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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 -
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 -
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 -
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 -
Journal of Affective Disorders May 2016Vortioxetine is approved for the treatment of major depressive disorder and differs from other antidepressants in terms of its pharmacodynamic profile. Given the limited... (Review)
Review
Vortioxetine for major depressive disorder: An indirect comparison with duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, using number needed to treat, number needed to harm, and likelihood to be helped or harmed.
BACKGROUND
Vortioxetine is approved for the treatment of major depressive disorder and differs from other antidepressants in terms of its pharmacodynamic profile. Given the limited number of head-to-head studies comparing vortioxetine with other antidepressants, indirect comparisons using effect sizes observed in other trials can be helpful to discern potential differences in clinical outcomes.
METHODS
Data sources were the clinical trial reports for the pivotal short-term double-blind trials for vortioxetine and from publicly available sources for the pivotal short-term double-blind trials for two commonly used generic serotonin specific reuptake inhibitor antidepressants (sertraline, escitalopram), two commonly used generic serotonin-norepinephrine reuptake inhibitor antidepressants (venlafaxine, duloxetine), and two recently introduced branded antidepressants (vilazodone, levomilnacipran). Response was the efficacy outcome of interest, defined as a≥50% reduction from baseline on the Montgomery-Asberg Depression Rating Scale or Hamilton Depression Rating Scale. The tolerability outcome of interest was discontinuation because of an adverse event. Number needed to treat (NNT) and number needed to harm (NNH) for these outcomes vs. placebo were calculated, as well as likelihood to be helped or harmed (LHH) to contrast efficacy vs. tolerability.
RESULTS
The analysis included 8 studies for duloxetine, 3 studies for escitalopram, 5 studies for levomilnacipran, 1 study for sertraline, 4 studies for venlafaxine, 2 studies for vilazodone, and 11 studies for vortioxetine. NNTs for response vs. placebo were 6 (95% CI 5-8), 7 (5-11), 10 (8-16), 6 (4-13), 6 (5-9), 8 (6-16), and 9 (7-11), respectively. NNHs for discontinuation because of an adverse event vs. placebo were 25 (17-51), 31 (19-92), 19 (14-27), 7 (5-12), 8 (7-11), 27 (15-104), and 43 (28-91), respectively. LHH values contrasting response vs. discontinuation because of an adverse event were 4.3, 4.6, 1.8, 1.2, 1.4, 3.3, and 5.1 respectively.
LIMITATIONS
Subjects were all participants in carefully designed and executed clinical trials and may not necessarily reflect patients in clinical settings who may have complex psychiatric and non-psychiatric comorbidities. The measured outcomes come from different studies and thus comparisons are indirect.
CONCLUSIONS
Vortioxetine demonstrates similar efficacy to that observed for duloxetine, escitalopram, levomilnacipran, sertraline, venlafaxine, and vilazodone, however overall tolerability as measured by discontinuation because of an adverse event differs. Vortioxetine is 5.1 times more likely to be associated with response than discontinuation because of an adverse event when compared to placebo.
Topics: Adult; Antidepressive Agents; Citalopram; Depressive Disorder, Major; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome; Venlafaxine Hydrochloride; Vilazodone Hydrochloride
PubMed: 26938965
DOI: 10.1016/j.jad.2016.02.042 -
International Journal of Clinical... Nov 2021In patients with diabetes mellitus, painful diabetic peripheral neuropathy (PDPN) is a frequent complication and can cause poor quality of life. We compared the efficacy... (Meta-Analysis)
Meta-Analysis
Comparison of efficacy and safety of gabapentin and duloxetine in painful diabetic peripheral neuropathy: A systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
In patients with diabetes mellitus, painful diabetic peripheral neuropathy (PDPN) is a frequent complication and can cause poor quality of life. We compared the efficacy and safety of duloxetine with those of gabapentin in patients with PDPN through a systematic review and meta-analysis of randomised controlled trials.
MATERIALS AND METHODS
PubMed, Embase and the Cochrane Library were searched for eligible studies published from database inception to January 2021. Visual Analogue Scale (VAS), sleep interference score, Clinical Global Impression of Change (CGIC), Patient Global Impression of Change (PGIC), Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathic Examination (DNE) score, Neuropathic Disability Score (NDS) and side effects were used to compare duloxetine and gabapentin in patients with PDPN.
RESULTS
Three eligible randomised controlled trials involving 290 patients were included. No significant differences were observed between patients receiving duloxetine and gabapentin with respect to VAS (mean change difference = -1.23, 95% CI, -6.09 to 3.62; P = .62), sleep interference score (mean change difference = 0.42, 95% CI, -0.15 to 1.00; P = .15), CGIC (mean difference = 0.04, 95% CI, -0.11 to 0.20; P = .60), PGIC (mean difference= 0.24, 95% CI, -0.13 to 0.60; P = .21), DNS (mean change difference = 0.14, 95% CI, -0.35 to 0.63; P = .58), DNE (mean change difference = 0.26, 95% CI, -0.35 to 0.86; P = .41) and NDS (mean change difference = 0.30, 95% CI, -0.02 to 0.63; P = .07).
CONCLUSIONS
No significant differences were observed in the efficacy of duloxetine and gabapentin when treating patients with PDPN.
Topics: Analgesics; Diabetes Mellitus; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 34171158
DOI: 10.1111/ijcp.14576 -
Expert Review of Clinical Pharmacology Feb 2022The identification of the most effective therapy for patients with fibromyalgia (FM) remains controversial. Thus, we conducted a Bayesian network meta-analysis to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The identification of the most effective therapy for patients with fibromyalgia (FM) remains controversial. Thus, we conducted a Bayesian network meta-analysis to compare several drugs employed as pharmacological management for FM.
AREAS COVERED
The following databases were accessed in October 2021: PubMed, Google Scholar, Embase, and Scopus. All the randomized clinical trials (RCTs) that compare two or more pharmacological management for fibromyalgia were accessed. Only studies involving a minimum of 10 patients with a length of follow-up longer than 4 weeks were included. The data from the fibromyalgia impact questionnaire (FIQ) and the physical and mental subscales short form 36 (SF36) were extracted at last follow-up. Additionally, the number of adverse events leading to the study of discontinuation was extracted. The compounds of interests were duloxetine, pregabalin, fluoxetine, gabapentin, milnacipran, trazodone, placebo, nortriptyline, IGF-I, amitriptyline, and the combination of fluoxetine and amitriptyline, pregabalin, and trazodone.
EXPERT OPINION
According to published evidence, pregabalin, and duloxetine evidenced the greatest improvement of the FIQ and SF36 Physical and Mental subscales, along with the lowest rate of adverse events leading to study discontinuation. The results must be interpreted in light of possible adverse events associated with the use of these drugs.
Topics: Analgesics; Duloxetine Hydrochloride; Fibromyalgia; Gabapentin; Humans; Network Meta-Analysis; Pregabalin
PubMed: 35184627
DOI: 10.1080/17512433.2022.2044792 -
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 -
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 -
Clinical Drug Investigation Jul 2016Vortioxetine and duloxetine are two new antidepressant drugs that have been used clinically in the treatment of major depressive disorder (MDD). The objectives of this... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Vortioxetine and duloxetine are two new antidepressant drugs that have been used clinically in the treatment of major depressive disorder (MDD). The objectives of this meta-analysis were to evaluate the efficacy and tolerability of vortioxetine compared with duloxetine in MDD.
METHODS
Randomized controlled trials (RCTs) published in PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were systematically reviewed to compare vortioxetine with duloxetine in terms of efficacy and tolerability in patients with MDD. Results were expressed as the risk ratio (RR) with 95 % confidence intervals (CIs), and weighted mean difference (WMD). Pooled estimates were calculated by using a fixed-effects model or a randomized-effects model, depending on the heterogeneity among studies.
RESULTS
A total of five RCTs involving 2287 patients met the inclusion criteria and were included in this meta-analysis. Pooled results showed that duloxetine was associated with a higher response rate than vortioxetine, as well as showing a similar remission rate with vortioxetine. The changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS), 24-item Hamilton Rating Scale for Depression (HAM-D24), Clinical Global Impression-Improvement scale (CGI-I), CGI-Severity scale (CGI-S), Sheehan Disability Scale (SDS), and Hamilton Anxiety Rating Scale (HAM-A) scores were significantly greater in the duloxetine group than in the vortioxetine group. The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group.
CONCLUSION
Duloxetine was more effective but less well-tolerated than vortioxetine in MDD. Considering the potential limitations of this meta-analysis, more large-scale RCTs are needed to confirm these findings.
Topics: Antidepressive Agents; Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Piperazines; Randomized Controlled Trials as Topic; Sulfides; Treatment Outcome; Vortioxetine
PubMed: 27067232
DOI: 10.1007/s40261-016-0396-9