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Trials May 2024Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and...
Duloxetine and cognitive behavioral therapy with phone-based support for the treatment of chronic musculoskeletal pain: study protocol of the PRECICE randomized control trial.
BACKGROUND
Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT.
METHODS
Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of three treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI, and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment.
DISCUSSION
This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills, thereby enhancing treatment outcomes.
TRIAL REGISTRATION
NCT04395001 ClinicalTrials.gov. Registered on May 15, 2020.
Topics: Duloxetine Hydrochloride; Humans; Cognitive Behavioral Therapy; Chronic Pain; Musculoskeletal Pain; Randomized Controlled Trials as Topic; Treatment Outcome; Combined Modality Therapy; Pain Measurement; Telephone; Motivational Interviewing; Analgesics; Time Factors; Internet-Based Intervention; Pain Management; Adaptation, Psychological; Adult
PubMed: 38762720
DOI: 10.1186/s13063-024-08158-x -
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 -
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 -
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 -
Pain Research & Management 2022There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary...
There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was "on demand" (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.
Topics: Acetaminophen; Amitriptyline; Analgesics; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Dipyrone; Duloxetine Hydrochloride; Fibromyalgia; Humans; Neuralgia; Pregabalin; Selective Serotonin Reuptake Inhibitors
PubMed: 36247103
DOI: 10.1155/2022/1217717 -
CNS Drug Reviews 2002Dysregulation within central monoaminergic systems is believed to underlie the pathology of depression. Drugs that selectively inhibit the reuptake of central monoamines... (Review)
Review
Dysregulation within central monoaminergic systems is believed to underlie the pathology of depression. Drugs that selectively inhibit the reuptake of central monoamines have been used clinically to alleviate symptoms of depressive illnesses. Duloxetine, a novel compound currently under investigation for the treatment of depression, binds selectively with high affinity to both norepinephrine (NE) and serotonin (5-HT) transporters and lacks affinity for monoamine receptors within the central nervous system. It has been suggested that dual inhibition of monoamine reuptake processes may offer advantages over other antidepressants currently in use. In preclinical studies, duloxetine mimics many physiologic effects of antidepressants. Consistent with other antidepressants, duloxetine, by acute administration, elevates extracellular monoamine levels, while by chronic administration it does not alter basal monoamine levels. Like the selective serotonin reuptake inhibitor, fluoxetine, by microiontophoretic application, duloxetine inhibits neuronal cell firing. However, in comparison with fluoxetine, duloxetine is a more potent serotonin reuptake inhibitor. Furthermore, in behavioral experiments, duloxetine attenuates immobility in forced swim tests in animal models of depression to a greater extent than several other commonly used antidepressants. In a six-week open label uncontrolled study, duloxetine was evaluated in patients with a history of depression. Duloxetine was effective in treating depression as determined by marked reduction in Hamilton Depression Rating scores. Adverse effects reported during duloxetine treatment were minor and similar to those of other antidepressants. In an eight-week multicenter, double-blind, placebo-controlled study in patients with a major depressive disorder, duloxetine was effective as an antidepressant, particularly in patients with greater symptom severity. Only limited data are available regarding the pharmacokinetic profile of duloxetine in humans, although a half-life of 10 to 15 h has been reported. Studies conducted in healthy human subjects confirm the preclinical profile of duloxetine as an inhibitor of 5-HT and NE reuptake. Taken together, existing data suggest that duloxetine is a novel and effective antidepressant.
Topics: Adrenergic Uptake Inhibitors; Animals; Antidepressive Agents; Behavior, Animal; Biogenic Monoamines; Brain; Clinical Trials as Topic; Depressive Disorder; Duloxetine Hydrochloride; Electrophysiology; Humans; Selective Serotonin Reuptake Inhibitors; Thiophenes; Treatment Outcome
PubMed: 12481192
DOI: 10.1111/j.1527-3458.2002.tb00234.x -
Contrast Media & Molecular Imaging 2022Diabetic peripheral neuropathic pain (DPNP) is a common chronic pain condition affecting diabetic patients and has growing importance because of the increasing... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetic peripheral neuropathic pain (DPNP) is a common chronic pain condition affecting diabetic patients and has growing importance because of the increasing prevalence of patients with type 2 diabetes mellitus. Pain is the most troublesome symptom of DPNP, increasingly recognized as an important and independent feature of DPNP. This meta-analysis aims to compare the efficacy and safety of duloxetine and gabapentin in the treatment of diabetic peripheral neuropathic pain (DPNP) and therefore to provide evidence-based medicine for clinical treatment.
METHODS
Relevant randomized controlled trials on duloxetine versus gabapentin for DPNP were searched from PubMed, Embase, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and Chinese Biomedical Literature Database from database inception to October 2021. The data were analyzed by RevMan 5.3 software.
RESULTS
Seven studies were included. The results showed that, at the end of the study, duloxetine was significantly superior to gabapentin in terms of the incidence of adverse reactions (RR = 0.59, 95% CI: 0.45-0.79, < 0.01), sleep interference score (SMD = -0.35, 95% CI: -0.63 to -0.08, < 0.05), but no significant differences in VAS score (SMD = -0.14, 95% CI: -0.31-0.03, > 0.05), overall response rate (RR = 1.05, 95% CI: 0.92-1.20, > 0.05), and clinical global impression of change (SMD = 0.07, 95% CI: -0.20-0.35, > 0.05).
CONCLUSION
Compared with gabapentin, duloxetine has no obvious advantage in the treatment of diabetic peripheral neuralgia, but it has less side effects and significantly higher safety.
Topics: Analgesics; Chronic Disease; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Duloxetine Hydrochloride; Gabapentin; Humans; Neuralgia
PubMed: 35299589
DOI: 10.1155/2022/4084420 -
International Journal of Molecular... Aug 2023Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence...
Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.
Topics: Humans; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Cytochrome P-450 CYP1A2; Duloxetine Hydrochloride; Depression; Drug-Related Side Effects and Adverse Reactions; Polymorphism, Genetic
PubMed: 37686266
DOI: 10.3390/ijms241713459 -
Diabetes Care Sep 2013Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical... (Review)
Review
Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. α-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment.
Topics: Diabetic Neuropathies; Duloxetine Hydrochloride; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin; Thiophenes; gamma-Aminobutyric Acid
PubMed: 23970715
DOI: 10.2337/dc12-1964 -
Arquivos de Gastroenterologia 2019Gastric cancer is the second leading cause of cancer-related death globally. Unfortunately, the survival rate of the gastric cancer patients who underwent chemotherapy...
BACKGROUND
Gastric cancer is the second leading cause of cancer-related death globally. Unfortunately, the survival rate of the gastric cancer patients who underwent chemotherapy following surgery has been less than a half. Besides, chemotherapy has many side effects. Current evidence suggests that some antidepressants like duloxetine have growth-inhibiting effects against a number of cancer cell lines.
OBJECTIVE
Thus, the aim of this study was to determine the cytotoxic and genotoxic effects of duloxetine on gastric cancer.
METHODS
In this regard, the cytotoxicity and genotoxicity of duloxetine were investigated in MKN45 and NIH3T3 cell lines by MTT assay and on peripheral blood lymphocytes by MN assay. For this purpose, cells were cultured in 96 wells plate. Stock solutions of duloxetine and cisplatin were prepared. After cell incubation with different concentrations of duloxetine (1, 10, 25, 50, 100 and 200 μL), MTT solution was added. For micronucleus assay fresh blood was added to RPMI culture medium 1640 supplemented, and different concentrations of duloxetine (1, 10, 25, 50, 100 and 200 μL) were added.
RESULTS
The cytotoxicity of duloxetine on MKN45 cancer cell line and NIH3T3 normal cell line were studied followed by MTT assay. duloxetine exhibited higher IC50 in the MKN45 cells in comparison with the NIH3T3 cells. In addition, genotoxic effect of duloxetine was evaluated by micronucleus assay. The results revealed that duloxetine induced more DNA damage at 100 and 200 μM and no significant difference at 200 μM with respect to cisplatin, but it had less genotoxic effects at 100 and 50 μM concentrations.
CONCLUSION
Although, in this study, duloxetine had less genotoxicity than cisplatin in concentrations under 200 μM and showed cytotoxic effects as well, due to its IC50, it cannot be considered as a better choice for gastric cancer therapies with respect to cisplatin as a common anticancer drug.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; DNA Damage; Dose-Response Relationship, Drug; Duloxetine Hydrochloride; Humans; Lymphocytes; Mice; Mutagenicity Tests; NIH 3T3 Cells; Stomach Neoplasms
PubMed: 31721971
DOI: 10.1590/S0004-2803.201900000-71