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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 -
American Journal of Therapeutics 2019
Comparative Study
Topics: Canada; Depression; Diabetic Neuropathies; Duloxetine Hydrochloride; Europe; Humans; Medication Adherence; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Serotonin and Noradrenaline Reuptake Inhibitors; United States
PubMed: 29419534
DOI: 10.1097/MJT.0000000000000737 -
Systematic Reviews Mar 2023Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Painful diabetic peripheral neuropathy (PDPN) is a key concern in clinical practice. In this systematic review and meta-analysis, we compared duloxetine and placebo treatments in terms of their efficacy and safety in patients with PDPN.
METHODS
Following the PRISMA guidelines, we searched the Cochrane Library, PubMed, and Embase databases for relevant English articles published before January 11, 2021. Treatment efficacy and safety were assessed in terms of pain improvement, patient-reported health-related performance, and patients' quality of life.
RESULTS
We reviewed a total of 7 randomized controlled trials. Regarding pain improvement, duloxetine was more efficacious than placebo (mean difference [MD] - 0.89; 95% confidence interval [CI] - 1.09 to - 0.69; P < .00001). Furthermore, duloxetine significantly improved the patients' quality of life, which was assessed using the Clinical Global Impression severity subscale (MD - 0.48; 95% CI - 0.61 to - 0.36; P < .00001), Patient Global Impression of Improvement scale (MD - 0.50; 95% CI - 0.64 to - 0.37; P < .00001), and European Quality of Life Instrument 5D version (MD 0.04; 95% CI 0.02 to 0.07; P = .0002). Severe adverse events were rare, whereas nausea, somnolence, dizziness, fatigue, constipation, and decreased appetite were common; approximately, 12.6% of all patients dropped out because of the common symptoms.
CONCLUSIONS
Duloxetine is more efficacious than placebo treatments in patients with PDPN. The rarity of severe adverse events indicates that duloxetine is safe. When a 60-mg dose is insufficient, 120 mg of duloxetine may improve PDPN symptoms. Our findings may help devise optimal treatment strategies for PDPN.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021225451.
Topics: Humans; Duloxetine Hydrochloride; Diabetic Neuropathies; Quality of Life; Randomized Controlled Trials as Topic; Pain; Diabetes Mellitus
PubMed: 36945033
DOI: 10.1186/s13643-023-02185-6 -
Biomedicine & Pharmacotherapy =... Oct 2023Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive...
The antidepressant drugs vortioxetine and duloxetine differentially and sex-dependently affect animal well-being, cognitive performance, cardiac redox status and histology in a model of osteoarthritis.
Osteoarthritis represents a leading cause of disability with limited treatment options. Furthermore, it is frequently accompanied by cardiovascular and cognitive disorders, which can be exacerbated by osteoarthritis or drugs used for its treatment. Here, we examined the behavioral and cardiac effects of the novel antidepressant vortioxetine in an osteoarthritis model, and compared them to duloxetine (an established osteoarthritis treatment). Osteoarthritis was induced in male and female rats with an intraarticular sodium-monoiodoacetate injection. Antidepressants were orally administered for 28 days following induction. During this period the acetone, burrowing and novel-object-recognition tests (NORT) were used to assess the effects of antidepressants on pain hypersensitivity (cold allodynia), animal well-being and cognitive performance, respectively. Following behavioral experiments, heart muscles were collected for assessment of redox status/histology. Antidepressant treatment dose-dependently reduced cold allodynia in rats with osteoarthritis. Duloxetine (but not vortioxetine) depressed burrowing behavior in osteoarthritic rats in a dose-related manner. Osteoarthritis induction reduced cognitive performance in NORT, which was dose-dependently alleviated by vortioxetine (duloxetine improved performance only in female rats). Furthermore, duloxetine (but not vortioxetine) increased oxidative stress parameters in the heart muscles of female (but not male) rats and induced histological changes in cardiomyocytes indicative of oxidative damage. Vortioxetine displayed comparable efficacy to duloxetine in reducing pain hypersensitivity. Furthermore, vortioxetine (unlike duloxetine) dose-dependently improved cognitive performance and had no adverse effect on burrowing behavior (animal surrogate of well-being) and cardiac redox status/histology. Our results indicate that vortioxetine could be a potential osteoarthritis treatment (with better characteristics compared to duloxetine).
Topics: Female; Animals; Rats; Duloxetine Hydrochloride; Vortioxetine; Hyperalgesia; Antidepressive Agents; Myocytes, Cardiac; Hypersensitivity; Osteoarthritis; Cognition
PubMed: 37657261
DOI: 10.1016/j.biopha.2023.115360 -
Expert Review of Neurotherapeutics Feb 2009Generalized anxiety disorder (GAD) is a relatively prevalent and disabling condition. Duloxetine, an inhibitor of both serotonin and norepinephrine, was approved by the... (Review)
Review
Generalized anxiety disorder (GAD) is a relatively prevalent and disabling condition. Duloxetine, an inhibitor of both serotonin and norepinephrine, was approved by the US FDA in 2007 for the treatment of GAD. Short-term efficacy of duloxetine in dosages of 60-120 mg/day has been established in four double-blind, placebo-controlled trials of 9-10 weeks duration. Duloxetine has also been found to meet rigorous criteria for noninferiority in comparison with venlafaxine in GAD. Duloxetine has shown superiority on measures of functioning and quality of life and, compared with placebo treatment, it reduces painful physical symptoms common in GAD patients. Continuation treatment for acute treatment responders was found to prevent relapse of GAD to a significantly greater degree than placebo. In all acute and long-term trials, duloxetine was well-tolerated. This body of research suggests that duloxetine should be one of the options considered as a first-line treatment for GAD.
Topics: Adrenergic Uptake Inhibitors; Anxiety Disorders; Clinical Trials as Topic; Duloxetine Hydrochloride; Humans; Thiophenes
PubMed: 19210191
DOI: 10.1586/14737175.9.2.155 -
Fundamental & Clinical Pharmacology Dec 2022Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases...
Depression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases the possibility of drug interaction. Simultaneously compare the effects of duloxetine and fluoxetine on metoprolol metabolism, and provide evidence-based guidance for medication safety. Sprague-Dawley rats were randomly divided into three groups: group A (10.3 mg/kg metoprolol alone), group B (10.3 mg/kg metoprolol + 6.2 mg/kg fluoxetine), and group C (10.3 mg/kg metoprolol + 6.2 mg/kg duloxetine). Tail vein blood was collected and subjected to the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) detection. Moreover, in vitro inhibition of fluoxetine and duloxetine were assessed by incubating liver microsomes and CYP2D6.1 with metoprolol. In in vivo study, the administration of fluoxetine or duloxetine significantly increased the AUC and AUC of metoprolol (P < 0.05). Differences between fluoxetine and duloxetine in plasma concentration were also investigated, and their pharmacokinetic parameters such as AUC and AUC were significantly distinct (P < 0.05). In vitro, fluoxetine and duloxetine inhibited the metabolism of metoprolol via mixed competitive mechanism of cytochrome P450. IC values of fluoxetine and duloxetine were 12.86 and 2.51 μM, respectively. Moreover, the metabolism rate of metoprolol was inhibited to 19.62% and 17.14% in recombinant human CYP2D6.1 by fluoxetine and duloxetine, respectively. Duloxetine showed a more significant inhibitory potential compared to fluoxetine in vitro, but the main pharmacokinetic parameters of fluoxetine and duloxetine revealed differences in inhibiting metoprolol metabolism in vivo.
Topics: Rats; Animals; Humans; Fluoxetine; Metoprolol; Duloxetine Hydrochloride; Cytochrome P-450 CYP2D6; Chromatography, Liquid; Tandem Mass Spectrometry; Rats, Sprague-Dawley
PubMed: 35510497
DOI: 10.1111/fcp.12795 -
BMC Musculoskeletal Disorders May 2021Previous studies have demonstrated the efficacy of duloxetine in reducing postoperative pain and opioid consumption. However, the effect of duloxetine on total hip... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have demonstrated the efficacy of duloxetine in reducing postoperative pain and opioid consumption. However, the effect of duloxetine on total hip arthroplasty (THA) remains unclear. The objective of this study was to assess the efficacy of oral duloxetine in THA.
METHODS
We enrolled 96 patients in this randomized controlled trial. These patients were randomized (1,1) to either the duloxetine group or the placebo group and received daily doses of 60 mg duloxetine or placebo, respectively, from 2 d pre-operation to 14 d after surgery. The primary outcome was pain severity upon movement measured by a visual analogue scale (VAS). The secondary outcomes included VAS scores for resting pain, morphine consumption, Harris Hip Score, patient satisfaction at discharge, length of postoperative hospital stay, and adverse events.
RESULTS
Patients in the duloxetine group had significantly lower pain severity scores upon movement within 3 postoperative weeks (p < 0.05) while none of the differences met the minimum clinically important difference (MCID). Moreover, patients in the duloxetine group performed better in terms of resting pain (in 3 weeks after surgery), morphine requirements, and satisfaction level at discharge (all p < 0.05). There was no difference between groups in the prevalence of adverse events.
CONCLUSIONS
Although it did not result in a clinically meaning reduction in pain after total hip arthroplasty, perioperative administration of 60 mg of duloxetine daily significantly alleviated pain in the postoperative 3 weeks and morphine requirements during the postoperative 48 h. Therefore, duloxetine still shows promise in optimizing the multimodal pain-management protocols in total hip arthroplasty.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2000033606 , 06/06/2020.
Topics: Analgesics; Arthroplasty, Replacement, Hip; Double-Blind Method; Duloxetine Hydrochloride; Humans; Prospective Studies
PubMed: 34049519
DOI: 10.1186/s12891-021-04377-4 -
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 -
Duloxetine Attenuates Paclitaxel-Induced Peripheral Nerve Injury by Inhibiting p53-Related Pathways.The Journal of Pharmacology and... Jun 2020Paclitaxel (PTX) is an antineoplastic drug extracted from the species, and peripheral neuropathy is a common side effect. Paclitaxel-induced peripheral neuropathy...
Paclitaxel (PTX) is an antineoplastic drug extracted from the species, and peripheral neuropathy is a common side effect. Paclitaxel-induced peripheral neuropathy (PIPN) seriously affects patient quality of life. Currently, the mechanism of PIPN is still unknown, and few treatments are recognized clinically. Duloxetine is recommended as the only potential treatment of chemotherapy-induced peripheral neuropathy (CIPN) by the American Society of Clinical Oncology. However, this guidance lacks a theoretical basis and experimental evidence. Our study suggested that duloxetine could improve PIPN and provide neuroprotection. We explored the potential mechanisms of duloxetine on PIPN. As a result, duloxetine acts by inhibiting poly ADP-ribose polymerase cleavage (PARP) and tumor suppressor gene p53 activation and regulating apoptosis regulator the Bcl2 family to reverse PTX-induced oxidative stress and apoptosis. Taken together, the present study shows that using duloxetine to attenuate PTX-induced peripheral nerve injury and peripheral pain may provide new clinical therapeutic targets for CIPN. SIGNIFICANCE STATEMENT: This study reported that duloxetine significantly alleviates neuropathic pain induced by paclitaxel and is related to poly ADP-ribose polymerase (PARP), tumor suppressor gene p53, and apoptosis regulator the Bcl2 family. Our findings thus not only provide important guidance to support duloxetine to become the first standard chemotherapy-induced peripheral neuropathy (CIPN) drug but also will find potential new targets and positive control for new CIPN drug development.
Topics: Animals; Apoptosis; Cell Line, Tumor; Duloxetine Hydrochloride; Humans; Mice; Mice, Inbred C57BL; Oxidative Stress; Paclitaxel; Peripheral Nerve Injuries; Rats; Rats, Sprague-Dawley; Signal Transduction; Tumor Suppressor Protein p53
PubMed: 32238452
DOI: 10.1124/jpet.120.265082 -
Internal Medicine (Tokyo, Japan) Apr 2022Duloxetine is widely used for pain control and depressive syndromes. One of its potential side effects is syndrome of inappropriate secretion of antidiuretic hormone...
Duloxetine is widely used for pain control and depressive syndromes. One of its potential side effects is syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Duloxetine-induced SIADH causes hyponatremia, which leads to a variety of symptoms and has previously been reported in the elderly. In the present case, we experienced a case of the rapid onset of SIADH in a super-elderly woman receiving low-dose duloxetine. Elderly patients tend to have lower duloxetine doses and an earlier onset than non-elderly patients. When hyponatremia occurs after duloxetine administration, duloxetine-induced SIADH should be considered, especially in high-risk elderly patients, regardless of the duloxetine dose or duration of treatment.
Topics: Aged; Duloxetine Hydrochloride; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Middle Aged; Vasopressins
PubMed: 34511565
DOI: 10.2169/internalmedicine.7722-21