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Revista Da Associacao Medica Brasileira... Mar 2022This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This study aimed to investigate the effects of duloxetine and pregabalin primarily on pain and functional status in patients with knee osteoarthritis and secondarily on quality of life, depression, anxiety, and sleep disturbance.
METHODS
A total of 66 patients with knee osteoarthritis were randomized to use duloxetine or pregabalin. Patients were evaluated by Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36, Beck Depression Inventory, Beck Anxiety Inventory, and Pittsburg Sleep Quality Index before the treatment and after 4 and 12 weeks of treatment.
RESULTS
Improvements occurred in Visual Analog Scale, Neuropathic Pain Diagnostic Questionnaire, Western Ontario and McMaster University Osteoarthritis Index, Short Form-36 (with an exception of the mental health subgroup scores in duloxetine-treated group), Beck Depression Inventory, and Beck Anxiety Inventory scores in both groups from 4 weeks after baseline. Pittsburg Sleep Quality Index total scores and SF-36 mental health subgroup scores started to improve on the 4th and 12th weeks in pregabalin- and duloxetine-treated groups, respectively.
CONCLUSION
Osteoarthritis pain, a complex outcome with nociceptive and neuropathic components, leads to central sensitization in a chronic phase. Using centrally acting drugs in the control of pain and associated symptoms would increase the probability of treatment success.
Topics: Duloxetine Hydrochloride; Humans; Neuralgia; Osteoarthritis, Knee; Pregabalin; Quality of Life; Treatment Outcome
PubMed: 35442367
DOI: 10.1590/1806-9282.20211047 -
Fukushima Journal of Medical Science Apr 2022Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the... (Review)
Review
Pancreatic cancer (PC) is a lethal disease where most tumors are too advanced at diagnosis for resection, leaving chemotherapy as the mainstay of treatment. Although the prognosis of unresectable PC is poor, it has been dramatically improved by new chemotherapy treatments, such as the combination of 5-fluorouracil, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) or gemcitabine plus nab-paclitaxel. However, as oxaliplatin and paclitaxel are common neurotoxic drugs, chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse effect of both treatments. As there are no agents recommended in the ASCO guidelines, we review the methods used to treat CIPN caused by PC treatment. The efficacy of duloxetine was observed in a large randomized controlled trial (RCT). In addition, pregabalin was more effective than duloxetine for CIPN in two RCTs. Although duloxetine and pregabalin can be effective for CIPN, they have several side effects. Therefore, the choice between the two drugs should be determined according to effect and tolerability. Mirogabalin is also used in patients with PC and there is hope it will yield positive outcomes when treating CIPN in the future.
Topics: Antineoplastic Agents; Duloxetine Hydrochloride; Humans; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Peripheral Nervous System Diseases; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 35197393
DOI: 10.5387/fms.2021-32 -
The Journal of Clinical Psychiatry Aug 2015Cognitive functioning is a symptom of major depressive disorder (MDD) that deserves particular attention by clinicians and researchers. Despite the fact that cognitive... (Review)
Review
Cognitive functioning is a symptom of major depressive disorder (MDD) that deserves particular attention by clinicians and researchers. Despite the fact that cognitive dysfunction represents a symptom of MDD as well as a functional outcome measure, cognition has been insufficiently investigated in antidepressant trials. While, until recently, few placebo-controlled trials have measured cognition in MDD, those examples which did have consisted of older adults. Of agents tested thus far in placebo-controlled trials (citalopram, duloxetine, vortioxetine), only the latter has been studied in patients aged 18-65, and only the latter has been shown to be superior to placebo in improving measures of executive functioning and to do so across adult age groups. Both duloxetine and vortioxetine appear to result in greater improvements than placebo in immediate and delayed memory. Clinicians who wish to improve the psychosocial recovery of patients with MDD should be familiar with studies of new options for treatment.
Topics: Adult; Citalopram; Cognition Disorders; Depressive Disorder, Major; Duloxetine Hydrochloride; Executive Function; Humans; Middle Aged; Piperazines; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sulfides; Vortioxetine
PubMed: 26335095
DOI: 10.4088/JCP.13086tx5c -
Journal of Clinical Anesthesia Aug 2020Duloxetine administered during the acute perioperative period has been associated with lesser postoperative pain and analgesic consumption. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duloxetine administered during the acute perioperative period has been associated with lesser postoperative pain and analgesic consumption.
STUDY OBJECTIVES
The study aimed to quantify the pooled effects of duloxetine on postoperative pain, analgesic consumption, and side-effects in the first 48 postoperative (PO) hours.
DESIGN
Systematic review with meta-analysis.
SETTING
Postoperative pain management.
PATIENTS
Adult patients undergoing elective surgery. Search strategy and study selection. Medline, Cochrane, EMBASE, CENTRAL, and Web of Science were searched without language restrictions for prospective, parallel randomized controlled trials comparing duloxetine to placebo for the management of postoperative pain in adult patients.
MEASUREMENTS
Pain scores (11-point scales), opioid consumption (i.v. morphine equivalents), and frequency of side-effects were compared between duloxetine and placebo. Effect sizes were summarized as mean differences (MD), standardized mean differences (SMD) or risk ratios (RR) with the respective 95% confidence intervals (95% CI). Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were used to classify the quality of evidence.
RESULTS
Thirteen studies were included. Duloxetine decreased pain at 24 h (MD = -0.66 points; 95% CI = -1.14 to -0.19 points; SMD = -0.59; 95% CI = -1.06 to -0.12; p = 0.01; I2 = 88%), and at 48 PO hours (MD = -0.90 points; 95% CI = -1.54 to -0.26 points; SMD = -0.66; 95% CI = -0.94 to -0.38; p = 0.01; I2 = 93%); and opioid consumption at 24 PO hours (MD = -8.21 mg; 95% CI = -13.32 mg to -3.10 mg; SMD = -2.17; 95% CI = -3.10 to -1.24; p < 0.001; I2 = 95%), and at 48 PO hours (MD = 7.71 mg; 95% CI = -13.86 mg to -1.56 mg; SMD = -2.13; 95% CI = -3.51 to -0.75; p = 0.02; I2 = 97%). Duloxetine did not affect the prevalence of postoperative nausea and/or vomiting (PONV) pruritus, headache or dizziness. High inter-study heterogeneity and within-study bias resulted in very-low quality of evidence for the primary outcomes.
CONCLUSIONS
Although statistically significant effects of duloxetine were found on postoperative pain and opioid consumption during the first 48 postoperative hours, the effect sizes were below the expected minimal clinically relevant differences. Also, high risk-of-bias and inter-study heterogeneity caused the very-low quality of evidence (GRADE). We conclude that the currently available evidence does not support the clinical use of duloxetine for the management of acute postoperative pain.
Topics: Adult; Analgesics, Opioid; Duloxetine Hydrochloride; Humans; Pain Measurement; Pain, Postoperative; Prospective Studies
PubMed: 32179396
DOI: 10.1016/j.jclinane.2020.109785 -
Anesthesia and Analgesia Mar 2016Antidepressant S-duloxetine alleviates intractable pain associated with diabetic peripheral neuropathy and fibromyalgia. It also reduces both acute and persistent pain...
BACKGROUND
Antidepressant S-duloxetine alleviates intractable pain associated with diabetic peripheral neuropathy and fibromyalgia. It also reduces both acute and persistent pain in various animal models. This study addresses whether the enantiomer, R-duloxetine, and the homolog, N-methyl duloxetine, could act as analgesics and whether they block neuronal Na⁺ channels.
METHODS
The rat incision plus extension model on the dorsothoracic skin was applied to evoke postoperative mechanoallodynia and hyperalgesia, measured for 5 days postoperatively by local responses to von Frey filaments. R-Duloxetine and N-methyl duloxetine were administered systemically (intraperitoneal) or locally (subcutaneous [SC]) 1 hour before the surgery. The block of Na currents in rat neuronal GH3 cells was determined under the whole-cell configuration.
RESULTS
Ipsilateral SC injections (2 mg/0.4 mL) of R-duloxetine and N-methyl duloxetine reduced both postoperative allodynia and hyperalgesia by approximately 89% to 99% in the area under the curve of skin responses next to incision over 5 days. Systemic intraperitoneal injections at a higher dosage (10 mg) had smaller analgesic effects (reduced by approximately 53%-69%), whereas contralateral SC injections (10 mg) were ineffective. Both R-duloxetine and N-methyl duloxetine blocked neuronal Na⁺ currents, with a higher affinity for the inactivated than the resting states. In addition, both drugs elicited significant use-dependent block of Na currents when stimulated at 5 Hz.
CONCLUSIONS
R-Duloxetine and N-methyl duloxetine are highly effective against postoperative pain using the skin incision model, and they elicit both tonic and use-dependent block of neuronal Na⁺ channels. Our results suggest that R-duloxetine and N-methyl duloxetine are applicable as novel analgesics.
Topics: Analgesics; Animals; Antidepressive Agents, Second-Generation; Cell Line; Duloxetine Hydrochloride; Hyperalgesia; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Neurons; Pain, Postoperative; Patch-Clamp Techniques; Physical Stimulation; Pituitary Gland; Rats; Rats, Sprague-Dawley; Sodium Channel Blockers
PubMed: 26646348
DOI: 10.1213/ANE.0000000000001086 -
International Journal of Clinical... Feb 2024Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid consumption in patients after total hip or knee arthroplasty.
AIM
This systematic review and meta-analysis aimed to analyze pain control, opioid consumption, and associated adverse events of perioperative administration of duloxetine after total hip or knee arthroplasty.
METHOD
After being registered with PROSPERO (CRD42022323202), the databases of MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception until March 20, 2023, for randomized controlled trials (RCTs). Primary outcomes were the visual Analog Scale (VAS) pain scores at rest (rVAS) and upon ambulation (aVAS). Secondary outcomes were postoperative opioid consumption quantified as oral morphine milligram equivalents (MMEs) and adverse effects of duloxetine.
RESULTS
Nine RCTs with 806 cases were included. Duloxetine was associated with lower VAS scores at different times after surgery (24 h, two weeks, and ≥ 3 months). Compared to placebo, perioperative daily duloxetine use significantly reduced daily opioid MMEs at 24 h (standard mean deviation [SMD] -0.71, 95% confidence interval [95% CI] -1.19 to -0.24, P = 0.003), three days (SMD -1.10, 95% CI -1.70 to -0.50, P = 0.0003), and one week (SMD -1.18, 95% CI -1.99 to -0.38, P = 0.004) after surgery. The duloxetine group had a significantly lower rate of nausea (odds ratio 0.62, 95% CI [0.41 to 0.94], P = 0.02) and a higher rate of drowsiness and somnolence (odds ratio 1.87, 95% CI [1.13 to 3.07], P = 0.01) compared to the placebo group. No significant differences were observed in the rates of other adverse events.
CONCLUSION
Perioperative duloxetine significantly decreased postoperative pain and opioid consumption with good safety profiles. Further high quality designed and well-controlled randomized trials are warranted.
Topics: Humans; Analgesics, Opioid; Duloxetine Hydrochloride; Arthroplasty, Replacement, Hip; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37294475
DOI: 10.1007/s11096-023-01593-x -
Frontiers in Bioscience (Landmark... Aug 2023This study was carried out to compare the levels of inflammatory markers in the complete blood count before and after they began receiving duloxetine in patients with...
BACKGROUND
This study was carried out to compare the levels of inflammatory markers in the complete blood count before and after they began receiving duloxetine in patients with fibromyalgia syndrome (FMS).
METHODS
The patient and control groups were composed of 40 patients diagnosed with FMS in accordance with the 2016 American College of Rheumatology (ACR) criteria and 40 healthy volunteers, respectively. The data collection tools comprised the sociodemographic information form, the fibromyalgia impact questionnaire (FIQ), and the sleep hygiene index (SHI), which were used to assess patients' sociodemographic characteristics, FMS disease activity, and sleep quality, respectively. The inflammatory markers of the patient group were assessed by complete blood count before and after the duloxetine treatment and compared with those of the control group.
RESULTS
The white blood cell (WBC), neutrophil, and lymphocyte counts were significantly higher in the patient group than in the control group ( < 0.001, = 0.036 and = 0.004, respectively). Moreover, platelet distribution width (PDW) was significantly lower, whereas mean platelet volume (MPV) was significantly higher in the patient group than in the control group ( < 0.001 for both cases). In addition to patients' platelet-to-lymphocyte ratio (PLR) values, C-reactive protein (CRP) levels, and white blood cell (WBC) counts decreasing but not significantly ( = 0.083, = 0.068, and = 0.065, respectively), their neutrophil-to-lymphocyte ratio (NLR), hemoglobin (Hgb), and hematocrit (Hct) values declined substantially after commencing duloxetine treatment ( = 0.001, = 0.008, and = 0.001, respectively).
CONCLUSIONS
The significant reduction in NLR, Hgb, and Hct levels following duloxetine treatment may indicate that these parameters can be utilized as biomarkers in determining the efficacy of treatment and in the follow-up of the treatment in FMS patients.
Topics: Humans; Duloxetine Hydrochloride; Fibromyalgia; Leukocytes; Blood Platelets; Neutrophils
PubMed: 37664936
DOI: 10.31083/j.fbl2808161 -
Cancer Research Communications Nov 2022Oxaliplatin-induced peripheral neurotoxicity (OIPN) is a debilitating side effect that afflicts ~90% of patients that is initiated by OCT2-dependent uptake of...
UNLABELLED
Oxaliplatin-induced peripheral neurotoxicity (OIPN) is a debilitating side effect that afflicts ~90% of patients that is initiated by OCT2-dependent uptake of oxaliplatin in DRG neurons. The antidepressant drug duloxetine has been used to treat OIPN, although its usefulness in preventing this side effect remains unclear. We hypothesized that duloxetine has OCT2-inhibitory properties and can be used as an adjunct to oxaliplatin-based regimens to prevent OIPN. Transport studies were performed in cells stably transfected with mouse or human OCT2 and in isolated mouse DRG neurons . Wild-type and OCT2-deficient mice were used to assess effects of duloxetine on hallmarks of OIPN, endogenous OCT2 biomarkers, and the pharmacokinetics of oxaliplatin, and the translational feasibility of a duloxetine-oxaliplatin combination was evaluated in various models of colorectal cancer. We found that duloxetine potently inhibited the OCT2-mediated transport of several xenobiotic substrates, including oxaliplatin, in a reversible, concentration-dependent manner, and independent of species and cell context. Furthermore, duloxetine restricted access of these substrates to DRG neurons and prevented OIPN in wild-type mice to a degree similar to the complete protection observed in OCT2-deficient mice, without affecting the plasma levels of oxaliplatin. Importantly, the uptake and cytotoxicity of oxaliplatin in tumor cell lines and were not negatively influenced by duloxetine. The observed OCT2-targeting properties of duloxetine, combined with the potential for clinical translation, provide support for its further exploration as a therapeutic candidate for studies aimed at preventing OIPN in cancer patients requiring treatment with oxaliplatin.
SIGNIFICANCE
We found that duloxetine has potent OCT2-inhibitory properties and can diminish excessive accumulation of oxaliplatin into DRG neurons. In addition, pre-treatment of mice with duloxetine prevented OIPN without significantly altering the plasma pharmacokinetics and antitumor properties of oxaliplatin. These results suggest that intentional inhibition of OCT2-mediated transport by duloxetine can be employed as a prevention strategy to ameliorate OIPN without compromising the effectiveness of oxaliplatin-based treatment.
Topics: Humans; Mice; Animals; Oxaliplatin; Antineoplastic Agents; Duloxetine Hydrochloride; Peripheral Nervous System Diseases; Neurotoxicity Syndromes
PubMed: 36506732
DOI: 10.1158/2767-9764.crc-22-0172 -
Current Opinion in Anaesthesiology Oct 2017Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of... (Review)
Review
PURPOSE OF REVIEW
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of cancer survivors and an increasing recognition of opioid therapy limitations, there is a need for critical analysis of the literature in directing an informed and thoughtful approach for the management of painful CIPN.
RECENT FINDINGS
A PubMed search for 'chemotherapy-induced peripheral neuropathy AND pain' identifies 259 publications between 1 January 2016 and 31 March 2017. Based on review of this literature, we aim to present a clinically relevant update of painful CIPN. Notably, the use of duloxetine as a first-line agent in treatment of CIPN is confirmed. Moreover, clinical trials focus on nonpharmacologic strategies for managing painful CIPN.
SUMMARY
Despite the volume of recent publications, there are limited preventive or therapeutic strategies for CIPN supported by high-level evidence. Duloxetine remains the only pharmacologic agent with demonstrated benefit; its clinical use should be routinely considered. Moving forward, nonopioid analgesic therapies will likely play an increasing role in CIPN treatment, but further research is necessary to confirm their utility. Promising therapies include vitamin B12 supplementation, physical therapy, and various forms of neuromodulation.
Topics: Duloxetine Hydrochloride; Humans; Peripheral Nervous System Diseases; Vitamin B 12
PubMed: 28708674
DOI: 10.1097/ACO.0000000000000500 -
Journal of Child and Adolescent... Apr 2022The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Duloxetine in Children and Adolescents with Major Depressive Disorder in Japan: A Randomized Double-Blind Placebo-Controlled Clinical Trial Followed by an Open-Label Long-Term Extension Trial.
The goal of this study was to evaluate the efficacy and safety of duloxetine in children and adolescents (9-17 years of age) with major depressive disorder (MDD) in Japan. This study consists of two clinical trials. First, a 6-week, randomized double-blind placebo-controlled clinical trial (RCT) was conducted. The primary endpoint of RCT was the change in Children's Depression Rating Scale-Revised (CDRS-R) total scores from baseline. Following RCT, an open-label long-term extension trial (OLE) was conducted to investigate the longer-term safety of duloxetine for ∼1 year. In RCT, CDRS-R total score changes from baseline to 6 weeks after the start of administration (primary endpoint) were -21.03 in the duloxetine group ( = 74) and -22.42 in the placebo group ( = 74). No significant difference was observed in the primary endpoint between the groups ( = 0.5587). In addition, no significant difference was observed in secondary endpoints such as CDRS-R response rates. The proportion of patients with ≥1 treatment-emergent adverse event (TEAE) in RCT was significantly higher in the duloxetine group (78.7%) than in the placebo group (62.2%), and most were mild or moderate in severity. Changes in CDRS-R total scores during OLE, in consecutive patients from the duloxetine group in RCT ( = 63), or placebo group ( = 59) in RCT, and newly enrolled patients ( = 28), were -12.1, -11.3, and -17.8, respectively. The proportion of patients with ≥1 TEAE in OLE was 90.5%, 88.1%, and 89.3% in the respective groups, and most of them were mild or moderate in severity. Duloxetine did not show superiority to placebo in efficacy in children and adolescents with MDD in Japan. Overall reported TEAEs were consistent with the currently available duloxetine safety profile and no new safety finding was observed in the two clinical trials.
Topics: Adolescent; Antidepressive Agents; Child; Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Duloxetine Hydrochloride; Humans; Japan; Treatment Outcome
PubMed: 35319270
DOI: 10.1089/cap.2021.0104