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The International Journal of... Jan 2020The objective of this systematic review was to assess the analgesic efficacy of duloxetine (DLX) for fibromyalgia (FM) and find out which dosage between 60 mg/d DLX... (Meta-Analysis)
Meta-Analysis
The objective of this systematic review was to assess the analgesic efficacy of duloxetine (DLX) for fibromyalgia (FM) and find out which dosage between 60 mg/d DLX and 120 mg/d DLX was more suitable for clinical application. A systematic search through multiple databases (Cochrane Central Register of Controlled Trials (CENTRAL), ProQuest, PubMed) was conducted from 2000 until 7 March 2019. All steps were performed by two or more independent reviewers. The meta-analysis was performed to report the effects of DLX on pain reduction and its accompanied adverse events. This meta-analysis, including seven studies with 2642 FM patients, demonstrated that DLX could produce greater pain relief in FM than placebo (standardized mean difference (SMD) -0.26; 95% confidence interval (CI) -0.37 to -0.16). The risk ratio (RR) of at least 30% pain relief was 1.31 (95% CI 1.19 to 1.44); the RR of at least 50% pain relief was 1.46 (95% CI 1.28 to 1.67). However, the patients with DLX who suffered adverse events were more common than the ones with placebo (RR 1.17, 95% CI 1.12 to 1.23). The withdrawal effect included adverse event withdrawal and lack of efficacy withdrawal. The subgroup analyses of withdrawal effects demonstrated that 120 mg/d DLX had a higher incidence (RR 0.96, 95% CI 0.80 to 1.15) than 60 mg/d DLX (RR 0.77, 95% CI 0.63 to 0.93). In general, DLX was a great choice for pain relief in FM. Moreover, 60 mg/d DLX produced less withdrawal effects than 120 mg/d DLX. HighlightsFibromyalgia (FM) is a chronic condition of unknown aetiology, characterized by widespread pain and often associated with other symptoms.Duloxetine (DLX), a serotonin norepinephrine (noradrenaline) reuptake inhibitor (SNRI), is used to treat FM in many countries.DLX can produce greater pain relief in FM than placebo.DLX can bring about more adverse events than placebo.60 mg/d DLX produces less withdrawal than 120 mg/d DLX for FM patients.
Topics: Analgesics; Duloxetine Hydrochloride; Fibromyalgia; Humans; Pain
PubMed: 31487217
DOI: 10.1080/00207454.2019.1664510 -
Acta Psychiatrica Scandinavica Apr 2011To determine the short-term antidepressant efficacy and tolerability of duloxetine and venlafaxine vs. each other, placebo, selective serotonin reuptake inhibitors... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the short-term antidepressant efficacy and tolerability of duloxetine and venlafaxine vs. each other, placebo, selective serotonin reuptake inhibitors (SSRIs), and tri- and tetracyclic antidepressants (TCAs) in adults with major depression.
METHOD
Meta-analysis of randomised controlled trials identified through bibliographical databases and other sources, including unpublished manufacturer reports.
RESULTS
Fifty-four studies including venlafaxine arms (n = 12,816), 14 including duloxetine arms (n = 4,528), and two direct comparisons (n = 836) were analysed. Twenty-three studies were previously unpublished. In the meta-analysis, both duloxetine and venlafaxine showed superior efficacy (higher remission and response rates) and inferior tolerability (higher discontinuation rates due to adverse events) to placebo. Venlafaxine had superior efficacy in response rates but inferior tolerability to SSRIs (OR = 1.20, 95% CI 1.07-1.35 and 1.38, 95% CI 1.15-1.66, respectively), and no differences in efficacy and tolerability to TCAs. Duloxetine did not show any advantages over other antidepressants and was less well tolerated than SSRIs and venlafaxine (OR = 1.53, 95% CI 1.10-2.13 and OR 1.79, 95% CI 1.16-2.78, respectively).
CONCLUSION
Rather than being a first-line option, venlafaxine appears to be a valid alternative in patients who do not tolerate or respond to SSRIs or TCAs. Duloxetine does not seem to be indicated as a first-line treatment.
Topics: Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Cyclohexanols; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Resistance; Duloxetine Hydrochloride; Humans; Pharmacological Phenomena; Randomized Controlled Trials as Topic; Remission Induction; Therapeutic Equivalency; Thiophenes; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 20831742
DOI: 10.1111/j.1600-0447.2010.01599.x -
The Clinical Journal of Pain Nov 2016To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN). (Review)
Review
OBJECTIVE
To systematically review the evidence for duloxetine in the management of painful diabetic neuropathy (PDN).
METHODS
Electronic searches of Medline and PubMed were performed from 2005 till October 2015 using medical subject headings and free-text words. Two independent reviewers extracted the data and assessed the methodological quality of the selected studies.
RESULTS
Twenty-three studies met our inclusion criteria and 8 were considered of high quality and were included to this review. Because of heterogeneity of the studies included in this review, statistical pooling of the data was not possible. We found good evidence for use of duloxetine in PDN over placebo and pregabalin but there was no benefit of duloxetine over amitriptyline.
CONCLUSIONS
Duloxetine has a beneficial effect over placebo. Nevertheless, the evidence of superiority of duloxetine over pregabalin and amitriptyline should be explored further as there was only 1 trial for each category. Provided majority of the PDN patients share cardiovascular complications, use of duloxetine will be a good option for treating pain associated with PDN over amitriptyline. Future randomized controlled trials should be designed keeping this in mind.
Topics: Analgesics; Diabetic Neuropathies; Duloxetine Hydrochloride; Humans; Neuralgia; Randomized Controlled Trials as Topic
PubMed: 26710221
DOI: 10.1097/AJP.0000000000000343 -
Drug Safety 2009Second-generation antidepressants dominate the management of patients with major depressive disorder (MDD). Evidence on the general and comparative benefits and harms is... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Second-generation antidepressants dominate the management of patients with major depressive disorder (MDD). Evidence on the general and comparative benefits and harms is still accruing.
OBJECTIVE
To systematically review the general and comparative efficacy and safety of duloxetine for the treatment of acute-phase MDD in adults.
DATA SOURCES
We conducted a search of MEDLINE, Embase, PsychLit, The Cochrane Library, and the International Pharmaceutical Abstracts from 1980 to July 2009, as well as manually searching reference lists of pertinent review articles and exploring the Center for Drug Evaluation and Research database to identify unpublished research.
STUDY SELECTION
For efficacy, randomized controlled trials (RCTs) comparing duloxetine with placebo or second-generation antidepressants were included. For safety, both experimental and observational studies were eligible.
DATA EXTRACTION
Abstracts and full-text articles were independently reviewed by two people, one investigator extracted relevant data, and a senior reviewer checked data for completeness and accuracy.
RESULTS
We included 36 experimental and observational studies and, where sufficient data were available, meta-analyses of RCTs were conducted. Findings indicated that duloxetine is an effective treatment option for acute-phase MDD, with a tolerability profile similar to other second-generation antidepressants. No substantial differences in efficacy and safety appear to exist when duloxetine is compared with other second-generation antidepressants. Overall, about 40% of patients treated with duloxetine achieved remission. Compared with other treatments, duloxetine had frequently higher rates of nausea, vomiting and dry mouth; however, these differences did not lead to higher discontinuation rates compared with selective serotonin reuptake inhibitors as a class. There is insufficient evidence to draw conclusions about rare but severe adverse events.
CONCLUSIONS
Current evidence does not warrant the choice of duloxetine over other second-generation antidepressants based on greater efficacy or safety for patients with acute-phase MDD with or without accompanying symptoms such as pain.
Topics: Antidepressive Agents; Body Weight; Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Nausea; Randomized Controlled Trials as Topic; Serotonin Syndrome; Thiophenes
PubMed: 19916583
DOI: 10.2165/11318930-000000000-00000 -
Frontiers in Pharmacology 2022Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial....
Treatment of chemotherapy-induced peripheral neuropathy (CIPN) is challenging for clinicians, and many clinical trials and meta-analyses on CIPN are controversial. There are also few comparisons of the efficacy among drugs used to treat CIPN. Therefore, this systematic review aimed to study the efficacy of drugs in treating CIPN using existing randomized controlled trials. Electronic databases were searched for randomized controlled trials (RCTs) involving any pharmaceutical intervention and/or combination therapy of treating CIPN. Seventeen RCTs investigating 16 drug categories, duloxetine, pregabalin, crocin, tetrodotoxin, venlafaxine, monosialotetrahexosyl ganglioside (GM1), lamotrigine, KA (ketamine and amitriptyline) cream, nortriptyline, amitriptyline, topical (bitter apple) oil, BAK (baclofen, amitriptyline hydrochloride, and ketamine) pluronic lecithin organogel, gabapentin, and acetyl l-carnitine (ALC), in the treatment of CIPN were retrieved. Many of the included RCTs consisted of small sample sizes and short follow-up periods. It was difficult to quantify due to the highly variable nature of outcome indicators. Duloxetine, venlafaxine, pregabalin, crocin, tetrodotoxin, and monosialotetrahexosyl ganglioside exhibited some beneficial effects in treating CIPN. Duloxetine, GM1, and crocin showed moderate benefits based on the evidence review, while lamotrigine, KA cream, nortriptyline, amitriptyline, and topical (bitter apple) oil were not beneficial. Further studies were necessary to confirm the efficacy of gabapentin in the treatment of CIPN because of the controversy of efficacy of gabapentin. Furthermore, BAK topicalcompound analgesic gel only had a tendency to improve the CIPN symptoms, but the difference was not statistically significant. ALC might result in worsening CIPN. Most studies were not of good quality because of small sample sizes. Therefore, standardized randomized controlled trials with large samples were needed to critically assess the effectiveness of these drugs in treating CIPN in the future.
PubMed: 36618919
DOI: 10.3389/fphar.2022.1080888 -
Osteoarthritis and Cartilage Jun 2020To evaluate the efficacy and safety of duloxetine in the treatment of patients with osteoarthritis (OA) or chronic low back pain (CLBP). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of duloxetine in the treatment of patients with osteoarthritis (OA) or chronic low back pain (CLBP).
METHODS
Relevant randomized controlled trials (RCTs) were searched in PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Included RCTs compared the efficacy and safety of duloxetine vs placebo in the treatment of OA or CLBP. Weighted mean difference (WMD) were calculated for continuous outcomes while risk ratio (RR) were calculated for dichotomous outcomes.
RESULTS
Nine RCTs were included in our meta-analysis. Duloxetine had significant improvement over placebo in Brief Pain Inventory 24-h average pain [WMD: -0.67; 95% confidence interval (CI):-0.80, -0.53], weekly mean of the 24-h average pain (WMD: -0.65; 95% CI: -0.79, -0.52), Patient's Global Impression of Improvement (WMD: -0.41; 95% CI: -0.49, -0.32), Clinical Global Impression of Severity (WMD: -0.32; 95% CI: -0.38, -0.25), European Quality of Life Questionnaire-5 Dimension (WMD: 0.04; 95% CI: 0.02, 0.07). In addition, duloxetine is associated with more treatment-emergent adverse events (TEAEs) (RR: 1.25; 95% CI: 1.17, 1.33) and discontinuations for adverse events (AEs) (RR: 2.31; 95% CI: 1.81, 2.94). However, there was no statistically significant difference in serious AEs between duloxetine and placebo.
CONCLUSION
Duloxetine had modest to moderate effects on pain relief, function improvement, mood regulation and improvement in quality of life with mild AEs in the treatment of OA or CLBP. Future RCTs should focus on comparing duloxetine with other oral drugs and assessing the long-term safety of duloxetine.
Topics: Analgesics; Chronic Pain; Duloxetine Hydrochloride; Humans; Low Back Pain; Osteoarthritis; Treatment Outcome
PubMed: 32169731
DOI: 10.1016/j.joca.2020.03.001 -
Pain Medicine (Malden, Mass.) Sep 2023The purpose of this study was to investigate the analgesic effects of duloxetine, specifically on postoperative pain, opioid consumption, and related side effects... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The purpose of this study was to investigate the analgesic effects of duloxetine, specifically on postoperative pain, opioid consumption, and related side effects following total hip or knee arthroplasty.
METHODS
In this systematic review and meta-analysis, Medline, Cochrane, EMBASE, Scopus, and Web of Science were searched until November 2022 for studies which compared duloxetine with placebo when added to routine pain management protocols. Individual study risk of bias assessment was conducted based on Cochrane risk of bias tool 2. Random effect model meta-analysis was done on mean differences, to evaluate the outcomes.
RESULTS
Nine randomized clinical trials (RCT) were included in the final analysis, totaling 806 patients. Duloxetine reduced opioid consumption (oral morphine milligram equivalents) on postoperative days (POD) 2 (mean difference (MD): -14.35, P = .02), POD 3 (MD: -13.6, P < .001), POD 7 (MD: -7.81, P < .001), and POD 14 (MD: -12.72, P < .001). Duloxetine decreased pain with activity on POD 1, 3, 7, 14, 90 (All P < .05), and pain at rest on POD 2, 3, 7, 14, and 90 (all P < .05). There was no significant difference in the prevalence of the side effects, except for increased risk of somnolence/drowsiness (risk ratio: 1.87, P = .007).
CONCLUSION
Current evidence shows low to moderate opioid sparing effects of perioperative duloxetine and a statistically but not clinically significant reduction in pain scores. Patients treated with duloxetine had an increased risk for somnolence and drowsiness.
Topics: Humans; Analgesics, Opioid; Duloxetine Hydrochloride; Arthroplasty, Replacement, Hip; Sleepiness; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37027215
DOI: 10.1093/pm/pnad045 -
The Cochrane Database of Systematic... Oct 2022Although pain is common in osteoarthritis, most people fail to achieve adequate analgesia. Increasing acknowledgement of the contribution of pain sensitisation has... (Review)
Review
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.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Duloxetine Hydrochloride; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 36269595
DOI: 10.1002/14651858.CD012157.pub2 -
The Aging Male : the Official Journal... Dec 2022Postprostatectomy urinary incontinence (PPUI) is a serious complication despite surgical advances. Treatment options for PPUI include conservative care like Pelvic floor... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Postprostatectomy urinary incontinence (PPUI) is a serious complication despite surgical advances. Treatment options for PPUI include conservative care like Pelvic floor muscle exercise (PFME), which is a physiotherapy performed by the patients themselves; Pelvic floor muscle therapy (PFMT), a physiotherapy performed under the guidance of a therapist, and duloxetine treatment; and surgical interventions. In this study, network meta-analysis (NMA) was performed for direct comparison of these treatment options.
MATERIALS AND METHODS
The NMA pooled the odds ratios and 95% credible intervals using the number of patients achieving urinary continence and the total number of patients in an intention-to-treat population. The treatments were ranked based on the surface under the cumulative ranking curve (SUCRA) probabilities and the rankograms.
RESULTS
The pooled overall ORs of patients achieving urinary continence compared with no treatment was 1.73 (95% CrI: 0.657, 4.71) in PFME, 2.62 (95% CrI: 0.553, 13.5) in PFME plus Duloxetine, and 4.05 (95% CrI: 1.70, 10.2) in PFMT. The SUCRA values of ranking probabilities for each treatment showed high rates of continence in the order of PFMT, PFME plus Duloxetine, and PFME.
CONCLUSION
The results suggest that patients with PPUI should undergo PFMT and consider duloxetine as an additional treatment option.
Topics: Duloxetine Hydrochloride; Exercise Therapy; Female; Humans; Male; Network Meta-Analysis; Pelvic Floor; Treatment Outcome; Urinary Incontinence
PubMed: 35535703
DOI: 10.1080/13685538.2022.2069238 -
Journal of Child and Adolescent... Jun 2023Childhood mental illness is an ongoing public health crisis which is accompanied by an increase in antidepressant (i.e., serotonin reuptake inhibitors and... (Review)
Review
Childhood mental illness is an ongoing public health crisis which is accompanied by an increase in antidepressant (i.e., serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) use in children. Recent evidence highlighting the cultural differences in the utilization, efficacy, and tolerability of antidepressants in children underscores the need for diverse samples in studies examining antidepressant use. Furthermore, the American Psychological Association in recent years has emphasized the importance of including participants from diverse backgrounds in research studies, including investigations of medication efficacy. The present study, therefore, examined the demographic composition of samples used and reported in antidepressant efficacy and tolerability studies with children and adolescents experiencing anxiety and/or depression in the last decade. A systematic literature review utilizing two databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In line with the extant literature, antidepressants were operationalized as , , , , and Out of the 11 articles included in this review, 71% reported having a primarily adolescent sample (i.e., over 50% of the sample was 12 years or older). In addition, studies omitted any transgender, genderqueer, or gender-nonconforming demographics, and one study omitted all racial demographic information. While 64% of studies only partially reported racial demographic information, 36% of studies omitted ethnicity demographics altogether. The present study addresses a gap in the literature by supporting a lack of diversity in studies examining antidepressant use in children and adolescents. Furthermore, it underscores the importance of future studies using a more diverse and representative sample. Limitations of the present study included limited generalizability and the lack of independent and blind reviewer process. Possible explanations for the lack of inclusion and suggestions on how to address these disparities are discussed.
Topics: Child; Adolescent; Humans; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Fluoxetine; Sertraline; Duloxetine Hydrochloride
PubMed: 37253162
DOI: 10.1089/cap.2022.0090