Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis

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Abstract

About 21% of adults with osteoarthritis (OA) are diagnosed with concomitant depression in addition to chronic pain. Duloxetine, an anti-depressant medication, has been recently approved for managing Knee OA. We performed a systematic review to ascertain the efficacy and safety of duloxetine for OA. We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to December 2018. Randomized clinical trials (RCTs) assessing the efficacy and/or safety of duloxetine versus placebo in OA patients were included. Data extraction and quality assessment were undertaken by two independent reviewers. Seven RCTs (n = 2,102 participants) met our inclusion criteria, and five RCTs (n = 1,713) were eligible for meta-analysis. The results of our analyses indicate that duloxetine has statistically significant, moderate benefits on pain, function, and quality of life in knee OA patients for up to 13 weeks. Reported incidences of gastrointestinal adverse events were three to four times higher in participants who received duloxetine versus placebo. Duloxetine may be an effective treatment option for individuals with knee OA, but use of the drug is associated with a significantly higher risk of adverse events. Patient preferences and clinicians’ judgment must be considered before the initiation of duloxetine.

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Sensitization in patients with painful knee osteoarthritis.

Lars Arendt-Nielsen, Hongling Nie, Mogens B Laursen … (2010)

Pain is the dominant symptom in osteoarthritis (OA) and sensitization may contribute to the pain severity. This study investigated the role of sensitization in patients with painful knee OA by measuring (1) pressure pain thresholds (PPTs); (2) spreading sensitization; (3) temporal summation to repeated pressure pain stimulation; (4) pain responses after intramuscular hypertonic saline; and (5) pressure pain modulation by heterotopic descending noxious inhibitory control (DNIC). Forty-eight patients with different degrees of knee OA and twenty-four age- and sex-matched control subjects participated. The patients were separated into strong/severe (VAS>or=6) and mild/moderate pain (VAS<6) groups. PPTs were measured from the peripatellar region, tibialis anterior (TA) and extensor carpi radialis longus muscles before, during and after DNIC. Temporal summation to pressure was measured at the most painful site in the peripatellar region and over TA. Patients with severely painful OA pain have significantly lower PPT than controls. For all locations (knee, leg, and arm) significantly negative correlations between VAS and PPT were found (more pain, more sensitization). OA patients showed a significant facilitation of temporal summation from both the knee and TA and had significantly less DNIC as compared with controls. No correlations were found between standard radiological findings and clinical/experimental pain parameters. However, patients with lesions in the lateral tibiofemoral knee compartment had higher pain ratings compared with those with intercondylar and medial lesions. This study highlights the importance of central sensitization as an important manifestation in knee OA.

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Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage

Carlos Sostres, Carla Gargallo, Angel Lanas (2013)

NSAIDs are among the most commonly used drugs worldwide and their beneficial therapeutic properties are thoroughly accepted. However, they are also associated with gastrointestinal (GI) adverse events. NSAIDs can damage the whole GI tract including a wide spectrum of lesions. About 1 to 2% of NSAID users experienced a serious GI complication during treatment. The relative risk of upper GI complications among NSAID users depends on the presence of different risk factors, including older age (>65 years), history of complicated peptic ulcer, and concomitant aspirin or anticoagulant use, in addition to the type and dose of NSAID. Some authors recently reported a decreasing trend in hospitalizations due to upper GI complications and a significant increase in those from the lower GI tract, causing the rates of these two types of GI complications to converge. NSAID-induced enteropathy has gained much attention in the last few years and an increasing number of reports have been published on this issue. Current evidence suggests that NSAIDs increase the risk of lower GI bleeding and perforation to a similar extent as that seen in the upper GI tract. Selective cyclooxygenase-2 inhibitors have the same beneficial effects as nonselective NSAIDs but with less GI toxicity in the upper GI tract and probably in the lower GI tract. Overall, mortality due to these complications has also decreased, but the in-hospital case fatality for upper and lower GI complication events has remained constant despite the new therapeutic and prevention strategies.

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Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial.

Amy Chappell, Smriti Iyengar, H Seifert … (2009)

Pain is a common cause of disability in osteoarthritis. Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), has demonstrated analgesic effects in diabetic peripheral neuropathy and fibromyalgia. Considering its central mechanism of action, duloxetine may be effective in other pain states with evidence of central sensitization. Herein, we report the results of a 13-week, randomized, double-blind, placebo-controlled trial of duloxetine (60-120 mg/day) versus placebo in the treatment of knee pain in 231 patients meeting clinical and radiographic criteria for osteoarthritis of the knee. Duloxetine was superior to placebo on the primary efficacy measure (weekly mean 24-h pain scores) beginning at Week 1 and continuing through the treatment period (P < or = .05). There was also a significant improvement in the WOMAC physical functioning subscale and several other secondary outcomes. Adverse-event rates did not differ significantly between treatment groups (49.5% for duloxetine 60-120 mg/day, and 40.8% for placebo).

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Author and article information

Journal

Journal ID (nlm-ta): Korean J Intern Med

Journal ID (iso-abbrev): Korean J. Intern. Med

Journal ID (publisher-id): KJIM

Title: The Korean Journal of Internal Medicine

Publisher: The Korean Association of Internal Medicine

ISSN (Print): 1226-3303

ISSN (Electronic): 2005-6648

Publication date (Print): September 2019

Publication date (Electronic): 15 March 2019

Volume: 34

Issue: 5

Pages: 966-973

Affiliations

Center for Treatment Comparison and Integrative Analysis (CTCIA), Division of Rheumatology, Tufts Medical Center, Boston, MA, USA

Author notes

Correspondence to Raveendhara R. Bannuru, M.D. Center for Treatment Comparison and Integrative Analysis (CTCIA), Division of Rheumatology, Tufts Medical Center, Box 406, 800 Washington St, Boston, MA 02111, USA Tel: +1-617-636-8284 Fax: +1-617-636-1542 E-mail: rbannuru@ 123456tuftsmedicalcenter.org

Article

Publisher ID: kjim-2018-460

DOI: 10.3904/kjim.2018.460

PMC ID: 6718752

PubMed ID: 30871298

SO-VID: 9f1c4ed1-827b-4f81-a6fe-cdf8d48097c6

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 21 December 2018

Date accepted : 07 January 2019

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Efficacy and safety of duloxetine in osteoarthritis: a systematic review and meta-analysis

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Most cited references 25

Sensitization in patients with painful knee osteoarthritis.

Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage

Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: a 13-week, randomized, placebo-controlled trial.

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