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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 -
Biomedicine & Pharmacotherapy =... Jun 2019It is known that users of psychotropic drugs often have weight gain, adverse effects on bone mineral density and osteoporosis, but the molecular basis for these side...
It is known that users of psychotropic drugs often have weight gain, adverse effects on bone mineral density and osteoporosis, but the molecular basis for these side effects is poorly understood. The aim of this study is to evaluate the effects in vitro of duloxetine (a serotonin and norepinephrine reuptake inhibitor) and fluoxetine (a selective serotonin reuptake inhibitor) on the physiology of human adult stem cells. Adipose-derived stem cells (ADSCs) were isolated and characterized investigating phenotype morphology, expression and frequency of surface markers. Then, a non-toxic concentration of duloxetine and fluoxetine was selected to treat cells during adipogenic and osteogenic differentiation. Stemness properties and the differentiation potential of drug-treated cells were investigated by the quantification of adipogenic and osteogenic markers gene expression and histological staining. The collected data showed that the administration of a daily non-toxic dose of duloxetine and fluoxetine has not directly influenced ADSCs proliferation and their stemness properties. The treatment with duloxetine or fluoxetine did not lead to morphological alterations during adipogenic or osteogenic commitment. However, treatments with the antidepressant showed a slight difference in adipogenic gene expression timing. Furthermore, duloxetine treatment caused an advance in gene expression of early and late osteogenic markers. Fluoxetine instead caused an increase in expression of osteogenic genes compared to untreated cells. In contrast, in pre-differentiated cells, the daily treatment with duloxetine or fluoxetine did not alter the expression profile of adipogenic and osteogenic differentiation. In conclusion, a non-toxic concentration of duloxetine and fluoxetine does not alter the stemness properties of ADSCs and does not prevent the commitment of pre-differentiated ADSCs in adipocytes or osteocyte. Probably, the weight gain and osteoporotic effects associated with the use of psychotropic drugs could be closely related to the direct action of serotonin.
Topics: Adipocytes; Adipogenesis; Adipose Tissue; Adult; Antidepressive Agents; Cell Differentiation; Cell Proliferation; Cells, Cultured; Duloxetine Hydrochloride; Fluoxetine; Gene Expression; Humans; Mesenchymal Stem Cells; Osteocytes; Osteogenesis; Osteoporosis; Selective Serotonin Reuptake Inhibitors; Young Adult
PubMed: 30986624
DOI: 10.1016/j.biopha.2019.108853 -
BMJ (Clinical Research Ed.) Feb 2020To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine.
OBJECTIVE
To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine.
DESIGN
Cohort study nested in the Medicaid Analytic eXtract for 2004-13.
SETTING
Publicly insured pregnancies in the United States.
PARTICIPANTS
Pregnant women 18 to 55 years of age and their liveborn infants.
INTERVENTIONS
Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy.
MAIN OUTCOME MEASURES
Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage.
RESULTS
Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses.
CONCLUSIONS
On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient.
TRIAL REGISTRATION
EUPAS 15946.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Cohort Studies; Duloxetine Hydrochloride; Female; Heart Defects, Congenital; Humans; Infant, Small for Gestational Age; Middle Aged; Postpartum Hemorrhage; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Premature Birth; Prenatal Exposure Delayed Effects; Serotonin and Noradrenaline Reuptake Inhibitors; United States; Young Adult
PubMed: 32075794
DOI: 10.1136/bmj.m237 -
Drug Discoveries & Therapeutics Nov 2022The purpose of this study is to compare the efficacy and safety of pharmacotherapies for chronic pain due to osteoarthritis (OA) between a group with duloxetine (DLX)...
Comparison of efficacy and safety in the combination therapies of duloxetine and S-flurbiprofen plaster, and of duloxetine and conventional NSAIDs for chronic pain in patients with osteoarthritis (OASIS DUAL study).
The purpose of this study is to compare the efficacy and safety of pharmacotherapies for chronic pain due to osteoarthritis (OA) between a group with duloxetine (DLX) and S-flurbiprofen plaster (SFPP) (the SFPP group) and a group with DLX and conventional non-steroidal anti-inflammatory drugs (NSAIDs) (the control group). The subjects were 49 patients (17 men and 32 women). The evaluation of factors associated with treatment termination due to symptoms improvement showed that significantly more women terminated treatment than did men, and significantly more members of the SFPP group terminated treatment than did members of the control group. The visual analogue scale (VAS) score in the SFPP group was significantly improved from 6.6 ± 1.7 before treatment to 3.6 ± 2.1 one month later and showed significant difference until nine months later. The VAS score in the control group was significantly improved from 6.7 ± 1.9 to 4.1 ± 2.8 one month later. The VAS score improvement rate was significantly higher in the SFPP group than in the control group, suggesting that the DLX-SFPP combination had higher efficacy than the DLX-conventional NSAIDs combination. The incidence of adverse drug reactions was 55% in the SFPP group, which is not significantly different from 50% incidence in the control group. The treatment discontinuation rate due to adverse drug reactions, however, was 60% in the control group and 19% in the SFPP group. It was suggested that the efficacy and safety of the DLX-SFPP combination for chronic pain due to OA are equal to or higher than that of the DLX-conventional NSAIDs combination.
Topics: Humans; Male; Female; Flurbiprofen; Duloxetine Hydrochloride; Chronic Pain; Anti-Inflammatory Agents, Non-Steroidal; Osteoarthritis; Drug-Related Side Effects and Adverse Reactions; Treatment Outcome
PubMed: 36223938
DOI: 10.5582/ddt.2022.01052 -
Clinical Cancer Research : An Official... Nov 2019Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity, negatively affecting both quality of life and disease outcomes. To date, there... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting toxicity, negatively affecting both quality of life and disease outcomes. To date, there is no proven preventative strategy for CIPN. Although multiple randomized trials have evaluated a variety of pharmacologic interventions for the treatment of CIPN, only duloxetine has shown clear efficacy in a phase III study. The National Cancer Institute's Symptom Management and Health-Related Quality of Life Steering Committee has identified CIPN as a priority for translational research in cancer care. Promising advances in preclinical research have identified several novel preventative and therapeutic targets, which have the potential to transform the care of patients with this debilitating neurotoxicity. Here, we provide an overarching view of emerging strategies and therapeutic targets that are currently being evaluated in CIPN.
Topics: Antineoplastic Agents; Clinical Trials, Phase III as Topic; Drug-Related Side Effects and Adverse Reactions; Duloxetine Hydrochloride; Humans; Peripheral Nervous System Diseases; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 31123053
DOI: 10.1158/1078-0432.CCR-18-2152 -
Contemporary Clinical Trials Jun 2024Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can...
BACKGROUND
Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination.
METHODS
This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires.
CONCLUSION
The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www.
CLINICALTRIALS
gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.
Topics: Adult; Female; Humans; Male; Middle Aged; Antidepressive Agents; Anxiety; Combined Modality Therapy; Depression; Duloxetine Hydrochloride; Patient Education as Topic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38604496
DOI: 10.1016/j.cct.2024.107524 -
The Clinical Journal of Pain May 2023Duloxetine is a serotonin-norepinephrine reuptake inhibitor prescribed for musculoskeletal and other forms of chronic pain. Its dual pharmacologic properties have the...
OBJECTIVE
Duloxetine is a serotonin-norepinephrine reuptake inhibitor prescribed for musculoskeletal and other forms of chronic pain. Its dual pharmacologic properties have the potential to either raise or lower cardiovascular risk: adrenergic activity may increase the risk for acute myocardial infarction (AMI) and stroke, but antiplatelet activity may decrease risk. Gabapentin is another nonopioid medication used to treat pain, which is not thought to have adrenergic/antiplatelet effects. With the current emphasis on the use of nonopioid medications to treat patients with chronic pain, assessing cardiovascular risks associated with these medications among high-risk patients is important.
MATERIALS AND METHODS
We conducted a retrospective cohort study among a 20% sample of Medicare enrollees, aged 65 to 89, with chronic pain who were new users between 2015 and 2018 of either duloxetine (n = 34,009) or gabapentin (n = 233,060). We excluded individuals with cancer or other life-threatening conditions at study drug initiation. The primary outcome was a composite of AMI, stroke, and out-of-hospital mortality. We adjusted for comorbidity differences with time-dependent inverse probability of treatment weighting.
RESULTS
During 115,668 person-years of follow-up, 2361 patients had the composite primary outcome; the rate among new users of duloxetine was 16.7/1000 person-years compared with new users of gabapentin (21.1/1000 person-years), adjusted hazard ratio = 0.98 (95% CI: 0.83, 1.16). Results were similar for the individual components of the composite outcome as well as in analyses stratified by demographic and clinical characteristics.
DISCUSSION
In summary, cohort Medicare patients with non-cancer pain beginning treatment with duloxetine had rates of AMI, stroke, and out-of-hospital mortality comparable to those who initiated gabapentin.
Topics: Humans; Aged; United States; Duloxetine Hydrochloride; Gabapentin; Medicare; Retrospective Studies; Chronic Pain; Stroke; Myocardial Infarction; Hospitals
PubMed: 37094085
DOI: 10.1097/AJP.0000000000001105 -
PloS One 2021The purpose of this study was to assess the efficacy of duloxetine as an alternative to opioid treatment for postoperative pain management following total knee... (Comparative Study)
Comparative Study
BACKGROUND
The purpose of this study was to assess the efficacy of duloxetine as an alternative to opioid treatment for postoperative pain management following total knee arthroplasty (TKA).
METHODS
Among 944 patients, 290 (30.7%) of patients received opioid or duloxetine for pain control for 6 weeks when the pain Visual Analogue Scale (VAS) score was greater than 4 out of 10 at the time of discharge. 121 patients in the Opioid group and 118 in the Duloxetine group were followed up for more than one year. Preoperative and postoperative patient reported outcome measures (pain VAS score, Western Ontario and McMaster Universities OA Index (WOMAC) score were compared. The rate of further drug prescription (opioid or duloxetine) after 6 weeks of first prescription, 30-day readmission rate, and side effects were also investigated.
RESULTS
There was no significant difference in pain VAS score, WOMAC Pain and Function score, at each time point between before and after surgery (all p>0.05). Fifteen (9.8%) patients in the opioid group and six (4.4%) patients in the duloxetine group were prescribed additional medication after first 6 weeks, showing no significant (p>0.05) difference in proportion. The 30-day readmission rate and the incidence of side effects were also similar (all p>0.05). There was no difference in the incidence of side effects between the two groups (p>0.05).
CONCLUSION
Duloxetine and opioid did not show any difference in pain control, function, and side effects for up to one year after TKA. Although large-scale randomized controlled trials are still required to further confirm the side effects of duloxetine, it can be considered as an alternative to opioid for postoperative pain control following TKA.
Topics: Aged; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Duloxetine Hydrochloride; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ontario; Osteoarthritis, Knee; Pain Management; Pain Measurement; Pain, Postoperative; Patient Readmission; Patient Reported Outcome Measures; Retrospective Studies; Treatment Outcome
PubMed: 34214098
DOI: 10.1371/journal.pone.0253641 -
International Journal of Molecular... Dec 2017Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and...
Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α₁-adrenergic receptor antagonists, 10 μg); however, idazoxan (α₂-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α₁-adrenergic receptors.
Topics: Adrenergic alpha-2 Receptor Antagonists; Animals; Duloxetine Hydrochloride; Male; Mice; Mice, Inbred C57BL; Neuralgia; Neurons; Organoplatinum Compounds; Oxaliplatin; Rats; Rats, Sprague-Dawley; Spinal Cord
PubMed: 29206213
DOI: 10.3390/ijms18122626 -
BMC Musculoskeletal Disorders May 2021Previous studies have demonstrated the efficacy of duloxetine in reducing postoperative pain and opioid consumption. However, the effect of duloxetine on total hip... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have demonstrated the efficacy of duloxetine in reducing postoperative pain and opioid consumption. However, the effect of duloxetine on total hip arthroplasty (THA) remains unclear. The objective of this study was to assess the efficacy of oral duloxetine in THA.
METHODS
We enrolled 96 patients in this randomized controlled trial. These patients were randomized (1,1) to either the duloxetine group or the placebo group and received daily doses of 60 mg duloxetine or placebo, respectively, from 2 d pre-operation to 14 d after surgery. The primary outcome was pain severity upon movement measured by a visual analogue scale (VAS). The secondary outcomes included VAS scores for resting pain, morphine consumption, Harris Hip Score, patient satisfaction at discharge, length of postoperative hospital stay, and adverse events.
RESULTS
Patients in the duloxetine group had significantly lower pain severity scores upon movement within 3 postoperative weeks (p < 0.05) while none of the differences met the minimum clinically important difference (MCID). Moreover, patients in the duloxetine group performed better in terms of resting pain (in 3 weeks after surgery), morphine requirements, and satisfaction level at discharge (all p < 0.05). There was no difference between groups in the prevalence of adverse events.
CONCLUSIONS
Although it did not result in a clinically meaning reduction in pain after total hip arthroplasty, perioperative administration of 60 mg of duloxetine daily significantly alleviated pain in the postoperative 3 weeks and morphine requirements during the postoperative 48 h. Therefore, duloxetine still shows promise in optimizing the multimodal pain-management protocols in total hip arthroplasty.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2000033606 , 06/06/2020.
Topics: Analgesics; Arthroplasty, Replacement, Hip; Double-Blind Method; Duloxetine Hydrochloride; Humans; Prospective Studies
PubMed: 34049519
DOI: 10.1186/s12891-021-04377-4