinson JH, Slater MA, Williams RA, Zisook S, Patterson TL, Grant I, et al. A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain. Pain. 1998;76(3):287–96.PubMedCrossRef
64.
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(6):490–9.PubMedCrossRef
65.
Goodkin K, Gullion CM, Agras WS. A randomized, double-blind, placebo-controlled trial of trazodone hydrochloride in chronic low back pain syndrome. J Clin Psychopharmacol. 1990;10(4):269–78.PubMedCrossRef
66.
Gould HM, Atkinson JH, Chircop-Rollick T, DʼAndrea J, Garfin S, Patel SM, et al. A randomized placebo-controlled trial of desipramine, cognitive behavioral therapy, and active placebo therapy for low back pain. Pain. 2020;161(6):1341–9.PubMedCrossRef
67.
Jenkins DG, Ebbutt AF, Evans CD. Tofranil in the treatment of low back pain. J Int Med Res. 1976;4(2):28–40.PubMed
68.
Johnson K, Chatterjee N, Noor N, Crowell A, McCue R, Mackey S. Effects of duloxetine and placebo in patients with chronic low back pain. J Pain. 2011;12(4):P49.CrossRef
69.
Katz J, Pennella-Vaughan J, Hetzel RD, Kanazi GE, Dworkin RH. A randomized, placebo-controlled trial of bupropion sustained release in chronic low back pain. J Pain. 2005;6(10):656–61.PubMedCrossRef
70.
Veroniki AA, Jackson D, Viechtbauer W, Bender R, Bowden J, Knapp G, et al. Methods to estimate the between-study variance and its uncertainty in meta-analysis. Res Synth Methods. 2016;7(1):55–79.PubMedCrossRef
71.
Chou R, Deyo R, Friedly J, Skelly A, Weimer M, Fu R, et al. Systemic pharmacologic therapies for low back pain: a systematic review for an American College of Physicians clinical practice guideline. Ann Intern Med. 2017;166(7):480.PubMedCrossRef
72.
Oliveira CB, Maher CG, Pinto RZ, Traeger AC, Lin C-WC, Chenot J-F, et al. Clinical practice guidelines for the management of non-specific low back pain in primary care: an updated overview. Eur Spine J. 2018;27(11):2791–803.PubMedCrossRef
73.
Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, et al. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9(2):105–21.PubMedCrossRef
74.
Lee H, Lamb SE, Bagg MK, Toomey E, Cashin AG, Moseley GL. Reproducible and replicable pain research: a critical review. Pain. 2018;159(9):1683–9.PubMedCrossRef
75.
Baudard M, Yavchitz A, Ravaud P, Perrodeau E, Boutron I. Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses. BMJ. 2017;356:j448.PubMedPubMedCentralCrossRef
76.
Hart B, Lundh A, Bero L. Effect of reporting bias on meta-analyses of drug trials: reanalysis of meta-analyses. BMJ. 2012;344:d7202.PubMedCrossRef
Metadata
Title
Efficacy, acceptability, and safety of antidepressants for low back pain: a systematic review and meta-analysis
Authors
Michael C. Ferraro
Matthew K. Bagg
Michael A. Wewege
Aidan G. Cashin
Hayley B. Leake
Rodrigo R. N. Rizzo
Matthew D. Jones
Sylvia M. Gustin
Richard Day
Colleen K. Loo
James H. McAuley
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Systematic Reviews / Issue 1/2021
Electronic ISSN: 2046-4053
DOI
https://doi.org/10.1186/s13643-021-01599-4

Other articles of this Issue 1/2021

Systematic Reviews 1/2021 Go to the issue

Letter

The effects of meditation on length of telomeres in healthy individuals: a systematic review

Protocol

Psychometric properties of medication adherence instruments in cardiovascular diseases and type 2 diabetes mellitus: systematic review protocol

Protocol

Early pregnancy loss incidence in high-income settings: a protocol for a systematic review and meta-analysis

Protocol

Early intervention for young children with autism spectrum disorder: protocol for a scoping review of economic evaluations

Protocol

Exercise interventions for older adults with Alzheimer’s disease: a systematic review and meta-analysis protocol

Protocol

Therapeutic potential of pluripotent stem cell-derived dopaminergic progenitors in Parkinson’s disease: a systematic review protocol