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Postgraduate Medicine Jan 2012To describe the efficacy, safety, and tolerability of duloxetine for the treatment of osteoarthritic pain. (Review)
Review
OBJECTIVE
To describe the efficacy, safety, and tolerability of duloxetine for the treatment of osteoarthritic pain.
DATA SOURCES
Systematic review of all published double-blind randomized controlled trials of duloxetine for osteoarthritic pain, supplemented by information in clinical trial registries, product labeling, and regulatory documents.
STUDY SELECTION
All available reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) for pain relief and other efficacy outcomes and number needed to harm (NNH) for relevant dichotomous adverse outcomes were extracted. Likelihood to be helped or harmed (LHH) was subsequently calculated.
DATA SYNTHESIS
US Food and Drug Administration approval for duloxetine for chronic pain associated with osteoarthritis (OA) was based on 2 randomized, double-blind, placebo-controlled clinical trials of 13 weeks' duration testing duloxetine 60 to 120 mg/d versus placebo. When study results were pooled, the proportion of patients experiencing clinically meaningful outcomes at study endpoint, such as a ≥ 30% or ≥ 50% reduction in pain scores, improvement in physical functioning, or subjective improvement, ranged from 42% to 67% for duloxetine, compared with 26% to 50% for placebo, depending on the specific measure; the NNT for these measures for duloxetine versus placebo was 7. The most commonly observed adverse reactions in duloxetine-treated patients were nausea (8.4% vs 2.0% for duloxetine and placebo, respectively), fatigue (6.7% vs 0.8%, respectively), and constipation (6.3% vs 0.8%, respectively), yielding NNH values of 16, 17, and 19, respectively. The LHH was consistently > 1.
CONCLUSIONS
Duloxetine appears efficacious and tolerable for the treatment of chronic pain associated with OA. The NNT and NNH can be used to quantify efficacy and tolerability outcomes and help place duloxetine into clinical perspective. Likelihood to be helped or harmed can illustrate to the clinician and patient the trade-offs between obtaining potential benefits versus harms. Head-to-head comparisons of duloxetine with other interventions for OA, as well as controlled trials of duloxetine in combination with other therapies, would be desirable.
Topics: Chronic Pain; Duloxetine Hydrochloride; Humans; Musculoskeletal Pain; Osteoarthritis; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Thiophenes
PubMed: 22314118
DOI: 10.3810/pgm.2012.01.2521 -
International Journal of Clinical... Feb 2024Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid consumption in patients after total hip or knee arthroplasty.
AIM
This systematic review and meta-analysis aimed to analyze pain control, opioid consumption, and associated adverse events of perioperative administration of duloxetine after total hip or knee arthroplasty.
METHOD
After being registered with PROSPERO (CRD42022323202), the databases of MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception until March 20, 2023, for randomized controlled trials (RCTs). Primary outcomes were the visual Analog Scale (VAS) pain scores at rest (rVAS) and upon ambulation (aVAS). Secondary outcomes were postoperative opioid consumption quantified as oral morphine milligram equivalents (MMEs) and adverse effects of duloxetine.
RESULTS
Nine RCTs with 806 cases were included. Duloxetine was associated with lower VAS scores at different times after surgery (24 h, two weeks, and ≥ 3 months). Compared to placebo, perioperative daily duloxetine use significantly reduced daily opioid MMEs at 24 h (standard mean deviation [SMD] -0.71, 95% confidence interval [95% CI] -1.19 to -0.24, P = 0.003), three days (SMD -1.10, 95% CI -1.70 to -0.50, P = 0.0003), and one week (SMD -1.18, 95% CI -1.99 to -0.38, P = 0.004) after surgery. The duloxetine group had a significantly lower rate of nausea (odds ratio 0.62, 95% CI [0.41 to 0.94], P = 0.02) and a higher rate of drowsiness and somnolence (odds ratio 1.87, 95% CI [1.13 to 3.07], P = 0.01) compared to the placebo group. No significant differences were observed in the rates of other adverse events.
CONCLUSION
Perioperative duloxetine significantly decreased postoperative pain and opioid consumption with good safety profiles. Further high quality designed and well-controlled randomized trials are warranted.
Topics: Humans; Analgesics, Opioid; Duloxetine Hydrochloride; Arthroplasty, Replacement, Hip; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37294475
DOI: 10.1007/s11096-023-01593-x -
Medicine Nov 2019Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term analgesic effect and safety of duloxetine in the treatment of OA.
METHODS
Electronic databases were searched in February 2019, including PUBMED, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science. All eligible studies should be randomized controlled trials (RCTs) comparing duloxetine treatment group to placebo about OA pain relief and safety outcomes.
RESULTS
Five RCTs with 2059 patients were involved in this systematic review and meta-analysis. Compared to placebo, duloxetine treatment showed significant better result, with higher reduction pain intensity (mean difference [MD] = -0.77, P < .00001), higher rates of both 30% and 50% reduction in pain severity (risk ratio [RR] = 1.42, P < .00001; RR = 1.62, P < .00001), lower mean Patient Global Improvement-Inventory (PGI-I) score (MD = -0.48, P < .00001). The results of the Western Ontario and McMaster Universities (WOMAC) score change from baseline to endpoint also favored duloxetine treatment group in all four categories, including total (MD = -5.43, P < .00001), pain (MD = -1.63, P = .001), physical function (MD = -4.22, P < .00001), and stiffness score (MD = -0.58, P < .00001). There were higher rates of treatment-emergent adverse events (TEAEs) (RR = 1.32, P < .00001) and discontinuation (RR = 1.88, P < .00001) in duloxetine group. However, there was no significant difference in the incidence of severe adverse events (SAEs) between these 2 groups (RR = 0.84, P = .68).
CONCLUSION
Duloxetine was an effective and safe choice to improve pain and functional outcome in OA patients. However, further studies are still needed to find out the optimal dosage for OA and examine its long-term efficacy and safety.
TRIAL REGISTRATION NUMBER
CRD42019128862.
Topics: Analgesics; Duloxetine Hydrochloride; Humans; Ontario; Osteoarthritis; Pain Measurement; Patient Acuity; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 31689755
DOI: 10.1097/MD.0000000000017541 -
Acta Psychiatrica Scandinavica Aug 2021Evidence of larger drug effects in highly standardized studies (efficacy) compared to clinical routine (effectiveness) is discussed as efficacy-effectiveness gap. This... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Evidence of larger drug effects in highly standardized studies (efficacy) compared to clinical routine (effectiveness) is discussed as efficacy-effectiveness gap. This study aimed to quantify effect size differences of RCTs and non-RCTs in the treatment of depression with venlafaxine and duloxetine and to identify effect modifying predictors.
METHODS
A comprehensive systematic review and meta-analysis was conducted, including all prospective trials, which evaluated the treatment effects of duloxetine or venlafaxine in patients with depression. The primary outcome was the pre-post effect size after acute therapy, which were compared between RCTs and non-RCTs. Moreover, an exploratory analysis of predictors in a mixed meta-regression model within an information-theoretic approach was performed.
RESULTS
171 RCTs and 74 non-RCTs were included. The pre-post effect size differed significantly between RCTs and non-RCTs (-3.04 vs. -2.62, Δ = 0.41, p = 0.012, high heterogeneity). Study characteristics were very similar between RCTs and non-RCTs. Most important variables to predict effect sizes were 'depression severity', 'dose' and 'number of participants'.
CONCLUSION
Despite differences in effect sizes between RCTs and non-RCTs, study design is not clearly an important predictor for the effect sizes. Our results question the common assumption that non-RCTs are generally better suited to describe a drug's effectiveness in clinical practice than RCTs. Future studies and their reporting should put more emphasis on the description of external validity, in order to allow better assessments of clinical relevance.
Topics: Antidepressive Agents; Depression; Duloxetine Hydrochloride; Humans; Prospective Studies; Venlafaxine Hydrochloride
PubMed: 33661520
DOI: 10.1111/acps.13293 -
BMC Neurology Nov 2010Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic... (Review)
Review
BACKGROUND
Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic pain causes psychological distress and impacts patient quality of life. Published literature for treatment in refractory patients is sparse and often published as conference abstracts only. The aim of this study was to identify published data for three pharmacological treatments: pregabalin, lidocaine plaster, and duloxetine, which are typically used at 2(nd) line or later in UK patients with neuropathic pain.
METHODS
A systematic review of the literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented with extensive conference and grey literature searching. Studies of any design (except single patient case studies) that enrolled adult patients with refractory NeP were included in the review and qualitatively assessed.
RESULTS
Seventeen studies were included in the review: nine of pregabalin, seven of the lidocaine plaster, and one of duloxetine. No head-to-head studies of these treatments were identified. Only six studies included treatments within UK licensed indications and dose ranges. Reported efficacy outcomes were not consistent between studies. Pain scores were most commonly assessed in studies including pregabalin; trials of pregabalin and the lidocaine plaster reported the proportion of responders. Significant improvements in the total, sensory and affective scores of the Short-form McGill Pain Questionnaire, and in function interference, sleep interference and pain associated distress, were associated with pregabalin treatment; limited or no quality of life data were available for the other two interventions. Limitations to the review are the small number of included studies, which are generally small, of poor quality and heterogeneous in patient population and study design.
CONCLUSIONS
Little evidence is available relevant to the treatment of refractory neuropathic pain despite the clinical need. There is a notable lack of high-quality comparative studies. It is evident that there is a need for future, high quality trials, particularly "gold-standard" RCTs in this refractory patient population.
Topics: Analgesics; Anesthetics, Local; Duloxetine Hydrochloride; Humans; Lidocaine; Neuralgia; Pregabalin; Thiophenes; Treatment Outcome; gamma-Aminobutyric Acid
PubMed: 21092100
DOI: 10.1186/1471-2377-10-116 -
Journal of Gynecology Obstetrics and... Mar 2022To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries.
METHODS
A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus from inception to September 2021. We selected randomized clinical trials (RCTs) that compared preoperative duloxetine (intervention group) versus placebo (control group) among women undergoing gynecologic laparoscopic surgeries. Our primary outcomes were pain scores evaluated by the Visual Analog Scale (VAS) at 2, 6, 12, and 24 h postoperatively. Our secondary outcomes were the time required for the first analgesic request in minutes, postoperative analgesic consumption in milligrams, length of hospital stay in days, and side effects.
RESULTS
Four RCTs with a total number of 244 patients were included in our systematic review and meta-analysis. We found duloxetine was linked to a significant reduction in VAS pain scores at different time intervals. The first analgesic request was significantly earlier in the placebo group than in the duloxetine group (p = 0.03). In addition, duloxetine significantly reduced the postoperative analgesic consumption compared to placebo (MD= -41.97, 95% CI [-53.23, -30.72], p<0.001). However, both groups did not differ in the length of hospital stay and side effects.
CONCLUSIONS
Duloxetine administration prior to gynecological laparoscopic surgeries is safe and effective in improving postoperative pain and analgesia.
Topics: Duloxetine Hydrochloride; Female; Gynecologic Surgical Procedures; Humans; Laparoscopy; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 34974147
DOI: 10.1016/j.jogoh.2021.102305 -
BMC Musculoskeletal Disorders Mar 2014This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis.
METHODS
A systematic literature review of English language articles was performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and opioids were included if treatment was ≥12 weeks and the Western Ontario and McMaster Universities Index (WOMAC) total score was available. Studies were assessed for quality using the assessment tool from the National Institute for Health and Clinical Excellence guidelines for single technology appraisal submissions.WOMAC baseline and change from baseline total scores were extracted and standardized. A frequentist meta-analysis, meta-regression, and indirect comparison were performed using the DerSimonian-Laird and Bucher methods. Bayesian analyses with and without adjustment for study-level covariates were performed using noninformative priors.
RESULTS
Thirty-two publications reported 34 trials (2 publications each reported 2 trials) that met inclusion criteria. The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo. Indirect comparisons to duloxetine found no significant differences for most of the compounds. Some analyses showed evidence of a difference with duloxetine for etoricoxib (better), tramadol and oxycodone (worse), but without consistent results between analyses. Forest plots revealed positive trends in overall efficacy improvement with baseline scores. Adjusting for baseline, the probability duloxetine is superior to other treatments ranges between 15% to 100%.Limitations of this study include the low number of studies included in the analyses, the inclusion of only English language publications, and possible ecological fallacy associated with patient level characteristics.
CONCLUSIONS
This analysis suggests no difference between duloxetine and other post-first line oral treatments for osteoarthritis (OA) in total WOMAC score after approximately 12 weeks of treatment. Significant results for 3 compounds (1 better and 2 worse) were not consistent across performed analyses.
Topics: Acetaminophen; Administration, Oral; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Drug Evaluation; Duloxetine Hydrochloride; Etoricoxib; Humans; Narcotics; Osteoarthritis; Pain Measurement; Pyridines; Sulfones; Thiophenes; Treatment Outcome
PubMed: 24618328
DOI: 10.1186/1471-2474-15-76 -
International Urology and Nephrology Jun 2013This systematic review determined whether the duloxetine can get more benefits versus placebo in managing women with stress urinary incontinence (SUI) all over the world. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
This systematic review determined whether the duloxetine can get more benefits versus placebo in managing women with stress urinary incontinence (SUI) all over the world.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing duloxetine with placebo in these patients. The eligible RCTs were identified from the following electronic databases: Cochrane CENTRAL, Medline and EMBASE. We treated the incontinence episode frequency (IEF) as the main outcome, and the secondary outcomes were cured, average voiding interval, incontinence quality of life (I-QOL), treatment-emergent adverse events (TEAEs) and discontinuation.
RESULTS
The review contained ten trials including 5,738 women who were randomized to take duloxetine or placebo. All arms in individual trials were comparable for various baseline characteristics. Individual studies showed a significantly greater decrease in IEF than placebo group. The total IEF responders (defined as a woman who had at least a 50 % decrease in IEF with treatment) within the duloxetine-treated women were more than the placebo-treated women (52.5 vs. 33.7 %; RR = 1.56; 95 %CI, 1.46-1.66; p < 0.00001). TEAEs were commonly experienced by both two groups (62.7 vs. 45.3 %) though they were not critical.
AUTHORS' CONCLUSIONS
Our meta-analysis showed that significant efficacy can be found in women treated with a certain dose of duloxetine. The adverse events like nausea, constipation, dry mouth, fatigue etc. are common.
Topics: Duloxetine Hydrochloride; Female; Humans; Quality of Life; Selective Serotonin Reuptake Inhibitors; Thiophenes; Treatment Outcome; Urinary Incontinence, Stress; Urination
PubMed: 23504618
DOI: 10.1007/s11255-013-0410-6 -
Rheumatology (Oxford, England) Mar 2011To evaluate and compare the efficacy and acceptability of the antidepressants amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) for FM syndrome (FMS). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate and compare the efficacy and acceptability of the antidepressants amitriptyline (AMT), duloxetine (DLX) and milnacipran (MLN) for FM syndrome (FMS).
METHODS
Cochrane Library, MEDLINE, SCOPUS, www.clinicalstudyresults.org and www.clinicalTrials.gov were searched for randomized pharmacological placebo-controlled trials until 30 May 2010. Outcomes of interest were symptom reduction [pain, fatigue, sleep disturbance and reduced health-related quality of life (HRQOL)] and acceptability (total drop-out rates). We performed a meta-analysis of each drug vs placebo using a random-effects model and adjusted indirect analyses of the three drugs. Methodological quality was assessed by the Cochrane risk of bias tool.
RESULTS
Ten AMT studies (612 patients), four DLX studies (1411 patients) and five MLN studies (4129 patients) met the inclusion criteria. The reported methodological quality of most AMT trials was poor, that of DLX and MLN were high. The three drugs were superior to placebo except DLX for fatigue, MLN for sleep disturbance and AMT for HRQOL. The significant effects of AMT and DLX were small and those of MLN not substantial. In adjusted indirect comparisons, AMT was superior to DLX and MLN in reduction of pain, sleep disturbances, fatigue and limitations of HRQOL. DLX was superior to MLN in reducing pain, sleep disturbances and limitations of HRQOL. MLN was superior to DLX in reducing fatigue. There were no significant differences in acceptability of the three drugs.
CONCLUSIONS
AMT cannot be regarded as the gold standard of FMS therapy with antidepressants because of the methodological limitations of its trials.
Topics: Amitriptyline; Antidepressive Agents; Cyclopropanes; Duloxetine Hydrochloride; Fibromyalgia; Humans; Milnacipran; Thiophenes; Treatment Outcome
PubMed: 21078630
DOI: 10.1093/rheumatology/keq354 -
European Urology Jan 2007Surgery and pelvic floor muscle training are established methods for treating stress urinary incontinence (SUI). A new serotonin and noradrenaline reuptake inhibitor,... (Review)
Review
OBJECTIVE
Surgery and pelvic floor muscle training are established methods for treating stress urinary incontinence (SUI). A new serotonin and noradrenaline reuptake inhibitor, duloxetine, has been studied in multiple phase 3 trials as a form of medical management of this condition. This systematic review determined the effectiveness and acceptability of duloxetine in managing SUI.
METHODS
We reviewed all randomised controlled trials comparing duloxetine with placebo or no treatment. The search included the Cochrane Incontinence Group specialised register, CENTRAL, MEDLINE, PREMEDLINE, dissertation abstracts, and the reference lists of relevant articles. The primary outcome was the number of participants whose symptoms were "cured" while on treatment. Secondary outcomes included subjective improvement, incontinent episodes, quality of life, adverse events, and discontinuation rates.
RESULTS
Nine trials were included, totalling 3063 women with predominantly SUI, all randomised to receive duloxetine or placebo. Treatment duration was 3-36 wk. Subjective cure favoured duloxetine (from three trials, 10.8% vs. 7.7%; RR=1.42; 95%CI, 1.02-1.98, p=0.04). The limited data available to assess objective cure rates were consistent with this. Individual studies showed a significant reduction in the Incontinence Episode Frequency (IEF) by approximately 50% during treatment. Duloxetine groups had significantly better quality-of-life scores (weighted mean difference for Incontinence Quality of Life Index for participants on 80 mg daily: 4.5; 95%CI, 2.83-6.18; p<0.00001) and rates of symptom improvement. Adverse effects were common (71% vs. 59%) but are reported as not serious and were equivalent to about one in eight participants reporting adverse effects (most commonly nausea) directly related to duloxetine treatment. About one in eight stopped treatment as a consequence of taking duloxetine (17% vs. 4%).
CONCLUSIONS
Duloxetine can significantly improve the quality of life of patients with SUI, but it is unclear whether or not benefits are sustainable. Side-effects such as nausea are common.
Topics: Adrenergic Uptake Inhibitors; Duloxetine Hydrochloride; Female; Humans; Quality of Life; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Thiophenes; Urinary Incontinence, Stress
PubMed: 17014950
DOI: 10.1016/j.eururo.2006.08.041