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Osteoarthritis and Cartilage Jan 2021Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States.
OBJECTIVE
Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States.
DESIGN
We used a validated computer simulation of knee OA to compare usual care (UC) - intra-articular injections, opioids, and total knee replacement (TKR) - to UC preceded by duloxetine in those no longer achieving pain relief from non-steroidal anti-inflammatory drugs (NSAIDs). Outcomes included quality-adjusted life years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). We considered cohorts with mean ages 57-75 years and Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain 25-55 (0-100, 100-worst). We derived inputs from published data. We discounted costs and benefits 3% annually. We conducted sensitivity analyses of duloxetine efficacy, duration of pain relief, toxicity, and costs.
RESULTS
Among younger subjects with severe pain (WOMAC pain = 55), duloxetine led to an additional 9.6 QALYs per 1,000 subjects (ICER = $88,500/QALY). The likelihood of duloxetine being cost-effective at willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY was 40% and 54%. Offering duloxetine to older patients with severe pain led to ICERs >$150,000/QALY. Offering duloxetine to subjects with moderate pain (pain = 25) led to ICERs <$50,000/QALY, regardless of age. Among knee OA subjects with severe pain (pain = 55) who are unwilling or unable to undergo TKR, ICERs were <$50,600/QALY, regardless of age.
CONCLUSIONS
Duloxetine is a cost-effective addition to knee OA UC for subjects with moderate pain or those with severe pain unable or unwilling to undergo TKR. Among younger subjects with severe pain, duloxetine is cost-effective at WTP thresholds >$88,500/QALY.
Topics: Aged; Analgesics; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Computer Simulation; Cost-Benefit Analysis; Duloxetine Hydrochloride; Glucocorticoids; Humans; Injections, Intra-Articular; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Quality-Adjusted Life Years
PubMed: 33171315
DOI: 10.1016/j.joca.2020.10.001 -
Brain and Behavior Mar 2020Neuropathic pain occurs in 1% of the population and is difficult to manage. This chronic pain causes psychological distress and impacts patient's quality of life,... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Neuropathic pain occurs in 1% of the population and is difficult to manage. This chronic pain causes psychological distress and impacts patient's quality of life, especially in cancer patients. The aim of this study was to show and compare the efficacy of pregabalin and duloxetine, which are reported in the group of first-line treatment at European Federation of Neurological Societies (EFNS) guidelines on the pharmacological treatment of neuropathic pain (2010 revision) in lung cancer patients by using visual analogue scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Sign (LANSS).
PATIENTS AND METHODS
A prospective, randomized, open label, 3 month of study was conducted. A total of 44 patients that were diagnosed with neuropathic pain (14 women and 30 men) were included in the study. Patient's LANSS and VAS values were recorded before treatment. Then, 22 patients undergo pregabalin and 22 patients undergo duloxetine therapy. But due to side effects (dizziness, constipation), two patients had stopped to use pregabalin. Their LANSS and VAS values were recorded after 1 and 3 months of therapy.
RESULTS
When we compare LANSS and VAS scores before treatment, after 1 and 3 months of treatment with pregabalin and duloxetine, a significant decrease was observed in both groups at the 1 and 3 months (p < .01). Duloxetine is superior to pregabalin in reducing the LANSS scores when we compare two groups.
CONCLUSIONS
Both duloxetine and pregabalin are effective in the treatment of neuropathic pain of lung cancer patients. And as far as we know, this is the first study comparing the efficacy of duloxetine and pregabalin in the neuropathic pain of lung cancer patients.
Topics: Adult; Aged; Aged, 80 and over; Analgesics; Cancer Pain; Duloxetine Hydrochloride; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neuralgia; Pain Measurement; Pregabalin; Prospective Studies; Quality of Life; Treatment Outcome
PubMed: 31967742
DOI: 10.1002/brb3.1527 -
Journal of Neuroscience Research Jun 2017Central noradrenergic centers such as the locus coeruleus (LC) are traditionally viewed as pain inhibitory; however, complex interactions among brainstem pathways and... (Review)
Review
Central noradrenergic centers such as the locus coeruleus (LC) are traditionally viewed as pain inhibitory; however, complex interactions among brainstem pathways and their receptors modulate both inhibition and facilitation of pain. In addition to the well-described role of descending pontospinal pathways that inhibit spinal nociceptive transmission, an emerging body of research now indicates that noradrenergic neurons in the LC and their terminals in the dorsal reticular nucleus (DRt), medial prefrontal cortex (mPFC), spinal dorsal horn, and spinal trigeminal nucleus caudalis participate in the development and maintenance of allodynia and hyperalgesia after nerve injury. With time after injury, we argue that the balance of LC function shifts from pain inhibition to pain facilitation. Thus, the pain-inhibitory actions of antidepressant drugs achieved with elevated noradrenaline concentrations in the dorsal horn may be countered or even superseded by simultaneous activation of supraspinal facilitating systems dependent on α -adrenoreceptors in the DRt and mPFC as well as α -adrenoreceptors in the LC. Indeed, these opposing actions may account in part for the limited treatment efficacy of tricyclic antidepressants and noradrenaline reuptake inhibitors such as duloxetine for the treatment of chronic pain. We propose that the traditional view of the LC as a pain-inhibitory structure be modified to account for its capacity as a pain facilitator. Future studies are needed to determine the neurobiology of ascending and descending pathways and the pharmacology of receptors underlying LC-mediated pain inhibition and facilitation. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Antidepressive Agents, Tricyclic; Chronic Pain; Duloxetine Hydrochloride; Humans; Locus Coeruleus; Norepinephrine; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 27685982
DOI: 10.1002/jnr.23956 -
The Clinical Journal of Pain Nov 2021We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain.
METHODS
A comprehensive literature search used 3 English and 4 Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of 2 weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and adverse events (AEs). The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072).
RESULTS
Six studies totaling 2059 patients met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24 hours average pain (mean difference [MD]=-0.74; 95% confidence interval [CI], -0.92 to -0.57; P<0.00001; I2=13%; 5 trials; 1695 patients); patient general activity (MD=-0.76; 95% CI, -0.96 to -0.56; P<0.00001; I2=0%; 5 trials; 1694 patients) WOMAC physical function subscale (MD=-4.22; 95% CI, -5.14 to -3.30; P<0.00001; I2=26%; 5 trials; 1986 patients); Patient's Global Impression of Improvement (MD=-0.48; 95% CI, -0.58 to -0.37; P<0.00001; I2=29%; 5 trials; 1741 patients); and Clinical Global Impressions of Severity (MD=-0.34; 95% CI, -0.44 to -0.24; P<0.00001; I2=0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (standard mean difference=-1.68; 95% CI, -3.45 to 0.08; P=0.06; I2=100%; 3 trials; 1104 patients) and in serious AEs (risk ratio=0.92; 95% CI, 0.40-2.11; P=0.84; I2=0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent AEs.
CONCLUSION
Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.
Topics: Duloxetine Hydrochloride; Humans; Knee Joint; Osteoarthritis, Knee; Pain; Pain Measurement
PubMed: 34483232
DOI: 10.1097/AJP.0000000000000975 -
Cleveland Clinic Journal of Medicine Jul 2005
Topics: Benzilates; Duloxetine Hydrochloride; Humans; Nortropanes; Parasympatholytics; Primary Health Care; Selective Serotonin Reuptake Inhibitors; Thiophenes; Urinary Incontinence; Urinary Incontinence, Stress
PubMed: 16044651
DOI: 10.3949/ccjm.72.7.544 -
Annals of Palliative Medicine Mar 2021A comprehensive approach to pain management often requires multimodal therapy and a combination of medications. Oncology patients may be prescribed methadone and...
BACKGROUND
A comprehensive approach to pain management often requires multimodal therapy and a combination of medications. Oncology patients may be prescribed methadone and duloxetine as single agents or in combination for cancer-related pain, particularly neuropathic pain. Duloxetine is also prescribed for depression or anxiety in patients with cancer.
METHODS
A retrospective chart review on patients with cancer-related pain prescribed duloxetine and methadone combination therapy at the Virginia Commonwealth University supportive care clinic (SCC) between 2012 and 2019. Edmonton Symptom Assessment System (ESAS) scores reported by patients on monotherapy were compared to scores after they started combination therapy. Of 131 patients identified on combination therapy, 43 met study criteria (2 with incomplete ESAS scores).
RESULTS
ESAS total and subscores after combination therapy were lower than on monotherapy. Combination therapy decreased total, pain, and emotion subscores by 5.6 (SD =17.3, dz =-0.32, P=0.046), 0.9 (SD =3.0, dz =-0.30, P=0.052), and 1.8 (SD =5.1, dz =-0.36, P=0.023), respectively. On combination therapy, 28% of patients reported at least a two-point reduction in pain scores. All study participants reported cancer pain with neuropathic components; most had mixed pain syndromes comprising nociceptive and neuropathic components. Adherence rates were high as 81% of patients with follow-up appointments continued therapy.
CONCLUSIONS
These results suggest the combination of duloxetine and methadone reduces cancer-related pain and emotional symptom burden compared to either medication as a single agent.
Topics: Cancer Pain; Duloxetine Hydrochloride; Humans; Methadone; Neoplasms; Retrospective Studies; Treatment Outcome
PubMed: 33474965
DOI: 10.21037/apm-20-1455 -
Medicine Nov 2019Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous clinical trials indicated that duloxetine may be effective in the treatment of osteoarthritis (OA) pain. This meta-analysis is conducted to evaluate short term analgesic effect and safety of duloxetine in the treatment of OA.
METHODS
Electronic databases were searched in February 2019, including PUBMED, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Web of Science. All eligible studies should be randomized controlled trials (RCTs) comparing duloxetine treatment group to placebo about OA pain relief and safety outcomes.
RESULTS
Five RCTs with 2059 patients were involved in this systematic review and meta-analysis. Compared to placebo, duloxetine treatment showed significant better result, with higher reduction pain intensity (mean difference [MD] = -0.77, P < .00001), higher rates of both 30% and 50% reduction in pain severity (risk ratio [RR] = 1.42, P < .00001; RR = 1.62, P < .00001), lower mean Patient Global Improvement-Inventory (PGI-I) score (MD = -0.48, P < .00001). The results of the Western Ontario and McMaster Universities (WOMAC) score change from baseline to endpoint also favored duloxetine treatment group in all four categories, including total (MD = -5.43, P < .00001), pain (MD = -1.63, P = .001), physical function (MD = -4.22, P < .00001), and stiffness score (MD = -0.58, P < .00001). There were higher rates of treatment-emergent adverse events (TEAEs) (RR = 1.32, P < .00001) and discontinuation (RR = 1.88, P < .00001) in duloxetine group. However, there was no significant difference in the incidence of severe adverse events (SAEs) between these 2 groups (RR = 0.84, P = .68).
CONCLUSION
Duloxetine was an effective and safe choice to improve pain and functional outcome in OA patients. However, further studies are still needed to find out the optimal dosage for OA and examine its long-term efficacy and safety.
TRIAL REGISTRATION NUMBER
CRD42019128862.
Topics: Analgesics; Duloxetine Hydrochloride; Humans; Ontario; Osteoarthritis; Pain Measurement; Patient Acuity; Physical Functional Performance; Randomized Controlled Trials as Topic
PubMed: 31689755
DOI: 10.1097/MD.0000000000017541 -
Drug Metabolism and Disposition: the... Feb 2022Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor, widely used for the treatment of major depressive disorder. Although DLX has shown good...
Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor, widely used for the treatment of major depressive disorder. Although DLX has shown good efficacy and safety, serious adverse effects (e.g., liver injury) have been reported. The mechanisms associated with DLX-induced toxicity remain elusive. Drug metabolism plays critical roles in drug safety and efficacy. However, the metabolic profile of DLX in mice is not available, although mice serve as commonly used animal models for mechanistic studies of drug-induced adverse effects. Our study revealed 39 DLX metabolites in human/mouse liver microsomes and mice. Of note, 13 metabolites are novel, including five -acetyl cysteine adducts and one reduced glutathione (GSH) adduct associated with DLX. Additionally, the species differences of certain metabolites were observed between human and mouse liver microsomes. CYP1A2 and CYP2D6 are primary enzymes responsible for the formation of DLX metabolites in liver microsomes, including DLX-GSH adducts. In summary, a total of 39 DLX metabolites were identified, and species differences were noticed in vitro. The roles of CYP450s in DLX metabolite formation were also verified using human recombinant cytochrome P450 (P450) enzymes and corresponding chemical inhibitors. Further studies are warranted to address the exact role of DLX metabolism in its adverse effects in vitro (e.g., human primary hepatocytes) and in vivo (e.g., Cyp1a2-null mice). SIGNIFICANCE STATEMENT: This current study systematically investigated Duloxetine (DLX) metabolism and bioactivation in liver microsomes and mice. This study provided a global view of DLX metabolism and bioactivation in liver microsomes and mice, which are very valuable to further elucidate the mechanistic study of DLX-related adverse effects and drug-drug interaction from metabolic aspects.
Topics: Animals; Depressive Disorder, Major; Duloxetine Hydrochloride; Mice; Microsomes, Liver; Serotonin; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 34785568
DOI: 10.1124/dmd.121.000633 -
BMC Musculoskeletal Disorders Mar 2014This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis.
METHODS
A systematic literature review of English language articles was performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and opioids were included if treatment was ≥12 weeks and the Western Ontario and McMaster Universities Index (WOMAC) total score was available. Studies were assessed for quality using the assessment tool from the National Institute for Health and Clinical Excellence guidelines for single technology appraisal submissions.WOMAC baseline and change from baseline total scores were extracted and standardized. A frequentist meta-analysis, meta-regression, and indirect comparison were performed using the DerSimonian-Laird and Bucher methods. Bayesian analyses with and without adjustment for study-level covariates were performed using noninformative priors.
RESULTS
Thirty-two publications reported 34 trials (2 publications each reported 2 trials) that met inclusion criteria. The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo. Indirect comparisons to duloxetine found no significant differences for most of the compounds. Some analyses showed evidence of a difference with duloxetine for etoricoxib (better), tramadol and oxycodone (worse), but without consistent results between analyses. Forest plots revealed positive trends in overall efficacy improvement with baseline scores. Adjusting for baseline, the probability duloxetine is superior to other treatments ranges between 15% to 100%.Limitations of this study include the low number of studies included in the analyses, the inclusion of only English language publications, and possible ecological fallacy associated with patient level characteristics.
CONCLUSIONS
This analysis suggests no difference between duloxetine and other post-first line oral treatments for osteoarthritis (OA) in total WOMAC score after approximately 12 weeks of treatment. Significant results for 3 compounds (1 better and 2 worse) were not consistent across performed analyses.
Topics: Acetaminophen; Administration, Oral; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Drug Evaluation; Duloxetine Hydrochloride; Etoricoxib; Humans; Narcotics; Osteoarthritis; Pain Measurement; Pyridines; Sulfones; Thiophenes; Treatment Outcome
PubMed: 24618328
DOI: 10.1186/1471-2474-15-76 -
BMC Neurology Nov 2010Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic... (Review)
Review
BACKGROUND
Patients frequently fail to receive adequate pain relief from, or are intolerant of, first-line therapies prescribed for neuropathic pain (NeP). This refractory chronic pain causes psychological distress and impacts patient quality of life. Published literature for treatment in refractory patients is sparse and often published as conference abstracts only. The aim of this study was to identify published data for three pharmacological treatments: pregabalin, lidocaine plaster, and duloxetine, which are typically used at 2(nd) line or later in UK patients with neuropathic pain.
METHODS
A systematic review of the literature databases MEDLINE, EMBASE and CCTR was carried out and supplemented with extensive conference and grey literature searching. Studies of any design (except single patient case studies) that enrolled adult patients with refractory NeP were included in the review and qualitatively assessed.
RESULTS
Seventeen studies were included in the review: nine of pregabalin, seven of the lidocaine plaster, and one of duloxetine. No head-to-head studies of these treatments were identified. Only six studies included treatments within UK licensed indications and dose ranges. Reported efficacy outcomes were not consistent between studies. Pain scores were most commonly assessed in studies including pregabalin; trials of pregabalin and the lidocaine plaster reported the proportion of responders. Significant improvements in the total, sensory and affective scores of the Short-form McGill Pain Questionnaire, and in function interference, sleep interference and pain associated distress, were associated with pregabalin treatment; limited or no quality of life data were available for the other two interventions. Limitations to the review are the small number of included studies, which are generally small, of poor quality and heterogeneous in patient population and study design.
CONCLUSIONS
Little evidence is available relevant to the treatment of refractory neuropathic pain despite the clinical need. There is a notable lack of high-quality comparative studies. It is evident that there is a need for future, high quality trials, particularly "gold-standard" RCTs in this refractory patient population.
Topics: Analgesics; Anesthetics, Local; Duloxetine Hydrochloride; Humans; Lidocaine; Neuralgia; Pregabalin; Thiophenes; Treatment Outcome; gamma-Aminobutyric Acid
PubMed: 21092100
DOI: 10.1186/1471-2377-10-116