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Pain Practice : the Official Journal of... Jan 2015With anticonvulsant, anxiolytic, and analgesic properties, pregabalin has been evaluated for neuropathic pain and fibromyalgia (FM). These chronic conditions diminish... (Review)
Review
BACKGROUND
With anticonvulsant, anxiolytic, and analgesic properties, pregabalin has been evaluated for neuropathic pain and fibromyalgia (FM). These chronic conditions diminish patients' quality of life and increase healthcare utilization and costs.
OBJECTIVE
To assess the current understanding of economic outcomes associated with pregabalin in neuropathic pain and FM.
METHODS
Using keywords related to economic outcomes and pregabalin, we systematically searched MEDLINE- and EMBASE-indexed literature and nonindexed "grey" literature on neuropathic pain and FM published from March 2001 to October 2012. Included studies reported economic findings associated with pregabalin.
RESULTS
In the past 11 years, 55 publications assessed the direct costs, resource use, or cost-effectiveness of pregabalin for neuropathic pain and FM. Studies generally lacked comparability due to heterogeneous patient populations, assumptions, time periods, and geographies. In the US, following treatment initiation, pregabalin resulted in similar or higher levels of healthcare use for FM compared with duloxetine. In contrast, medical costs for neuropathic pain did not significantly differ after initiation of pregabalin vs. duloxetine or other standard therapies in the US, but in Spain and Sweden, retrospective database studies suggested that pregabalin was cost-saving vs. gabapentin. Few economic analyses estimated indirect costs.
CONCLUSIONS
Neuropathic pain and FM are associated with high healthcare resource use and costs. Economic studies of pregabalin in neuropathic pain and FM indicate some results favorable to other forms of care, but heterogeneity among study designs and populations hinder comparisons. Future economic analyses should aim to address data gaps regarding effects of pregabalin on productivity and resource use.
Topics: Amines; Analgesics; Anticonvulsants; Chronic Disease; Cost-Benefit Analysis; Cyclohexanecarboxylic Acids; Duloxetine Hydrochloride; Economics, Pharmaceutical; Fibromyalgia; Gabapentin; Health Services; Humans; Neuralgia; Pregabalin; Quality of Life; Quality-Adjusted Life Years; Spain; Sweden; United States; gamma-Aminobutyric Acid
PubMed: 24815038
DOI: 10.1111/papr.12193 -
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 -
Journal of Affective Disorders May 2023Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses.... (Randomized Controlled Trial)
Randomized Controlled Trial
A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.
BACKGROUND
Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD).
METHODS
In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD) total score. Secondary endpoints and safety were evaluated.
RESULTS
Least-squares mean change in HAM-D total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%).
LIMITATIONS
A short-term non-inferiority study without a placebo arm.
CONCLUSIONS
This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.
Topics: Adult; Humans; Duloxetine Hydrochloride; Depressive Disorder, Major; Desvenlafaxine Succinate; Antidepressive Agents; Double-Blind Method; Treatment Outcome
PubMed: 36813043
DOI: 10.1016/j.jad.2023.02.067 -
Current Urology Reports Jul 2024Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress... (Review)
Review
PURPOSE OF REVIEW
Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress made in surgical techniques, pharmacotherapy has not yielded substantial outcomes within the clinical domain. This review aims to present a comprehensive overview of the existing pharmacotherapy options for stress urinary incontinence (SUI) and the emerging therapeutic targets in this field.
RECENT FINDINGS
One meta-analysis demonstrated that α-adrenergic medications are more efficacious in improving rather than curing SUI symptoms. One trial showed reduced pad weight gain with PSD-503, a locally administered α-adrenergic receptor agonist. New data show that duloxetine's risk outweighs its benefits. One small-scale trial was found to support the use of locally administered estriol in improving subjective outcomes. Emerging targets include serotonin 5HT agonists, selective inhibitors of norepinephrine uptake, and myostatin inhibitors. Only one of the evaluated drugs, duloxetine, has been approved by some countries. Currently, trials are evaluating novel targets. Systemic adverse effects such as gastrointestinal upset with duloxetine and orthostatic hypotension with α-adrenoceptor agonists have hampered the efficacy of drugs used to treat SUI in women and men.
Topics: Humans; Urinary Incontinence, Stress; Duloxetine Hydrochloride; Female; Male
PubMed: 38727982
DOI: 10.1007/s11934-024-01205-9 -
Acta Psychiatrica Scandinavica Jun 2018Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and venlafaxine, and at analysing a potential influence of the investigated drugs on the placebo response.
METHOD
We conducted a comprehensive systematic review and meta-analysis of placebo-controlled, double-blind RCTs, which examined the efficacy of duloxetine and venlafaxine in the acute treatment of major depressive disorder.
RESULTS
We included 71 studies (29 duloxetine trials and 43 venlafaxine trials; one study provided data for the duloxetine and the venlafaxine data set). The placebo effect sizes, defined as pre-postscore change divided by baseline standard deviation, differed significantly between venlafaxine and duloxetine studies (-2.51 vs. -2.09; test for subgroup differences P = 0.028; high heterogeneity). The analysis of effect modifiers and the metaregression analyses confirmed the drug, next to baseline depression severity and publication status, as the most influential independent predictor.
CONCLUSION
Our analyses show a significant difference in the placebo response between venlafaxine and duloxetine trials and suggest that the investigated drug has an influence on the placebo response that is not related to baseline severity, changes over the years or other variables we included.
Topics: Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Placebo Effect; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 29603140
DOI: 10.1111/acps.12881 -
BMC Musculoskeletal Disorders Feb 2022Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result of experienced non-nociceptive centralized pain. Placebo-controlled randomized trials (RCT) have proven the effectiveness of duloxetine for OA and several chronic pain conditions where central sensitization (CS) is one of the key underlying pain mechanisms.
OBJECTIVES
Assess the efficacy of an 8-week duloxetine treatment compared to usual care in end-stage knee and hip OA patients with a level of centralized pain.
DESIGN
Pragmatic, enriched, open-label RCT.
METHODS
Patients were randomized to duloxetine or to care-as-usual. Primary outcome was pain in the index joint, measured with the pain domain of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS). The intention-to-treat principle was used, with mixed-model repeated measures to analyze the effect.
RESULTS
One hundred eleven patients were randomized. Nearly 44% felt much to very much better after duloxetine usage compared to 0% in the care-as-usual group (p < 0.001). The duloxetine group scored 11.3 points (95%CI: 5.8, 16.8) better on the pain domain of the KOOS/HOOS (p < 0.001). Knee patients improved significantly more than hip patients (18.7 [95%CI: 11.3, 26.1] versus 6.0 [95%CI: - 2.6, 14.5] points better).
CONCLUSIONS
Adding duloxetine treatment seems to be beneficial for end-stage knee OA patients with neuropathic-like symptoms (at risk of CS). End stage Hip OA patients seem to be nonresponsive to duloxetine.
TRIAL REGISTRATION
Dutch Trial Registry with number NTR 4744 (15/08/2014) and in the EudraCT database with number 2013-004313-41 .
Topics: Chronic Pain; Duloxetine Hydrochloride; Humans; Osteoarthritis, Hip; Osteoarthritis, Knee; Treatment Outcome
PubMed: 35123461
DOI: 10.1186/s12891-022-05034-0 -
BMC Pulmonary Medicine Aug 2023Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Refractory cough, a chronic cough with an unclear diagnosis or poor treatment response. The symptoms are often stubborn and persistent, causing serious complications and lowering the patient's quality of life. Cough hypersensitivity syndrome (CHS) is proposed as a potential cause, and reducing sensory nerve hyperresponsiveness is suggested as an effective treatment. However, current drugs have low efficacy and benefit rates and numerous side effects. This trail proposes using duloxetine, a selective 5-HT and norepinephrine reuptake inhibitor, as a potential treatment for refractory cough, which has shown promise in treating pain and depression. Duloxetine may inhibit pain conduction and oxidative stress in peripheral nerves by inhibiting the activity of TRPV1 channels, which play an important role in the peripheral afferent pathway of refractory cough. Meanwhile, the antidepressant effects of duloxetine may also play a role in the treatment of refractory cough.
METHODS AND ANALYSIS
This is a single-center, prospective, randomized, double-blind, and controlled trial. A total of 98 individuals will be randomized in a 1:1 ratio to duloxetine group and placebo control group (starting with 20 mg QD, increasing 20 mg daily until 20 mg TID). After a screening period, the second stage runs from baseline to the 42nd (last) day of treatment, with follow-up visits on the 3rd, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days. The main end-stage observation indicators include objective cough frequency, cough visual analog scale (VAS), cough symptom score, Leicester Cough Questionnaire (LCQ), and cough evaluation test (CET); the secondary end-stage observation indicators include capsaicin cough sensitivity, Patient Health Questionnaire-9 (PHQ-9), Major Depression Inventory (MDI), the Generalized Anxiety Disorder-7 scale (GAD-7), Life Events Scale (LES-32), induced sputum supernatant. The safety measures will be AEs/SAEs, vital signs, liver and kidney function, fecal occult blood test.
DISCUSSION
This study is the first randomized, double-blind, and controlled clinical trial investigating the use of duloxetine in the treatment of refractory coughs. The study aims to provide a high-quality basis for evaluating the efficacy and safety of duloxetine for this condition.
TRIAL REGISTRATION
Our study was registered in the Chinese Clinical Trials Register ( www.chictr.org.cn/ ) (ChiCTR2000037429) in 28/08/2020.
Topics: Humans; Duloxetine Hydrochloride; Cough; Tablets, Enteric-Coated; Quality of Life; Prospective Studies; Pain; Double-Blind Method; Treatment Outcome
PubMed: 37533019
DOI: 10.1186/s12890-023-02575-5 -
Systematic Reviews Apr 2022Duloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use compared to non-elderly is not clearly...
Tolerability of duloxetine in elderly and in non-elderly adults: a protocol of a systematic review and individual participant data meta-analysis of randomized placebo-controlled trials.
BACKGROUND
Duloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use compared to non-elderly is not clearly assessed. This protocol outlines a systematic review and individual participant data meta-analysis comparing the tolerability of duloxetine between elderly and non-elderly.
METHODS
Searches will be conducted in PubMed, ClinicalTrials.gov , Clinicaltrialsregister.eu, data sharing platforms, FDA drug approval packages, European public assessment reports and withdrawn applications from the EMA website. The review will be performed on studies available in electronic databases from their date of inception to the 31 March 2022. Only randomized controlled clinical trials, comparing duloxetine to placebo, will be included in this meta-analysis. The studies will be selected if they comprise both elderly and non-elderly adults, in conditions of use of duloxetine approved by the European Medical Agency (EMA) and the Food and Drug Administration (FDA). The primary outcome will be the rate ratio of serious adverse events under duloxetine compared to placebo, between participants at least 65 years old and non-elderly. Second, the number of any adverse events, clinical efficacy and quality of life will be compared between elderly and non-elderly under both interventions. The quality of evidence in the tolerability of duloxetine will be assessed using the GRADE system. A one or two-stage individual participant data random effect meta-analysis will be conducted depending on the availability of the data.
DISCUSSION
This meta-analysis will investigate the tolerability safety of duloxetine in the elderly population across all conditions approved by European and American regulatory authorities. The results from this meta-analysis are intended to help prescribers to provide better care for the elderly population.
SYSTEMATIC REVIEW REGISTRATION
The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42019130488 ).
Topics: Adult; Aged; Antidepressive Agents; Duloxetine Hydrochloride; Humans; Meta-Analysis as Topic; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Treatment Outcome
PubMed: 35428340
DOI: 10.1186/s13643-022-01945-0