Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Oct 21;10(10):CD012157.
doi: 10.1002/14651858.CD012157.pub2.

Antidepressants for hip and knee osteoarthritis

Alexandra A Leaney  1 , Jenna R Lyttle  1 , Julian Segan  1 , Donna M Urquhart  1 , Flavia M Cicuttini  1 , Louisa Chou  2 , Anita E Wluka  1
Affiliations

Antidepressants for hip and knee osteoarthritis

Alexandra A Leaney et al. Cochrane Database Syst Rev. .

Abstract

Background: Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has resulted in the investigation of medications affecting pain processing with central effects. Antidepressants contribute to pain management in other conditions where pain sensitisation is present.

Objectives: To assess the benefits and harms of antidepressants for the treatment of symptomatic knee and hip osteoarthritis in adults.

Search methods: We used standard, extensive Cochrane search methods. The latest search was January 2021.

Selection criteria: We included randomised controlled trials of adults with osteoarthritis that compared use of antidepressants to placebo or alternative comparator. We included trials that focused on efficacy (pain and function), treatment-related adverse effects and had documentation regarding discontinuation of participants. We excluded trials of less than six weeks of duration or had participants with concurrent mental health disorders.

Data collection and analysis: We used standard Cochrane methods. Major outcomes were pain; responder rate; physical function; quality of life; and proportion of participants who withdrew due to adverse events, experienced any adverse events or had serious adverse events. Minor outcomes were proportion meeting the OARSI (Osteoarthritis Research Society International) Response Criteria, radiographic joint structure changes and proportion of participants who dropped out of the study for any reason. We used GRADE to assess certainty of evidence.

Main results: Nine trials (2122 participants) met the inclusion criteria. Seven trials examined only knee osteoarthritis. Two also included participants with hip osteoarthritis. All trials compared antidepressants to placebo, with or without non-steroidal anti-inflammatory drugs. Trial sizes were 36 to 388 participants. Most participants were female, with mean ages of 54.5 to 65.9 years. Trial durations were 8 to 16 weeks. Six trials examined duloxetine. We combined data from nine trials in meta-analyses for knee and hip osteoarthritis. One trial was at low risk of bias in all domains. Five trials were at risk of attrition and reporting bias. High-certainty evidence found that antidepressants resulted in a clinically unimportant improvement in pain compared to placebo. Mean reduction in pain (0 to 10 scale, 0 = no pain) was 1.7 points with placebo and 2.3 points with antidepressants (mean difference (MD) -0.59, 95% confidence interval (CI) -0.88 to -0.31; 9 trials, 2122 participants). Clinical response was defined as achieving a 50% or greater reduction in 24-hour mean pain. High-certainty evidence demonstrated that 45% of participants receiving antidepressants had a clinical response compared to 28.6% receiving placebo (RR 1.55, 95% CI 1.32 to 1.82; 6 RCTs, 1904 participants). This corresponded to an absolute improvement in pain of 16% more responders with antidepressants (8.9% more to 26% more) and a number needed to treat for an additional beneficial effect (NNTB) of 6 (95% CI 4 to 11). High-certainty evidence showed that the mean improvement in function (on 0 to 100 Western Ontario and McMaster Universities Arthritis Index, 0 = best function) was 10.51 points with placebo and 16.16 points with antidepressants (MD -5.65 points, 95% CI -7.08 to -4.23; 6 RCTs, 1909 participants). This demonstrates a small, clinically unimportant response. Moderate-certainty evidence (downgraded for imprecision) showed that quality of life measured using the EuroQol 5-Dimension scale (-0.11 to 1.0, 1.0 = perfect health) improved by 0.07 points with placebo and 0.11 points with antidepressants (MD 0.04, 95% CI 0.01 to 0.07; 3 RCTs, 815 participants). This is clinically unimportant. High-certainty evidence showed that total adverse events increased in the antidepressant group (64%) compared to the placebo group (49%) (RR 1.27, 95% CI 1.15 to 1.41; 9 RCTs, 2102 participants). The number needed to treat for an additional harmful outcome (NNTH) was 7 (95% CI 5 to 11). Low-certainty evidence (downgraded twice for imprecision for very low numbers of events) found no evidence of a difference in serious adverse events between groups (RR 0.94, 95% CI 0.46 to 1.94; 9 RCTs, 2101 participants). The NNTH was 1000. Moderate-certainty evidence (downgraded for imprecision) showed that 11% of participants receiving antidepressants withdrew from trials due to an adverse event compared to 5% receiving placebo (RR 2.15, 95% CI 1.56 to 2.97; 6 RCTs, 1977 participants). The NNTH was 17 (95% CI 10 to 35).

Authors' conclusions: There is high-certainty evidence that use of antidepressants for knee osteoarthritis leads to a non-clinically important improvement in mean pain and function. However, a small number of people will have a 50% or greater important improvement in pain and function. This finding was consistent across all trials. Pain in osteoarthritis may be due to a variety of causes that differ between individuals. It may be that the cause of pain that responds to this therapy is only present in a small number of people. There is moderate-certainty evidence that antidepressants have a small positive effect on quality of life with heterogeneity between trials. High-certainty evidence indicates antidepressants result in more adverse events and moderate-certainty evidence indicates more withdrawal due to adverse events. There was little to no difference in serious adverse events (low-certainty evidence due to low numbers of events). This suggests that if antidepressants were being considered, there needs to be careful patient selection to optimise clinical benefit given the known propensity for adverse events with antidepressant use. Future trials should include alternative antidepressant agents or phenotyping of pain in people with osteoarthritis, or both.

Trial registration: ClinicalTrials.gov NCT01510457 NCT01558700 NCT02248480 NCT01931475 NCT04532684.

PubMed Disclaimer

Conflict of interest statement

AL: none.

JL: none.

JS: none.

DU: is a co‐investigator in a current ongoing study regarding amitriptyline in osteoarthritis (ACTRN12615000301561). They did not perform data extraction for this trial.

FC: is a co‐investigator in a current ongoing study regarding amitriptyline in osteoarthritis (ACTRN12615000301561). They did not perform data extraction for this trial.

LC: none.

AW: is the lead researcher in a current ongoing study regarding amitriptyline in osteoarthritis (ACTRN12615000301561). They did not perform data extraction for this trial. AW is currently a lead author on a systematic review and meta‐analysis on the prevalence of neuropathic‐like pain and central sensitisation in hip and knee osteoarthritis.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 1: Mean pain at 8–16 weeks
1.2
1.2. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 2: Responder rate: ≥ 50% reduction in pain
1.3
1.3. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 3: Physical function (WOMAC)
1.4
1.4. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 4: Mean change in quality of life at 10–14 weeks
1.5
1.5. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 5: Proportion of study withdrawals due to adverse effects
1.6
1.6. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 6: Total adverse events
1.7
1.7. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 7: Serious adverse events
1.8
1.8. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 8: OARSI responders
1.9
1.9. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 9: Radiographic joint structure changes
1.10
1.10. Analysis
Comparison 1: Antidepressants versus placebo in hip and knee osteoarthritis, Outcome 10: Total treatment withdrawals
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

References to studies included in this review

Chappell 2009b {published data only}
    1. Chappell AS, Desaiah D, Liu-Seifert H, Zhang S, Skljarevski V, Belenkov Y, et al. Duloxetine 60 to 120 mg once daily versus placebo in the treatment of patients with osteoarthritis knee pain. Pain Medicine 2009;10(1):250. [DOI: ]
    1. Chappell AS, Ossanna MJ, Liu-Seifert H, Iyengar S, Skljarevski V, Li L, et al. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial. Pain 2009;146(3):253-60. [DOI: ] - PubMed
Chappell 2011 {published data only}
    1. Chappell AS, Desaiah D, Liu-Seifert H, Zhang S, Skljarevski V, Belenkov Y, et al. A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Practice 2011;11(1):33-41. [DOI: ] - PubMed
    1. Micca JL, Risser RC, Ahl J, Wohlreich MM. The efficacy and safety of duloxetine treatment in older patients with osteoarthritis knee pain: a post hoc, subgroup analysis of data from 2 placebo-controlled trials. Arthritis and Rheumatism 2011;63(10 Suppl):1.
    1. Micca JL, Ruff D, Ahl J, Wohlreich MM. Safety and efficacy of duloxetine treatment in older and younger patients with osteoarthritis knee pain: a post hoc, subgroup analysis of two randomized, placebo-controlled trials. BMC Musculoskeletal Disorders 2013;14:137. [DOI: ] - PMC - PubMed
Frakes 2011 {published data only (unpublished sought but not used)}
    1. Frakes E, Risser R, Ball T, Hochberg M, Wohlreich M. Erratum: duloxetine added to nonsteroidal antiinflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial (Current Medical Research and Opinion (2011) 27:12 (1-12)). Current Medical Research and Opinion 2012;28(5):822. [DOI: ] - PubMed
    1. Frakes EP, Risser RC, Ball TD, Hochberg MC, Wohlreich MM. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis: results of a randomized, double-blind, placebo-controlled trial. [Erratum appears in Current Medical Research & Opinion 2012;28(5):822]. Current Medical Research & Opinion 2011;27(12):2361-72. [DOI: ] - PubMed
    1. Risser RC, Hochberg MC, Gaynor PJ, D'Souza DN, Frakes EP. Responsiveness of the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale in a trial of duloxetine for treatment of osteoarthritis knee pain. Osteoarthritis and Cartilage 2013;21(5):691-4. - PubMed
Hudson 2021 {published data only (unpublished sought but not used)}
    1. Hudson B, Toop L, Williman J, Hooper G, Mangin D, Alchin J, Thompson B, Stamp L. Nortriptyline in knee arthritis (Nortika): a randomised controlled double blind trial of nortriptyline for pain in knee osteoarthritis [abstract]. Arthritis & Rheumatology 2019;71(Suppl 10):2758.
    1. Hudson B, Williman JA, Stamp LK, Alchin JS, Hooper GJ, Mangin D, et al. Nortriptyline for pain in knee osteoarthritis in general practice: a double blind randomised controlled trial. British Journal of General Practise 2021;71(708):e538-46. - PMC - PubMed
    1. Hudson B, Williman JA, Stamp LK, Alchin JS, Hooper GJ, Mangin D, et al. Nortriptyline in knee osteoarthritis (NortIKA study): study protocol for a randomised controlled trial. Trials 2015;16:448. [DOI: 10.1186/s13063-015-0961-1] - DOI - PMC - PubMed
Mathur 2015 {published and unpublished data}
    1. Mathur S, Saracoglu M, Kuroda M, Graciosa J, Hirsch B, Kirsling A, et al. Functional testing and pre-to post pain measure outcomes in chronic knee osteoarthritis pain with milnacipran: interim analysis of a randomized, double-blind, placebo-controlled trial. Journal of Pain 2013;1:S66. [DOI: ]
Riesner 2008 {published data only (unpublished sought but not used)}
    1. Riesner HJ, Zeitler C, Schreiber H, Wild A. Additional treatment in chronic pain syndrome due to hip and knee arthritis with the selective serotonin reuptake inhibitor fluvoxamine (Fevarin). Zeitschrift fur Orthopadie & Unfallchirurgie 2008;146(6):742-6. [DOI: ] - PubMed
Tetreault 2016 {published data only}
    1. Tetreault P, Baliki M, Vachon-Presseau E, Yeasted RE, Schnitzer TJ, Apkarian AV. Cortical reorganization after duloxetine treatment-related pain decrease in knee osteoarthritis. Arthritis and Rheumatology 2014;66:S410-1. [DOI: ]
    1. Tetreault P, Mansour A, Vachon-Presseau E, Schnitzer TJ, Vania Apkarian A, Baliki MN. Brain connectivity predicts placebo response across chronic pain clinical trials. PLOS Biology 2016;14:10. - PMC - PubMed
Uchio 2018 {published data only}
    1. Eli Lilly and Company. An open label extension study of phase 3 trial of duloxetine in patients with osteoarthritis and knee pain. clinicaltrials.gov/ct2/show/NCT02335346 (first received 9 January 2015). [NCT02335346]
    1. Uchio Y, Enomoto H, Alev L, Kato Y, Ishihara H, Tsuji T, et al. A randomized, double-blind, placebo-controlled phase III trial of duloxetine in Japanese patients with knee pain due to osteoarthritis. Journal of Pain Research 2018;11:809-21. [PMID: ] - PMC - PubMed
Wang 2017 {published data only}
    1. Wang G, Bi L, Li X, Li Z, Zhao D, Chen J, et al. Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study. Osteoarthritis and Cartilage 2017;25(6):832-8. [DOI: 10.1016/j.joca.2016.12.025] - DOI - PubMed

References to studies excluded from this review

Alaka 2013 {published data only}
    1. Alaka K, Zhang Q, Ahl J, Boulay L, Skljarevski V. Safety of duloxetine for the treatment of older patients with osteoarthritis knee pain or chronic low back pain. Journal of Pain 2013;1:S61. [DOI: ]
Bellingham 2010 {published data only}
    1. Bellingham GA, Peng PW. Duloxetine: a review of its pharmacology and use in chronic pain management. Regional Anesthesia and Pain Medicine 2010;35(3):294-303. [DOI: ] - PubMed
Brown 2013 {published data only}
    1. Brown JP, Boulay LJ. Clinical experience with duloxetine in the management of chronic musculoskeletal pain. A focus on osteoarthritis of the knee. Therapeutic Advances in Musculoskeletal Disease 2013;5(6):291-304. [DOI: ] - PMC - PubMed
Brunton 2010 {published data only}
    1. Brunton S, Wang F, Edwards SB, Crucitti AS, Ossanna MJ, Walker DJ, et al. Profile of adverse events with duloxetine treatment: a pooled analysis of placebo-controlled studies. Drug Safety 2010;33(5):393-407. [DOI: ] - PubMed
Chen 2019 {published data only}
    1. Chen L, Gong M, Liu G, Xiang Z. Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta-analysis of randomized controlled trials. Internal Medicine Journal 2019;49(12):1514-523. - PubMed
Citrome 2012a {published data only}
    1. Citrome L, Weiss-Citrome A. Antidepressants and the relief of osteoarthritic pain – findings from a study examining adjunctive duloxetine. International Journal of Clinical Practice 2012;66(5):431-3. [DOI: ] - PubMed
Citrome 2012b {published data only}
    1. Citrome L, Weiss-Citrome A. A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and likelihood to be helped or harmed? Postgraduate Medicine 2012;124(1):83-93. [DOI: ] - PubMed
Driban 2012 {published data only}
    1. Driban JB, Lo GH, Eaton CB, Lapane KL, Nevitt M, Harvey WF, et al. Exploratory analysis of osteoarthritis progression among medication users: data from the osteoarthritis initiative. Osteoarthritis and Cartilage 2012;20:S287-8. [DOI: ] - PMC - PubMed
Ferreira 2021 {published data only}
    1. Ferreira GE, McLachlan AJ, Lin CW, Zadro JR, Abdel-Shaheed C, O'Keeffe M, et al. Efficacy and safety of antidepressants for the treatment of back pain and osteoarthritis: systematic review and meta-analysis. BMJ 2021;372:m4825. [DOI: ] - PMC - PubMed
Fishbain 2000 {published data only}
    1. Fishbain D. Evidence-based data on pain relief with antidepressants (structured abstract). Annals of Medicine 2000;32(5):305-16. - PubMed
Gaynor 2010 {published data only}
    1. Gaynor PJ, Hochberg MC, Risser R, Wohlreich M, Hanna S. Outcomes in osteoarthritis (OA): analysis of pooled data from randomized placebo-controlled clinical trials of duloxetine in patients with knee OA. Pain Medicine 2010;11(2):288-9. [DOI: ]
Gaynor 2013 {published data only}
    1. Gaynor PJ, Liu P, Weller MA, Wohlreich MM. Comparison of safety outcomes among Caucasian, Hispanic, Black, and Asian patients in duloxetine studies of chronic painful conditions. Current Medical Research and Opinion 2013;29(5):549-60. [DOI: ] - PubMed
Hochberg 2012 {published data only}
    1. Hochberg MC, Peng L, Ahl J, Zhang S, Skljarevski V, Gaynor P, et al. Duloxetine as treatment for knee pain in patients with osteoarthritis who regularly use nonsteroidal anti-inflammatory drugs (NSAIDS): a post hoc analysis of two randomized, placebo-controlled trials. Osteoarthritis and Cartilage 2011;19:S146-7.
    1. Hochberg MC, Wohlreich M, Gaynor P, Hanna S, Risser R. Clinically relevant outcomes based on analysis of pooled data from 2 trials of duloxetine in patients with knee osteoarthritis. Journal of Rheumatology 2012;39(2):352-8. [DOI: ] - PubMed
Lin 2003 {published data only}
    1. Lin EH, Katon W, Korff M, Tang L, Williams JW Jr, Kroenke K, et al. Effect of improving depression care on pain and functional outcomes among older adults with arthritis: a randomized controlled trial. JAMA 2003;290(18):2428-34. [DOI: ] - PubMed
Moore 2014 {published data only}
    1. Moore RA, Cai N, Skljarevski V, Tolle TR. Duloxetine use in chronic painful conditions – individual patient data responder analysis. European Journal of Pain 2014;18(1):67-75. [DOI: ] - PMC - PubMed
Myers 2012 {published data only}
    1. Myers JA, Wielage RC, Han B, Price K, Gahn JC, Paget MA, et al. The efficacy of duloxetine, non-steroidal anti-inflammatory drugs, and opioids in osteoarthritis: a meta-analysis. Value in Health 2012;15(4):A33. [DOI: ] - PMC - PubMed
Osani 2019 {published data only}
    1. Osani MC, Bannuru MC. Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis. Korean Journal of Internal Medicine 2019;34(5):966-73. - PMC - PubMed
Peng 2013 {published data only}
    1. Peng X, Wu N, Chen SY, Yu X, Andrews JS, Novick D. Utilization of duloxetine and celecoxib in osteoarthritis patients. Current Medical Research & Opinion 2013;29(9):1161-9. [DOI: ] - PubMed
Pergolizzi 2013 {published data only}
    1. Pergolizzi JV, Raffa RB, Taylor R, Rodriguez G, Nalamachu S, Langley P. A review of duloxetine 60mg once-daily dosing for the management of diabetic peripheral neuropathic pain, fibromyalgia, and chronic musculoskeletal pain due to chronic osteoarthritis pain and low back pain. Pain Practice 2013;13(3):239-52. [DOI: ] - PubMed
Sabourin 2013 {published data only}
    1. Sabourin G. Cymbalta. Also controls the pain of knee arthrosis. Perspective Infirmiere: Revue Officielle de l'Ordre des Infirmieres et Infirmiers du Quebec 2013;10(2):62. - PubMed
Sawynok 2003 {published data only}
    1. Sawynok J. Recent findings surrounding topical antidepressants as analgesics and review of existing and emerging topical analgesics. Advanced Studies in Medicine 2003;3(7A):S635-41.
Skljarevski 2009 {published data only}
    1. Skljarevski V, Chappell A, Desaiah D, Zhang S, Liu-Seifert H, Brown J, et al. Efficacy and safety of duloxetine in the treatment of pain associated with knee osteoarthritis. Journal of Pain 2009;1:S35. [DOI: ]
Skljarevski 2011 {published data only}
    1. Skljarevski V, Zhang S, Iyengar S, D'Souza D, Alaka K, Chappell A, et al. Efficacy of duloxetine in patients with chronic pain conditions. Current Drug Therapy 2011;6(4):296-303. [DOI: ] - PMC - PubMed
Sofat 2017 {published data only}
    1. Sofat N, Harrison A, Russel MD, Ayis S, Kiely PD, Baker EH, et al. The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis. Journal of Pain Research 2017;10:2437-49. - PMC - PubMed
Sullivan 2009a {published data only}
    1. Sullivan M, Bentley S, Fan MY, Gardner G. A single-blind placebo run-in study of venlafaxine XR for activity-limiting osteoarthritis pain. Pain Medicine 2009;10(5):806-12. [DOI: ] - PubMed
Sullivan 2009b {published data only}
    1. Sullivan MD, Bentley S, Fan MY, Gardner G. A single-blind, placebo run-in study of duloxetine for activity-limiting osteoarthritis pain. Journal of Pain 2009;10(2):208-13. [DOI: ] - PubMed
Talati 2010 {published data only}
    1. Talati D, Alaka K, Chappell A, D'Souza D, Iyengar S, Skljarevski V, et al. Efficacy of duloxetine in patients with chronic pain conditions. PM and R 2010;1:S30. - PMC - PubMed
Teran Estrada 2011 {published data only}
    1. Teran Estrada L, Carrillo Vazquez SM, Rizzoli A, Espinosa Cuervo G, Holguin Dorador GI, Perez Perez A, et al. Evidence-based recommendations on duloxetine treatment for the pain in knee and hip osteoarthritis: systematic review and expert consensus. Osteoarthritis and Cartilage 2011;19:S232.
Thorpe 1974 {published data only}
    1. Thorpe P, Marchant-Williams R. The role of an antidepressant, dibenzepin (Noveril), in the relief of pain in chronic arthritic states. Medical Journal of Australia 1974;1(8):264-6. - PubMed
Wang 2015 {published data only}
    1. Wang ZY, Shi SY, Li SJ, Chen F, Chen H, Lin HZ, et al. Efficacy and safety of duloxetine on osteoarthritis knee pain: a meta-analysis of randomized controlled trials. Pain Medicine (United States) 2015;16(7):1373-85. [DOI: ] - PubMed
Weng 2020 {published data only}
    1. Weng C, Xu J, Wang Q, Lu W, Liu Z. Efficacy and safety of duloxetine in osteoarthritis or chronic low back pain: a systematic review and meta-analysis. OARSI 2020;28(6):721-34. - PubMed
Williamson 2014 {published data only}
    1. Williamson OD, Schroer M, Ruff DD, Ahl J, Margherita A, Sagman D, et al. Onset of response with duloxetine treatment in patients with osteoarthritis knee pain and chronic low back pain: a post hoc analysis of placebo-controlled trials. Clinical Therapeutics 2014;36(4):544-51. [DOI: ] - PubMed
Wohlreich 2009 {published data only}
    1. Wohlreich MM, Sullivan MD, Mallinckrodt CH, Chappell AS, Oakes TM, Watkin JG, et al. Duloxetine for the treatment of recurrent major depressive disorder in elderly patients: treatment outcomes in patients with comorbid arthritis. Psychosomatics: Journal of Consultation and Liaison Psychiatry 2009;50(4):402-12. [DOI: ] - PubMed
Wohlreich 2013 {published data only}
    1. Wohlreich M, Frakes E, Risser RC, Ahl J. Duloxetine dose escalation in patients with osteoarthritis knee pain, who were taking optimized NSAIDs. Current Medical Research and Opinion 2013;29(8):879. [DOI: ] - PubMed

References to studies awaiting assessment

Abou‐Raya 2012 {published data only}
    1. Abou-Raya S, Abou-Raya A, Helmii M. Duloxetine for the management of pain in older adults with knee osteoarthritis: randomised placebo-controlled trial. Age and Aging 2012;41(5):646-52. - PubMed
Glick 1976 {published data only}
    1. Glick EN. A clinical trial of tofranil in osteo-arthritis. Journal of International Medical Research 1976;4(2 Suppl):20-2. - PubMed

References to ongoing studies

ACTRN12615000301561 {published data only}
    1. Does amitriptyline reduce pain in knee osteoarthritis?. Ongoing study. 7 July 2015. Contact author for more information.
ACTRN12619001082190 {published data only}
    1. Serotonin noradrenaline reuptake inhibitor (SNRI) medications for the treatment of osteoarthritis pain (STOP) trial. Ongoing study. 30 September 2019. Contact author for more information.
İlleez 2020 {unpublished data only}
    1. Comparison of the efficacy of duloxetine and pregabalin in patients with knee osteoarthritis with mix type pain. Ongoing study. October 2016. Contact author for more information.
IRCT20170716035126N2 {published data only}
    1. Evaluating the efficacy of duloxetine and gabapentin in pain reduction in patients with knee osteoarthritis. Ongoing study. March 2018. Contact author for more information.
ntr4798 {published data only}
    1. Duloxetine for chronic osteoarthritis pain; an important alternative?. Ongoing study. 1 April 2015. Contact author for more information.

Additional references

Allen 2009
    1. Allen KD, Coffman CJ, Golightly YM, Stechuchak KM, Keefe FJ. Daily pain variations among patients with hand, hip, and knee osteoarthritis. Osteoarthritis and Cartilage 2009;17(10):1275-82. [DOI: ] - PubMed
Altman 1986
    1. Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, et al. The American College of Rheumatology Criteria for the classification and reporting of osteoarthritis of the knee. Arthritis & Rheumatism 1986;29:1039-49. - PubMed
Altman 1991
    1. Altman R, Alarcón G, Appelrouth D, Bloch D, Borenstein D, Brandt K, et al. The American College of Rheumatology Criteria for the classification and reporting of osteoarthritis of the hip. Arthritis & Rheumatism 1991;34:505-14. - PubMed
Bair 2003
    1. Bair MJ, Robinson RL, Katon W, Kroenke K. Depression and pain comorbidity: a literature review. Archives of Internal Medicine 2003;163(20):2433-45. - PubMed
Bannuru 2019
    1. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zienstra SM, et al. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage 2019;27(11):1578-89. [DOI: 10.1016/j.joca.2019.06.011] - DOI - PubMed
Bartels 2007
    1. Bartels EM, Lund H, Hagen KB, Dagfinrud H, Christensen R, Danneskiold-Samsøe B. Aquatic exercise for the treatment of knee and hip osteoarthritis. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No: CD005523. [DOI: 10.1002/14651858.CD005523.pub2] - DOI - PubMed
Benyamin 2008
    1. Benyamin R, Trescot A, Datta S, Buenaventura R, Adlaka R, Sehgal N, et al. Opioid complications and side effects. Pain Physician 2008;11:S105-20. - PubMed
Black 2013
    1. Black C, Stokes L, Phillips C, Peloso PM, Mavros P, Everett SV, et al. A European assessment of the impact of inadequate pain relief on health-related quality of life in patients with knee osteoarthritis in the survey of real world therapies. Value in Health 2013;16(3):A228.
Cates 2008 [Computer program]
    1. Visual Rx. Dr Christopher Cates, Version 3. www.nntonline.net, 2008.
Cepeda 2006
    1. Cepeda MS, Camaro F, Zea C, Valencia L. Tramadol for osteoarthritis. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No: CD005522. [DOI: 10.1002/14651858.CD005522.pub2] - DOI - PubMed
Chappell 2009a
    1. Chappell AS, Ossanna MJ, Liu-Seifert H, Iyengar S, Skljarevski V, Li LC, et al. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13 week, randomised, placebo-controlled trial. Pain 2009;146(3):253-60. - PubMed
Chou 2017
    1. 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. Annals of Internal Medicine 2017;166(7):480-92. [DOI: 10.7326/M16-2458] - DOI - PubMed
Christensen 2007
    1. Christensen R, Bartels EM, Astrup A, Bliddal H. Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis. Annals of Rheumatic Diseases 2007;66:433-9. - PMC - PubMed
Citrome 2012
    1. Citrome L, Weiss-Citrome A. A systematic review of duloxetine for osteoarthritic pain: what is the number needed to treat, number needed to harm, and the likelihood to be helped or harmed? Postgraduate Medicine 2012;124(1):83-93. - PubMed
Cross 2014
    1. Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Annals of Rheumatic Diseases 2014;73:1323-30. - PubMed
Deeks 2021
    1. Deeks JJ, Higgins JP, Altman DG. Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Dharmshaktu 2012
    1. Dharmshaktu P, Tayal V, Kalra BS. Efficacy of antidepressants as analgesics: a review. Journal of Clinical Pharmacology 2012;52(1):6-17. - PubMed
Dworkin 2007
    1. Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence based recommendations. Pain 2007;132(3):237-51. - PubMed
Dworkin 2008
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. Journal of Pain 2008;9(2):105-21. - PubMed
eTG 2015
    1. Therapeutic Guidelines Limited. eTG Complete. www.tg.org.au (accessed prior to 4 September 2022).
Felson 2005
    1. Felson DT. The sources of pain in knee osteoarthritis. Current Opinion in Rheumatology 2005;17(5):624-8. - PubMed
Felson 2006
    1. Felson DT. Clinical practice. Osteoarthritis of the knee. New England Journal of Medicine 2006;354(8):841-8. - PubMed
Fransen 2014
    1. Fransen M, McConnell S, Hernandez-Molina G, Reichenbach S. Exercise for osteoarthritis of the hip. Cochrane Database of Systematic Reviews 2014, Issue 4. Art. No: CD007912. [DOI: 10.1002/14651858.CD007912.pub2] - DOI - PMC - PubMed
Fransen 2015
    1. Fransen M, McConnell S, Harmer AR, Esch M, Simic M, Bennell, KL. Exercise for osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No: CD004376. [DOI: 10.1002/14651858.CD004376.pub3] - DOI - PMC - PubMed
Ghogomu 2014
    1. Ghogomu EA, Maxwell LJ, Buchbinder R, Rader T, Pardo Pardo J, Johnston RV, et al, Editorial Board of the Cochrane Musculoskeletal Group. Updated method guidelines for Cochrane musculoskeletal group systematic reviews and metaanalyses. Journal of Rheumatology 2014;41(2):194-205. [DOI: 10.3899/jrheum.121306] - DOI - PubMed
GRADEpro GDT [Computer program]
    1. GRADEpro GDT. Version accessed 18 July 2018. Hamilton (ON): McMaster University (developed by Evidence Prime), 2015. Available at gradepro.org.
Häuser 2009
    1. Häuser W, Bernardy K, Üçeyler N, Sommer C. Treatment of fibromyalgia syndrome with antidepressants: a meta analysis. JAMA 2009;301(2):198-209. - PubMed
Hawker 2008
    1. Hawker GA, Stewart L, French MR, Cibere J, Jordan JM, March L, et al. Understanding the pain experience in hip and knee osteoarthritis – an OARSI/OMERACT initiative. Osteoarthritis and Cartilage 2008;16(4):415-22. [DOI: 10.1016/j.joca.2007.12.017] - DOI - PubMed
Heidari 2011
    1. Heidari B. Knee osteoarthritis prevalence, risk factors, pathogenesis and features: part I. Caspian Journal of Internal Medicine 2011;2(2):205-12. - PMC - PubMed
Higgins 2017
    1. Higgins JP, Altman DG, Sterne JA. Chapter 8: Assessing risk of bias in included studies. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0 (updated June 2017). The Cochrane Collaboration, 2017. Available from training.cochrane.org/handbook/archive/v5.2/.
Higgins 2021
    1. Higgins JP, Li T, Deeks JJ. Chapter 6: Choosing effect measures and computing estimates of effect. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Jüni 2015
    1. Jüni P, Hari R, Rutjes A, Fischer R, Silletta M, Reichenbach S, et al. Intra-articular corticosteroid for knee osteoarthritis. Cochrane Database of Systematic Reviews 2015, Issue 10. Art. No: CD005328. [DOI: 10.1002/14651858.CD005328.pub3] - DOI - PMC - PubMed
Linton 2011
    1. Linton SJ, Bergbom S. Understanding the link between depression and pain. Scandinavian Journal of Pain 2011;2(2):47-54. - PubMed
MIMS 2015
    1. MIMS Australia. MIMS Online. www.mimsonline.com.au (accessed prior to 4 September 2022).
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. Journal of Clinical Epidemiology 2009;62(10):1006-12. [DOI: ] - PubMed
Neogi 2013
    1. Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage 2013;21(9):1145-53. - PMC - PubMed
Nijs 2011
    1. Nijs J, Meeus M, Oosterwijck J, Roussel N, Kooning M, Ickmans K, et al. Treatment of central sensitisation in patients with 'unexplained' chronic pain: what options do we have? Expert Opinion on Pharmacotherapy 2011;12(7):1087-98. - PubMed
O'Leary 2018
    1. O'Leary H, Smart KM, Moloney NA, Blake C, Doody CM. Pain sensitization associated with nonresponse after physiotherapy in people with knee osteoarthritis. Pain 2018;159(9):1877-86. - PubMed
Page 2021
    1. Page MJ, Higgins JP, Sterne JA. Chapter 13: Assessing risk of bias due to missing results in a synthesis. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Pham 2004a
    1. Pham T, Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al. OMERACT-OARSI initiative: Osteoarthritis Research Society international set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis and Cartilage 2004;12(5):389-99. - PubMed
Pham 2004b
    1. Pham T, Heijde D, Altman RD. OMERACT-OARSI initiative: Osteoarthritis Research Society International set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthritis Cartilage 2004;12:389-99. [DOI: 10.1016/j.joca.2004.02.001] - DOI - PubMed
Review Manager 2014 [Computer program]
    1. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Richards 2011
    1. Richards BL, Whittle SL, Buchbinder R. Antidepressants for pain management in rheumatoid arthritis. Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No: CD008920. [DOI: 10.1002/14651858.CD008920.pub2] - DOI - PubMed
Rutjes 2009
    1. Rutjes AW, Nüesch E, Sterchi R, Kalichman L, Hendriks E, Osiri M, et al. Transcutaneous electrostimulation for osteoarthritis of the knee. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No: CD002823. [DOI: 10.1002/14651858.CD002823.pub2] - DOI - PMC - PubMed
Rutjes 2010
    1. Rutjes AW, Nüesch E, Sterchi R, Jüni P. Therapeutic ultrasound for osteoarthritis of the knee or hip. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No: CD003132. [DOI: 10.1002/14651858.CD003132.pub2] - DOI - PubMed
Saarto 2007
    1. Saarto T, Wiffen PJ. Antidepressants for neuropathic pain. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No: CD005454. [DOI: 10.1002/14651858.CD005454.pub2] - DOI - PMC - PubMed
Schünemann 2021a
    1. Schünemann HJ, Vist GE, Higgins JP, Santesso N, Deeks JJ, Glasziou P, et al. Chapter 15: Interpreting results and drawing conclusions. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Schünemann 2021b
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing 'Summary of findings' tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook/archive/v6.2.
Tallon 2000
    1. Tallon D, Chard J, Dieppe P. Exploring the priorities of patients with osteoarthritis of the knee. Arthritis Care and Research 2000;13:312-9. - PubMed
Thakur 2014
    1. Thakur M, Dickenson A, Baron R. Osteoarthritis pain: nociceptive or neuropathic? Nature Reviews. Rheumatism 2014;10(6):374-80. - PubMed
Towheed 2006
    1. Towheed T, Maxwell L, Judd M, Catton M, Hochberg MC, Wells GA. Acetaminophen for osteoarthritis. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No: CD004257. [DOI: 10.1002/14651858.CD004257.pub2] - DOI - PMC - PubMed
Urquhart 2010
    1. Urquhart DM, Hoving JL, Assendelft WJ, Roland M, Tulder MW. Antidepressants for non-specific low back pain. Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No: CD001703. [DOI: 10.1002/14651858.CD001703.pub3] - DOI - PMC - PubMed
Vos 2012
    1. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) 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. - PMC - PubMed
Wielage 2014
    1. Wielage RC, Patel AJ, Bansal M, Lee S, Klein RW, Happich M. Cost effectiveness of duloxetine for osteoarthritis: a Quebec societal perspective. Arthritis Care and Research 2014;66(5):702-8. - PubMed
Woolf 2011
    1. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain 2011;152(3 Suppl):S2-15. - PMC - PubMed
Zolio 2021
    1. Zolio L, LIm KY, McKenzie JE, Estee M, Hussain Sm, Cicuttini F, et al. Systematic review and meta-analysis of the prevalence of neuropathic-like pain and/or pain sensitization in people with knee and hip osteoarthritis. Osteoarthritis Cartilage 2021;21:S1063-4584. [DOI: 10.1016/j.joca.2021.03.021] [PMID: ] - DOI - PubMed

References to other published versions of this review

Lyttle 2016
    1. Lyttle JR, Urquhart DM, Cicuttini FM, Wluka AE. Antidepressants for osteoarthritis. Cochrane Database of Systematic Reviews. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No: CD012157. [DOI: 10.1002/14651858.CD012157] - DOI - PMC - PubMed

Publication types

Substances

Associated data

LinkOut - more resources