Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study

Wang, Guochun; Bi, Liqi; Li, X.; Li, Zhijun; Zhao, D.; Chen, Jinwei; He, D.; Wang, C.-N.; Dueñas, H.; Skljarevski, V.; Yue, Li

doi:10.1016/j.joca.2016.12.025

Cited by 45 publications

(19 citation statements)

References 22 publications

(19 reference statements)

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“…There were few differences in treatment regimen among the studies, with the duration ranging from 10 to 16 weeks. In one study, the participants had OA in either the knee or hip; however, for most patients (404/407, 99.3%), the affected joint was the knee . Besides the primary outcomes, which included chronic pain, joint stiffness, and physical function, reported in each study, five studies also reported TEAE, serious AE, and discontinuations.…”

Section: Resultsmentioning

confidence: 99%

“…With regard to randomisation and allocation concealment, one study 23 showed an unclear risk and the remaining five studies [20][21][22]24,25 all showed a low risk. Furthermore, all six studies appeared to be at low risk with regard to blindness, incomplete outcome data, and selective reporting, but they were unclear for other biases.…”

Section: Quality Assessmentmentioning

confidence: 99%

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Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta‐analysis of randomised controlled trials

et al. 2019

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Background Knee osteoarthritis (OA) is one of the most common joint diseases, and pharmacotherapy is necessary to control its symptoms. Aim To evaluate efficacy and tolerability of duloxetine in patients with knee OA. Methods PubMed, Web of Science, Embase, Cochrane Library and http://ClinicalTrials.gov were searched to identify randomised controlled trials comparing duloxetine with placebo for knee OA. Data including pain, stiffness, physical function, and adverse events were extracted for meta‐analysis. The protocol was prospectively registered in PROSPERO (CRD42018097110). Results Data from six randomised controlled trials including 2059 participants were pooled. Duloxetine achieved significant reductions in primary outcomes including Brief Pain Inventory 24‐h average pain score (weighted mean difference (WMD) = −0.74, 95% confidence interval (CI) = −0.92 to −0.57), weekly mean of the 24‐h average pain score (WMD = −0.76, 95% CI = −0.96 to −0.56), WOMAC stiffness score (WMD = −0.47, 95% CI = −0.60 to −0.34) and WOMAC physical function score (WMD = −4.44, 95% CI = −5.24 to −3.64). Furthermore, duloxetine demonstrated a higher number of treatment‐emergent adverse events (risk ratio (RR) = 1.31, 95% CI = 1.20–1.44) and discontinuations (RR = 2.26, 95% CI = 1.63–3.12); however, no difference in serious adverse events (RR = 0.92, 95% CI = 0.40–2.11) was observed. Conclusion Duloxetine is effective in the management of chronic pain and loss of physical function in knee OA with acceptable adverse events despite having no advantage in treating joint stiffness. Future trials should focus on determining the optimal treatment regimen.

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Section: Resultsmentioning

confidence: 99%

Section: Quality Assessmentmentioning

confidence: 99%

Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta‐analysis of randomised controlled trials

et al. 2019

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“…More recently, duloxetine-a centrally acting serotonin norepinephrine reuptake inhibitor-has been approved as an alternative means for treating OA pain. Multiple large multicenter RCTs in patients with knee OA, and meta-analysis of such studies, show that daily duloxetine (60/ 120 mg) in comparison to placebo results in a greater reduction in pain, improved function, and a patient-rated impression of improvement after 10-13 weeks of treatment (Chappell et al, 2009;Wang et al, 2015Wang et al, , 2016. Managing OA pain with centrally acting drugs is consistent with evidence demonstrating central abnormalities associated with OA (Baliki et al, 2008;Baliki, Schnitzer, Bauer, & Apkarian, 2011;Baliki, Mansour, Baria, & Apkarian, 2014;Gwilym, Filippini, Douaud, Carr, & Tracey, 2009;Hiramatsu et al, 2014;Parks et al, 2011).…”

Section: Dissemination Of Modern Pharmacotherapies Is Based On Clinicmentioning

confidence: 99%

Inferring distinct mechanisms in the absence of subjective differences: Placebo and centrally acting analgesic underlie unique brain adaptations

et al. 2018

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Development and maintenance of chronic pain is associated with structural and functional brain reorganization. However, few studies have explored the impact of drug treatments on such changes. The extent to which long-term analgesia is related to brain adaptations and its effects on the reversibility of brain reorganization remain unclear. In a randomized placebo-controlled clinical trial, we contrasted pain relief (3-month treatment period), and anatomical (gray matter density [GMD], assessed by voxel-based morphometry) and functional connectivity (resting state fMRI nodal degree count [DC]) adaptations, in 39 knee osteoarthritis (OA) patients (22 females), randomized to duloxetine (DLX, 60 mg once daily) or placebo. Pain relief was equivalent between treatment types. However, distinct circuitry (GMD and DC) could explain pain relief in each group: up to 85% of variance for placebo analgesia and 49% of variance for DLX analgesia. No behavioral measures (collected at entry into the study) could independently explain observed analgesia. Identified circuitry were outside of nociceptive circuitry and minimally overlapped with OA-abnormal or placebo response predictive brain regions. Mediation analysis revealed that changes in GMD and DC can influence each other across remote brain regions to explain observed analgesia. Therefore, we can conclude that distinct brain mechanisms underlie DLX and placebo analgesia in OA. The results demonstrate that even in the absence of differences in subjective pain relief, pharmacological treatments can be differentiated from placebo based on objective brain biomarkers. This is a crucial step to untangling mechanisms and advancing personalized therapy approaches for chronic pain.

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“…The Osteoarthritis Research Society International (OARSI) guidelines recommend duloxetine as treatment for multiple‐joint OA with or without comorbidities . Some RCTs and meta‐analyses revealed the efficacy and safety of duloxetine for OA pain . Moreover, the SNRIs, including duloxetine, are regarded as the first therapeutic agents for neuropathic pain .…”

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confidence: 99%

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

et al. 2019

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We investigated the efficacy of duloxetine on hyperalgesia, histopathological and radiographic findings, pain-related sensory innervation of dorsal-root ganglia (DRG), and spinal changes in a rat model of induced hip osteoarthritis (OA). The right hip joints of male Sprague-Dawley rats (n = 6 rats/group) in the Sham group were injected with 25 μl of sterile saline and 25 μl of sterile saline with 2 mg of monosodium iodoacetate (MIA) were injected to the MIA + Vehicle and MIA + Duloxetine groups. We injected duloxetine 20 mg/kg intraperitoneally in the MIA + Duloxetine group 28 days after injection, whereas rats in the MIA + Vehicle group were injected with 0.5 ml of 20% dimethyl sulfoxide. We assessed hyperalgesia, histopathological changes, immunoreactive (-ir) neurons for calcitonin generelated peptide and activating transcription factor 3 in DRG, and immunoreactive neurons for ionized-calcium-binding adaptor molecule 1 (Iba1) in the dorsal horn of the spinal cord. MIA administration into the hip joint let to mechanical hyperalgesia of the ipsilateral hind paw (p < 0.05). A single injection of duloxetine significantly attenuated it in induced hip OA (p < 0.05) and suppressed the number of Iba1-ir microglia of the ipsilateral dorsal horn (p < 0.05). These results suggest that a single injection of duloxetine suppressed mechanical hyperalgesia and may influence the expression of Iba1 in the microglia of the ipsilateral dorsal horn in the MIA-induced hip OA. This finding implies the inhibitory effects of duloxetine against neuropathic pain, which may lead to a change of microglial activities.

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Efficacy and safety of duloxetine in Chinese patients with chronic pain due to osteoarthritis: a randomized, double-blind, placebo-controlled study

Abstract: This study demonstrated the efficacy of duloxetine in Chinese patients with chronic pain due to OA. The safety profile of duloxetine observed in this study was consistent with that in previous duloxetine trials. This trial is registered with ClinicalTrials.gov (NCT01931475).

Cited by 45 publications

References 22 publications

Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta‐analysis of randomised controlled trials

Efficacy and tolerability of duloxetine in patients with knee osteoarthritis: a meta‐analysis of randomised controlled trials

Inferring distinct mechanisms in the absence of subjective differences: Placebo and centrally acting analgesic underlie unique brain adaptations

Analgesic Effect of Duloxetine on an Animal Model of Monosodium Iodoacetate‐Induced Hip Osteoarthritis

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