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Journal of Orthopaedic Surgery and... Mar 2024There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we... (Meta-Analysis)
Meta-Analysis
PURPOSE
There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA.
METHODS
As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions.
RESULTS
Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = - 0.50, 95% confidence intervals [CI]: -0.70 to - 0.31, P < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P = 0.02, I = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P = 0.02, I = 0%).
CONCLUSION
Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA.
Topics: Humans; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Duloxetine Hydrochloride; Pain, Postoperative; Randomized Controlled Trials as Topic; Analgesics
PubMed: 38481321
DOI: 10.1186/s13018-024-04648-5 -
Systematic Reviews Apr 2022Duloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use compared to non-elderly is not clearly...
Tolerability of duloxetine in elderly and in non-elderly adults: a protocol of a systematic review and individual participant data meta-analysis of randomized placebo-controlled trials.
BACKGROUND
Duloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use compared to non-elderly is not clearly assessed. This protocol outlines a systematic review and individual participant data meta-analysis comparing the tolerability of duloxetine between elderly and non-elderly.
METHODS
Searches will be conducted in PubMed, ClinicalTrials.gov , Clinicaltrialsregister.eu, data sharing platforms, FDA drug approval packages, European public assessment reports and withdrawn applications from the EMA website. The review will be performed on studies available in electronic databases from their date of inception to the 31 March 2022. Only randomized controlled clinical trials, comparing duloxetine to placebo, will be included in this meta-analysis. The studies will be selected if they comprise both elderly and non-elderly adults, in conditions of use of duloxetine approved by the European Medical Agency (EMA) and the Food and Drug Administration (FDA). The primary outcome will be the rate ratio of serious adverse events under duloxetine compared to placebo, between participants at least 65 years old and non-elderly. Second, the number of any adverse events, clinical efficacy and quality of life will be compared between elderly and non-elderly under both interventions. The quality of evidence in the tolerability of duloxetine will be assessed using the GRADE system. A one or two-stage individual participant data random effect meta-analysis will be conducted depending on the availability of the data.
DISCUSSION
This meta-analysis will investigate the tolerability safety of duloxetine in the elderly population across all conditions approved by European and American regulatory authorities. The results from this meta-analysis are intended to help prescribers to provide better care for the elderly population.
SYSTEMATIC REVIEW REGISTRATION
The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42019130488 ).
Topics: Adult; Aged; Antidepressive Agents; Duloxetine Hydrochloride; Humans; Meta-Analysis as Topic; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Treatment Outcome
PubMed: 35428340
DOI: 10.1186/s13643-022-01945-0 -
Revista Da Associacao Medica Brasileira... Jun 2021Stress-type and urgency-type urinary incontinence are seen together in mixed-type urinary incontinence. Treatment is usually chosen according to the predominant type of...
OBJECTIVE
Stress-type and urgency-type urinary incontinence are seen together in mixed-type urinary incontinence. Treatment is usually chosen according to the predominant type of incontinence. The aim of this study is to evaluate the effect of mirabegron and duloxetine combination in the treatment of mixed-type urinary incontinence.
METHODS
The data of 88 mixed-type urinary incontinence patients who applied to the urology outpatient clinic between January 2018 and December 2019 were retrospectively analyzed. We applied mirabegron and duloxetine treatment to the patients. The International Consultation of Incontinence Questionnaire-Short Form, Overactive bladder symptom score questionnaire and daily pad count were statistically evaluated before and after the treatment.
RESULTS
Statistically significant improvements were observed using the questionnaire forms and decreased daily pad usage after the eight-week treatment (p<0.001). Based on the clinical global effect scale, 62.50% of patients had a partial or complete response to treatment and also the use of daily pads were decreased from 3.7-0.89 on an average.
CONCLUSION
Combination use of mirabegron and duloxetine in the treatment of mixed-type urinary incontinence improved symptom scores and decreased pad usage.
Topics: Acetanilides; Double-Blind Method; Duloxetine Hydrochloride; Humans; Retrospective Studies; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence
PubMed: 34550261
DOI: 10.1590/1806-9282.20201166 -
PLoS Medicine Nov 2021The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective...
BACKGROUND
The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths.
METHODS AND FINDINGS
A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates.
CONCLUSIONS
Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Cohort Studies; Congenital Abnormalities; Denmark; Duloxetine Hydrochloride; Female; Humans; Maternal Exposure; Middle Aged; Pregnancy; Risk Factors; Stillbirth; Sweden; Young Adult
PubMed: 34807906
DOI: 10.1371/journal.pmed.1003851 -
F1000Research 2023Treatment of neuropathic pain is challenging. Pregabalin and duloxetine are used as first-line therapy. Various international guidelines recommend a combination of... (Randomized Controlled Trial)
Randomized Controlled Trial
Treatment of neuropathic pain is challenging. Pregabalin and duloxetine are used as first-line therapy. Various international guidelines recommend a combination of first-line agents for the management of neuropathic pain. The objective of this study was to evaluate the efficacy and safety of a fixed-dose combination (FDC) of low-dose pregabalin and duloxetine compared to pregabalin monotherapy at week 7 in patients with moderate to severe neuropathic pain. This was a phase 3, randomized, double-blind, double-dummy parallel-group non-inferiority study conducted at 17 sites across India. Three hundred and twenty-eight adult patients with moderate to severe neuropathic pain were randomized in a ratio of 1:1 to receive a FDC of pregabalin and duloxetine or pregabalin monotherapy for 7 weeks followed by a one-week follow-up. The pregabalin-duloxetine combination was initiated at 50 plus 20 mg per day and gradually titrated to a maximum of 75mg plus 30mg twice daily. Pregabalin was initiated at 75mg/day and gradually titrated to a maximum of 150mg twice daily. The main efficacy outcome was a mean change in pain intensity at the end of 7 weeks. Two hundred and ninety-eight patients completed the study, 148 in the pregabalin-duloxetine group and 150 in the pregabalin group. The mean change in daily pain at 7 weeks was as follows: -4.49 with FDC and -4.66 with pregabalin (p<0.0001). The non-inferiority of a low-dose FDC compared to pregabalin monotherapy was demonstrated at the end of the study. The incidence of dizziness and somnolence was comparable between both treatments. A higher frequency of peripheral oedema was observed with pregabalin monotherapy than in the FDC group (p>0.05). A FDC of low doses of pregabalin and duloxetine and high dose of pregabalin monotherapy achieved similar analgesia with dizziness, and somnolence as the most frequent adverse event. CTRI/2020/09/027555.
Topics: Adult; Humans; Dizziness; Duloxetine Hydrochloride; Neuralgia; Pregabalin; Sleepiness; Double-Blind Method
PubMed: 38618021
DOI: 10.12688/f1000research.130345.1 -
Molecules (Basel, Switzerland) Apr 2022Here, we explored the possible interaction between duloxetine and SEP-363856 (SEP-856) in depression-related reactions. The results showed that oral administration of...
Here, we explored the possible interaction between duloxetine and SEP-363856 (SEP-856) in depression-related reactions. The results showed that oral administration of duloxetine showed powerful antidepressant-like effects in both the forced swimming test (FST) and the suspension tail test (TST). SEP-856 orally administered alone also exerted an antidepressant-like effect in FST and TST, especially at doses of 0.3, 1, and 10 mg/kg. In addition, duloxetine (15 mg/kg) and SEP-856 (15 mg/kg) both showed antidepressant-like effects in the sucrose preference test (SPT). Most importantly, in the above experiments, compared with duloxetine alone, the simultaneous use of duloxetine and SEP-856 caused a more significant antidepressant-like effect. It is worth noting that doses of drug combination in FST and TST did not change the motor activities of mice in the open-field test (OFT). Thus, duloxetine and SEP-856 seem to play a synergistic role in regulating depression-related behaviors and might be beneficial for refractory depression.
Topics: Animals; Antidepressive Agents; Depression; Duloxetine Hydrochloride; Hindlimb Suspension; Mice; Pyrans; Swimming
PubMed: 35566106
DOI: 10.3390/molecules27092755 -
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 Research & Management 2022There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary...
There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was "on demand" (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.
Topics: Acetaminophen; Amitriptyline; Analgesics; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Dipyrone; Duloxetine Hydrochloride; Fibromyalgia; Humans; Neuralgia; Pregabalin; Selective Serotonin Reuptake Inhibitors
PubMed: 36247103
DOI: 10.1155/2022/1217717 -
Drug Delivery Nov 2017Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral... (Comparative Study)
Comparative Study Randomized Controlled Trial
Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral bioavailability (≈50%) due to hepatic metabolism. This study aims to develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive films were prepared adopting the solvent casting method using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were evaluated for weight uniformity, drug content, surface pH, swelling index, mucoadhesion strength and drug release percentages. Accelerated stability and bioavailability studies in healthy human volunteers were also performed for the selected films. Results of the evaluation tests showed that the optimum physicochemical characters were obtained by the films prepared with 2% HPMC using 10% propylene glycol (F2 films). Accelerated stability studies revealed that DH showed proved stability throughout the experiment time. DH bioavailability from F2 films was determined and compared with that of the marketed oral capsules (Cymbalta 30 mg). The pharmacokinetic results showed that C for F2 was higher than the market product. In addition, ANOVA analysis showed that a T of F2 film was significantly lower, while, the AUC of F2 was significantly higher than that of Cymbalta capsules. The percentage relative bioavailability of DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an alternative route for the administration of DH with the possibility of improving its bioavailability.
Topics: Adhesiveness; Administration, Buccal; Animals; Biological Availability; Chemistry, Pharmaceutical; Chickens; Cross-Over Studies; Drug Delivery Systems; Drug Liberation; Duloxetine Hydrochloride; Humans; Hypromellose Derivatives; Mouth Mucosa; Polyvinyl Alcohol
PubMed: 29172829
DOI: 10.1080/10717544.2017.1402216 -
International Journal of Molecular... Aug 2023Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence...
Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.
Topics: Humans; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Cytochrome P-450 CYP1A2; Duloxetine Hydrochloride; Depression; Drug-Related Side Effects and Adverse Reactions; Polymorphism, Genetic
PubMed: 37686266
DOI: 10.3390/ijms241713459