Comparative Efficacy and Safety of Six
Antidepressants and Anticonvulsants in Painful
Diabetic Neuropathy: A Network Meta-analysis

Background: Anticonvulsants and antidepressants are mostly used in management of painful diabetic neuropathy (PDN). However there are few direct comparisons between drugs of these classes, making evidence-based decision-making in the treatment of painful diabetic neuropathy difficult. Objectives: This study aimed to perform a network meta-analysis and benefit-risk analysis to evaluate the comparative efficacy and safety of these drugs in PDN treatment. Study Design: Comparative effectiveness study. Setting: Medical Education and Research facility in India. Methods: A comprehensive data search was done in PubMed, Cochrane, and Embase up to August 2012. We then systematically reviewed the studies which compared any of 6 drugs for the management of PDN: amitriptyline, duloxetine, gabapentin, pregabalin, valproate, and venlafaxine or any of their combinations. We performed a random-effects network meta-analysis to rank treatments in terms of efficacy and safety. We chose the number of patients experiencing ≥ 50% reduction in pain and number of patient withdrawals due to adverse events (AE) as primary outcomes for efficacy and safety, respectively. We also performed benefit-risk analysis, taking efficacy outcome as benefit and safety outcome as risk. Analysis was intention-to-treat. Results: We included 21 published trials in the analysis. Duloxetine, gabapentin, pregabalin, and venlafaxine were shown to be significantly efficacious compared to placebo with odds ratios (OR) of 2.12, 3.98, 2.78, and 4.43, respectively. Amitriptyline (OR: 7.03, 95% confidence interval [CI]: 1.87, 29.05) and duloxetine (OR: 3.26, 95% CI: 1.04, 9.97) caused more withdrawals than gabapentin. The ranking order of efficacy was gabapentin, venlafaxine, pregabalin, duloxetine/ gabapentin, duloxetine, amitriptyline, and placebo and the ranking order of safety was placebo, gabapentin, pregabalin, venlafaxine, duloxetine/gabapentin combination, duloxetine, and amitriptyline. Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin, duloxetine/gabapentin combination, duloxetine, placebo, and amitriptyline. Limitations: We could not include valproate in our analysis owing to the lack of studies reporting the dichotomous efficacy and safety outcomes. Conclusion: Gabapentin was found to be most efficacious and amitriptyline to be least safe among the treatments included in the study. Gabapentin showed most favorable balance between efficacy and safety. Key words: Amitriptyline, diabetic neuropathy, duloxetine, gabapentin, network meta-analysis, pain, pregabalin, valproate, valproic acid, venlafaxine

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Comparative efficacy and safety of intra-articular analgesics after knee arthroscopy: a Bayesian network meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2019-035346 ◽

2020 ◽

Vol 10 (9) ◽

pp. e035346

Author(s):

Yuchen He ◽

Hongyi He ◽

Dong-Xing Xie ◽

Xiaoxiao Li ◽

Yilun Wang

Keyword(s):

Single Dose ◽

Pain Relief ◽

Bayesian Network ◽

Knee Arthroscopy ◽

Meta Analysis ◽

Arthroscopic Surgery ◽

Cochrane Library ◽

Efficacy And Safety ◽

Comparative Efficacy ◽

Number Of Patients

IntroductionMost of the patients who received arthroscopic knee surgery will suffer moderate to severe pain, which can delay the rehabilitation process and increase the risk of postoperative complications. Therefore, seeking a safe and effective postoperative analgesia is necessary for promoting the application of arthroscopic surgery. This protocol aims to detail a planned systematic review and meta-analysis on the comparative efficacy and safety of single-dose intra-articular injection of analgesics for pain relief after knee arthroscopy.Method and analysisPubMed, Embase, Web of Science and Cochrane Library will be searched from inception to 1 June 2020 to retrieve randomised controlled trials (RCTs) that compared the commonly used single-dose intra-articular analgesics (ie, morphine; bupivacaine (including levobupivacaine); ropivacaine and magnesium alone or in combination) with placebo or between each other for postoperative pain relief among patients who had received knee arthroscopy. The primary outcome is pain intensity at 2-hour and 24-hour postoperatively; the secondary outcomes include side effects (eg, knee effusion, nausea, vomiting and flushing), the number of patients requiring supplementary analgesia and the time to first analgesic request. The methodological quality of the included RCTs will be assessed based on the Cochrane risk of bias table. The Bayesian network meta-analysis will be conducted using WinBUGS V.1.4.3.Ethics and disseminationSince no private or confidential patient data will be contained in the reporting, approval from an ethics committee is not required. Our study raises no ethical issue, and the results will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019130876.

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