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Dental Clinics of North America Oct 2023A patient with a past medical history significant for fibromyalgia presents for an incisional oral biopsy. The condition is being managed pharmacologically with... (Review)
Review
A patient with a past medical history significant for fibromyalgia presents for an incisional oral biopsy. The condition is being managed pharmacologically with duloxetine and ibuprofen. Given the patient's medical condition and medications, specific considerations were placed on chair positioning, muscle pain and tenderness, and achieving hemostasis through local measures. The patient was advised to follow up in 2 weeks for postoperative evaluation.
Topics: Humans; Fibromyalgia; Biopsy; Duloxetine Hydrochloride; Ibuprofen
PubMed: 37714615
DOI: 10.1016/j.cden.2023.06.002 -
Pain Practice : the Official Journal of... Sep 2023Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral duloxetine, when given perioperatively, is any better than a placebo in managing postoperative pain. Effects of duloxetine on postoperative pain scores, time to first rescue analgesia, postoperative rescue analgesia consumption, side effects attributable to duloxetine, and patient satisfaction profile were assessed.
METHOD
MEDLINE, Web of Science, EMBASE, Scholar Google, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched with keywords including "Duloxetine" AND "postoperative pain", "Duloxetine" AND "acute pain" and with "Duloxetine" till October 2022. This meta-analysis included randomized clinical trials in which perioperative duloxetine 60 mg per oral was administered not more than 7 days before surgery and for at least 24 after surgery but not more than 14 days after surgery. All RCTs in which the comparator is placebo and outcomes related to analgesic efficacy like pain scores, opioid consumption, and side effects of duloxetine until 48 h postoperatively were included. Data were extracted from the studies and a risk of bias summary was formed using the Cochrane Collaboration tool. Effect sizes were given as standardized mean differences for continuous outcomes and risk ratios (RR) by the Mantel-Haenszel test for the categorical outcome. Confirmation of publication bias was done by Egger's regression test (p < 0.05). If publication bias or heterogeneity was detected, the trim-and-fill method was used to calculate the adjusted effect size. Sensitivity analysis was done by leaving one out method after excluding the study with a high risk of bias. Subgroup analysis was done based on the type of surgery and gender. The study was prospectively registered in the PROSPERO under the registration number CRD42019139559.
FINDINGS
29 studies with 2043 patients met the inclusion criteria and were reviewed for this meta-analysis. Postoperative pain scores at 24 h [Std. Mean Difference (95% CI); -0.69 (-1.07, -0.32)] and at 48 h [-1.13 (-1.68, -0.58)] are significantly less with duloxetine (p-value < 0.05). Time to first rescue analgesia was significantly more in patients where duloxetine was administered [1.27 (1.10, 1.45); p-value > 0.05]. Opioid consumption up to 24 h [-1.82 (-2.46, -1.18)] and 48 h [-2.48 (-3.46, -1.50)] was significantly less (p-value < 0.05) in patients who received duloxetine. Complications and recovery profiles were similar in patients receiving either duloxetine or a placebo.
INTERPRETATION
Based on GRADE findings, we conclude that there is low to moderate evidence to advocate the use of duloxetine for managing postoperative pain. Further trials are needed to replicate or refute these results based on robust methodology.
Topics: Humans; Analgesics, Opioid; Pain Management; Duloxetine Hydrochloride; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37246352
DOI: 10.1111/papr.13253 -
BMC Pulmonary Medicine Aug 2023Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough.
METHODS AND ANALYSIS
This is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test.
DISCUSSION
This study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition.
TRIAL REGISTRATION
Our study was registered in the Chinese Clinical Trials Register ( www.chictr.org.cn/ ) (ChiCTR2000037429) in 28/08/2020.
Topics: Humans; Duloxetine Hydrochloride; Cough; Tablets, Enteric-Coated; Quality of Life; Prospective Studies; Pain; Double-Blind Method; Treatment Outcome
PubMed: 37533019
DOI: 10.1186/s12890-023-02575-5 -
Drug Metabolism and Pharmacokinetics Aug 2023The objectives of this analysis were to characterize the pharmacokinetics of duloxetine in Japanese pediatric patients aged 9-17 years with major depressive disorder...
The objectives of this analysis were to characterize the pharmacokinetics of duloxetine in Japanese pediatric patients aged 9-17 years with major depressive disorder (MDD) and to explore potential intrinsic factors affecting its pharmacokinetics. A population pharmacokinetic (PK) model was developed with plasma steady-state duloxetine concentrations from Japanese pediatric patients with MDD in an open-label long-term extension trial in Japan (ClinicalTrials.gov Identifier: NCT03395353). Duloxetine pharmacokinetics in Japanese pediatric patients was well described by a one-compartment model with first-order absorption. The population mean estimates of CL/F and V/F of duloxetine were 81.4 L/h and 1170 L, respectively. Patient intrinsic factors were assessed for their potential influence on duloxetine apparent clearance (CL/F). Only sex was identified as a statistically significant covariate of duloxetine CL/F. Duloxetine pharmacokinetic parameters and model-predicted duloxetine concentrations at steady state in the Japanese pediatric population were compared with those in Japanese adults. The mean duloxetine CL/F in pediatrics is slightly higher than adults, it is, however, expected that comparable steady-state duloxetine exposure in pediatric patients can be achieved with the approved dose regimen for adults. The population PK model provides useful information to understand the pharmacokinetic characteristics of duloxetine for Japanese pediatric patients with MDD. CLINICALTRIALS.GOV IDENTIFIER: NCT03395353.
Topics: Adult; Child; Humans; Depressive Disorder, Major; Duloxetine Hydrochloride; East Asian People; Japan
PubMed: 37244205
DOI: 10.1016/j.dmpk.2023.100496 -
Trials May 2024Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and...
Duloxetine and cognitive behavioral therapy with phone-based support for the treatment of chronic musculoskeletal pain: study protocol of the PRECICE randomized control trial.
BACKGROUND
Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT.
METHODS
Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of three treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI, and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment.
DISCUSSION
This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills, thereby enhancing treatment outcomes.
TRIAL REGISTRATION
NCT04395001 ClinicalTrials.gov. Registered on May 15, 2020.
Topics: Duloxetine Hydrochloride; Humans; Cognitive Behavioral Therapy; Chronic Pain; Musculoskeletal Pain; Randomized Controlled Trials as Topic; Treatment Outcome; Combined Modality Therapy; Pain Measurement; Telephone; Motivational Interviewing; Analgesics; Time Factors; Internet-Based Intervention; Pain Management; Adaptation, Psychological; Adult
PubMed: 38762720
DOI: 10.1186/s13063-024-08158-x -
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 Prostate Feb 2024Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and duloxetine are used to manage post-RARP UI, but their efficacy remains uncertain. We aimed to investigate the efficacy of PFMT and duloxetine in promoting urinary continence recovery (UCR) after RARP.
METHODS
A randomized controlled trial involving patients with urine leakage after RARP from May 2015 to February 2018. Patients were randomized into 1 of 4 arms: (1) PFMT-biofeedback, (2) duloxetine, (3) combined PFMT-biofeedback and duloxetine, (4) control arm. PFMT consisted of pelvic muscle exercises conducted with electromyographic feedback weekly, for 3 months. Oral duloxetine was administered at bedtime for 3 months. The primary outcome was prevalence of continence at 6 months, defined as using ≤1 security pad. Urinary symptoms and QoL were assessed by using a visual analogue scale, and validated questionnaires.
RESULTS
From the 240 patients included in the trial, 89% of patients completed 1 year of follow-up. Treatment compliance was observed in 88% (92/105) of patients receiving duloxetine, and in 97% (104/107) of patients scheduled to PFMT-biofeedback sessions. In the control group 96% of patients had achieved continence at 6 months, compared with 90% (p = 0.3) in the PMFT-biofeedback, 73% (p = 0.008) in the duloxetine, and 69% (p = 0.003) in the combined treatment arm. At 6 months, QoL was classified as uncomfortable or worse in 17% of patients in the control group, compared with 44% (p = 0.01), 45% (p = 0.008), and 34% (p = 0.07), respectively. Complete preservation of neurovascular bundles (NVB) (OR: 2.95; p = 0.048) was the only perioperative intervention found to improve early UCR.
CONCLUSIONS
PFMT-biofeedback and duloxetine demonstrated limited impact in improving UCR after RP. Diligent NVB preservation, along with preoperative patient and disease characteristics, are the primary determinants for early UCR.
Topics: Male; Humans; Quality of Life; Duloxetine Hydrochloride; Pelvic Floor; Treatment Outcome; Urinary Incontinence; Prostatectomy
PubMed: 37904330
DOI: 10.1002/pros.24634 -
Chirality Mar 2024Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the... (Review)
Review
Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.
Topics: Duloxetine Hydrochloride; Ofloxacin; Stereoisomerism; Electrophoresis, Capillary
PubMed: 38454837
DOI: 10.1002/chir.23661 -
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 -
Contemporary Clinical Trials Jun 2024Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can...
BACKGROUND
Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination.
METHODS
This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires.
CONCLUSION
The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www.
CLINICALTRIALS
gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.
Topics: Adult; Female; Humans; Male; Middle Aged; Antidepressive Agents; Anxiety; Combined Modality Therapy; Depression; Duloxetine Hydrochloride; Patient Education as Topic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38604496
DOI: 10.1016/j.cct.2024.107524