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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 -
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 -
American Family Physician Mar 2024Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening...
Diabetic peripheral neuropathy occurs in up to 50% of patients with diabetes mellitus and increases the risk of diabetic foot ulcers and infections. Consistent screening and clear communication are essential to decrease disparities in assessment of neuropathic symptoms and diagnosis. Physicians should address underlying risk factors such as poor glycemic control, vitamin B12 deficiency, elevated blood pressure, and obesity to reduce the likelihood of developing neuropathy. First-line drug therapy for painful diabetic peripheral neuropathy includes duloxetine, gabapentin, amitriptyline, and pregabalin; however, these medications do not restore sensation to affected extremities. Evidence for long-term benefit and safety of first-line treatment options is lacking. Second-line drug therapy includes nortriptyline, imipramine, venlafaxine, carbamazepine, oxcarbazepine, topical lidocaine, and topical capsaicin. Periodic, objective monitoring of medication response is critical because patients may not obtain desired pain reduction, adverse effects are common, and serious adverse effects can occur. Opioids should generally be avoided. Nondrug therapies with low- to moderate-quality evidence include exercise and neuromodulation with spinal cord stimulation or transcutaneous electrical nerve stimulation. Peripheral transcutaneous electrical nerve stimulation is well tolerated and inexpensive, but benefits are modest. Other treatments, such as acupuncture, alpha-lipoic acid, acetyl-L-carnitine, cannabidiol, and onabotulinumtoxinA need further study in patients with diabetic peripheral neuropathy.
Topics: Humans; Diabetic Neuropathies; Duloxetine Hydrochloride; Capsaicin; Gabapentin; Pregabalin; Pain; Diabetes Mellitus
PubMed: 38574212
DOI: No ID Found -
The Primary Care Companion For CNS... Jan 2024
Topics: Humans; Duloxetine Hydrochloride; Hallucinations
PubMed: 38277643
DOI: 10.4088/PCC.23cr03595 -
International Journal of Molecular... Feb 2022While cardiovascular disease (CVD) is the leading cause of death, major depressive disorder (MDD) is the primary cause of disability, affecting more than 300 million...
While cardiovascular disease (CVD) is the leading cause of death, major depressive disorder (MDD) is the primary cause of disability, affecting more than 300 million people worldwide. Interestingly, there is evidence that CVD is more prevalent in people with MDD. It is well established that neurotransmitters, namely serotonin and norepinephrine, are involved in the biochemical mechanisms of MDD, and consequently, drugs targeting serotonin-norepinephrine reuptake, such as duloxetine, are commonly prescribed for MDD. In this connection, serotonin and norepinephrine are also known to play critical roles in primary hemostasis. Based on these considerations, we investigated if duloxetine can be repurposed as an antiplatelet medication. Our results-using human and/or mouse platelets show that duloxetine dose-dependently inhibited agonist-induced platelet aggregation, compared to the vehicle control. Furthermore, it also blocked agonist-induced dense and α-granule secretion, integrin αIIbβ3 activation, phosphatidylserine expression, and clot retraction. Moreover duloxetine-treated mice had a significantly prolonged occlusion time. Finally, duloxetine was also found to impair hemostasis. Collectively, our data indicate that the antidepressant duloxetine, which is a serotonin-norepinephrine antagonist, exerts antiplatelet and thromboprotective effects and inhibits hemostasis. Consequently, duloxetine, or a rationally designed derivative, presents potential benefits in the context of CVD, including that associated with MDD.
Topics: Animals; Antidepressive Agents; Depressive Disorder, Major; Duloxetine Hydrochloride; Hemostasis; Humans; Mice; Norepinephrine; Platelet Activation; Platelet Aggregation; Platelet Glycoprotein GPIIb-IIIa Complex; Serotonin; Serotonin Antagonists; Thrombosis
PubMed: 35269729
DOI: 10.3390/ijms23052587 -
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 -
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 -
Advances in Rheumatology (London,... Jul 2020Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more... (Review)
Review
BACKGROUND
Duloxetine and amitriptyline are antidepressants used in the treatment of fibromyalgia. In published systematic reviews, there is no agreement about which drug is more effective and safer. This study aimed to compare evidence of the efficacy and safety of duloxetine compared with amitriptyline in the treatment of adult patients with fibromyalgia. This work contributes to guiding clinicians on the use of duloxetine or amitriptyline for the treatment of fibromyalgia and provides information for public health decision-makers.
METHODS
Overview of systematic reviews of clinical trials comparing duloxetine and amitriptyline in the treatment of fibromyalgia. The reviews were screened in Cochrane, PubMed, EMBASE, and SRDR with no restrictions on language and year of publication, considering that the research was conducted in July 2018 and updated until May 2020. The selection was based on the following criteria: adult patients with a diagnosis of fibromyalgia treated with duloxetine or amitriptyline, comparing the efficacy and safety in pain, fatigue, sleep, and mood disorder symptoms and quality of life, in addition to the acceptability of these antidepressants. The methodological quality and strength of evidence were assessed using the AMSTAR and GRADE instruments.
RESULTS
Eight systematic reviews were selected. Amitriptyline had low evidence for pain, moderate evidence for sleep and fatigue, and high evidence for quality of life. Duloxetine had high quality of evidence in patients with mood disorders. With low evidence, duloxetine has higher acceptability, but is safer in older patients, while amitriptyline is safer for non-elderly individuals.
CONCLUSION
Both antidepressants are effective in the treatment of fibromyalgia, differing according to the patient's symptoms and profile.
REGISTRATION
PROSPERO: CRD42019116101.
Topics: Amitriptyline; Antidepressive Agents; Duloxetine Hydrochloride; Fibromyalgia; Humans; Syndrome; Systematic Reviews as Topic
PubMed: 32641165
DOI: 10.1186/s42358-020-00137-5 -
The Journal of Neuroscience : the... Jan 2022Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN). While it...
Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN). While it is only effective in little more than half of patients, our ability to predict patient response remains incompletely understood. Given that stress exacerbates CIPN, and that the therapeutic effect of duloxetine is thought to be mediated, at least in part, via its effects on adrenergic mechanisms, we evaluated the contribution of neuroendocrine stress axes, sympathoadrenal and hypothalamic-pituitary-adrenal, to the effect of duloxetine in preclinical models of oxaliplatin- and paclitaxel-induced CIPN. Systemic administration of duloxetine, which alone had no effect on nociceptive threshold, both prevented and reversed mechanical hyperalgesia associated with oxaliplatin- and paclitaxel-CIPN. It more robustly attenuated oxaliplatin CIPN in male rats, while it was more effective for paclitaxel CIPN in females. Gonadectomy attenuated these sex differences in the effect of duloxetine. To assess the role of neuroendocrine stress axes in the effect of duloxetine on CIPN, rats of both sexes were submitted to adrenalectomy combined with fixed level replacement of corticosterone and epinephrine. While CIPN, in these rats, was of similar magnitude to that observed in adrenal-intact animals, rats of neither sex responded to duloxetine. Furthermore, duloxetine blunted an increase in corticosterone induced by oxaliplatin, and prevented the exacerbation of CIPN by sound stress. Our results demonstrate a role of neuroendocrine stress axes in duloxetine analgesia (anti-hyperalgesia) for the treatment of CIPN. Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating dose-dependent and therapy-limiting side effect of many of the cytostatic drugs used to treat cancer (Argyriou et al., 2010; Marmiroli et al., 2017). Duloxetine is the only treatment for CIPN currently recommended by the American Society of Clinical Oncology (Hershman et al., 2014). In the present study, focused on elucidating mechanisms mediating the response of oxaliplatin- and paclitaxel-induced painful peripheral neuropathy to duloxetine, we demonstrate a major contribution to its effect of neuroendocrine stress axis function. These findings, which parallel the clinical observation that stress may impact response of CIPN to duloxetine (Taylor et al., 2007), open new approaches to the treatment of CIPN and other stress-associated pain syndromes.
Topics: Analgesics; Animals; Antineoplastic Agents; Corticosterone; Duloxetine Hydrochloride; Female; Male; Oxaliplatin; Paclitaxel; Pain Management; Pain Threshold; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley
PubMed: 34880120
DOI: 10.1523/JNEUROSCI.1691-21.2021 -
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