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Biomedicine & Pharmacotherapy =... Dec 2023Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be...
BACKGROUND
Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be elucidated whether these associations are related to exposure to antidepressants, a consequence of a disease process, or a combination of both.
METHODS
This study investigates the independent effect of the antidepressant duloxetine hydrochloride (DH) on ovariectomy-induced bone loss in mice. One week after ovariectomy, the treated mice received DH. To explore the mechanism underlying the rescue of bone loss, bone marrow cells were isolated from mouse femurs and tibias, and macrophages extracted from them were induced to become osteoclasts in vitro while being treated with DH. Subsequently, the osteoclasts underwent Bulk RNA-Seq to reveal the involved signaling pathways. The results of the bioinformatic analysis were then validated through in vitro experiments.
RESULTS
The in vivo experiments demonstrated that DH treatment compromised ovariectomy-induced bone loss after 7 weeks. The in vitro experiments suggested that DH treatment attenuated osteoclast differentiation via the MAPKs/NFATc1 signaling pathway.
CONCLUSION
The findings from this study suggest that DH, instead of causing bone mass loss, may assist in alleviating postmenopausal osteoporosis. These results can serve as a reference for the clinical treatment of patients with perimenopausal or postmenopausal depression using antidepressants.
Topics: Humans; Female; Animals; Mice; Osteoclasts; Duloxetine Hydrochloride; Depressive Disorder, Major; Cell Differentiation; Antidepressive Agents; Ovariectomy; Osteogenesis; RANK Ligand
PubMed: 37913736
DOI: 10.1016/j.biopha.2023.115810 -
International Journal of Molecular... May 2023Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only...
Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED, von Frey testing) and thermal hyperalgesia (ED, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED and ED for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.
Topics: Mice; Animals; Paclitaxel; Duloxetine Hydrochloride; Rosuvastatin Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pain Measurement; Neuralgia; Hyperalgesia; Analgesics
PubMed: 37176065
DOI: 10.3390/ijms24098359 -
Anticancer Research Oct 2022Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may... (Review)
Review
Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a chemotherapy dose reduction and a cessation of administration of chemotherapeutic drugs. Its principal sensory symptoms include, tingling, and numbness in the hands and feet. Severe pain can be encompassed among clinical manifestations. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory symptoms may occur for months, or even years after the termination of chemotherapeutic drugs. Although many pharmacological and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized treatment for CIPN. According to current guidelines, Duloxetine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective therapies for CIPN is mandatory. The aim of this review was to dissect CIPN, the target and immunotherapy-based approaches to this disorder, as well as to offer new insights for new therapeutic perspectives.
Topics: Antineoplastic Agents; Duloxetine Hydrochloride; Humans; Pain; Peripheral Nervous System Diseases; Quality of Life
PubMed: 36191965
DOI: 10.21873/anticanres.15971 -
Bioanalysis Nov 2021To develop an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite, 4-hydroxy duloxetine glucuronide (4HDG) in human plasma and to...
To develop an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite, 4-hydroxy duloxetine glucuronide (4HDG) in human plasma and to investigate the potential back-conversion of 4HDG to duloxetine using stability study. The LC-MS/MS method was validated according to the EMA and USFDA Bioanalytical Method Validation Guidelines and applied to pilot bioequivalence study. The method validation results were within the acceptance limits. The stability study and incurred sample reanalysis results ruled out the occurrence of back-conversion. The study highlighted the conduct of back-conversion test and the advantages of LC-MS/MS method in terms of sensitivity, specificity and low consumption of organic solvents.
Topics: Adolescent; Adult; Area Under Curve; Chromatography, High Pressure Liquid; Duloxetine Hydrochloride; Glucuronides; Half-Life; Humans; Quality Control; ROC Curve; Tandem Mass Spectrometry; Therapeutic Equivalency; Young Adult
PubMed: 34743613
DOI: 10.4155/bio-2021-0185 -
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 -
Molecular Pain 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting...
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting oncology patients' quality of life, chemotherapy-induced large-fiber (LF) neuropathy is amongst the least well understood components of CIPN, and one for which there is currently no established therapy. Preliminary clinical observations have led to the suggestion that Duloxetine, which is used for the treatment of pain associated with small-fiber CIPN (SF-CIPN), may be effective against LF-CIPN. In the present experiments we developed a model of LF-CIPN and studied the effect of Duloxetine on LF-CIPN induced by two neurotoxic chemotherapy agents: the proteasome inhibitor, Bortezomib, a first-line treatment of multiple myeloma; and, the anti-microtubule taxane, Paclitaxel, used in the treatment of solid tumors. Since there are currently no models for selective the study of LF-CIPN, our first aim was to establish a pre-clinical model in the rat. LF-CIPN was evaluated with the Current Perception Threshold (CPT) assay, which uses a high frequency (1000 Hz) electrical stimulus protocol that selectively activates large-fiber myelinated afferents. Our second aim was to use this model to test the hypothesis that Duloxetine can prevent LF-CIPN. We report that Bortezomib and Paclitaxel induce elevation of CPT, compatible with loss of large-fiber function, which are prevented by Duloxetine. Our findings support the clinical observation that Duloxetine may be an effective treatment for the large-fiber CIPN. We also suggest that CPT could be used as a biomarker for LF-CIPN in patients receiving neurotoxic chemotherapy.
Topics: Rats; Animals; Paclitaxel; Duloxetine Hydrochloride; Bortezomib; Rats, Sprague-Dawley; Quality of Life; Peripheral Nervous System Diseases; Antineoplastic Agents
PubMed: 37338165
DOI: 10.1177/17448069231185694 -
Journal of Child and Adolescent... Jun 2023Childhood mental illness is an ongoing public health crisis which is accompanied by an increase in antidepressant (i.e., serotonin reuptake inhibitors and... (Review)
Review
Childhood mental illness is an ongoing public health crisis which is accompanied by an increase in antidepressant (i.e., serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) use in children. Recent evidence highlighting the cultural differences in the utilization, efficacy, and tolerability of antidepressants in children underscores the need for diverse samples in studies examining antidepressant use. Furthermore, the American Psychological Association in recent years has emphasized the importance of including participants from diverse backgrounds in research studies, including investigations of medication efficacy. The present study, therefore, examined the demographic composition of samples used and reported in antidepressant efficacy and tolerability studies with children and adolescents experiencing anxiety and/or depression in the last decade. A systematic literature review utilizing two databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In line with the extant literature, antidepressants were operationalized as , , , , and Out of the 11 articles included in this review, 71% reported having a primarily adolescent sample (i.e., over 50% of the sample was 12 years or older). In addition, studies omitted any transgender, genderqueer, or gender-nonconforming demographics, and one study omitted all racial demographic information. While 64% of studies only partially reported racial demographic information, 36% of studies omitted ethnicity demographics altogether. The present study addresses a gap in the literature by supporting a lack of diversity in studies examining antidepressant use in children and adolescents. Furthermore, it underscores the importance of future studies using a more diverse and representative sample. Limitations of the present study included limited generalizability and the lack of independent and blind reviewer process. Possible explanations for the lack of inclusion and suggestions on how to address these disparities are discussed.
Topics: Child; Adolescent; Humans; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Fluoxetine; Sertraline; Duloxetine Hydrochloride
PubMed: 37253162
DOI: 10.1089/cap.2022.0090 -
Archives of Gynecology and Obstetrics Sep 2023Stress urinary incontinence (SUI) is defined as urinary incontinence that occurs with coughing, sneezing, and physical exercise. It is frequently observed in women after...
OBJECTIVES
Stress urinary incontinence (SUI) is defined as urinary incontinence that occurs with coughing, sneezing, and physical exercise. It is frequently observed in women after middle age and has a negative impact on their sexual function. Duloxetine as one of the Serotonin-noradrenaline reuptake inhibitors (SNRIs) is commonly used in the non-surgical treatment of SUI. The aim of our study is to investigate the effect of duloxetine, which is used in the treatment of SUI, on sexual functions in female patients.
METHODS
The study included 40 sexually active patients who received duloxetine 40 mg twice a day for the treatment of SUI. All patients had female sexual function index (FSFI), Beck's depression inventory (BDI), and incontinence quality of life score (I-QOL) applied before and 2 months after starting duloxetine treatment.
RESULTS
FSFI total score significantly increased from 19.9 to 25.7 (p < 0.001). In addition, significant improvement was observed in all sub-parameters of FSFI, including arousal, lubrication, orgasm, satisfaction, and pain/discomfort (p < 0.001, for each FSFI subtotal score). BDI significantly decreased from 4.5 to 1.5 (p < 0.001). I-QOL score significantly increased from 57.6 to 92.7 after the duloxetine treatment.
CONCLUSIONS
Although SNRIs carry a high risk of sexual dysfunction, duloxetine may have an indirect positive effect on female sexual activity, both through its stress incontinence treatment and its antidepressant effect. In our study, Duloxetine, one of the treatment options for stress urinary incontinence and an SNRI, has a positive effect on stress urinary incontinence, mental health, and sexual activity in patients with SUI.
Topics: Female; Humans; Middle Aged; Duloxetine Hydrochloride; Norepinephrine; Quality of Life; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Urinary Incontinence, Stress; Sexual Dysfunction, Physiological
PubMed: 37386151
DOI: 10.1007/s00404-023-07123-4 -
Acta Crystallographica. Section E,... Apr 2023Duloxetine hydro-chloride (trade name Cymbalta) is marketed as a single enanti-omer ()--methyl-3-(naphthalen-1-yl-oxy)-3-(thio-phen-2-yl)propyl-am-in-ium chloride,...
Duloxetine hydro-chloride (trade name Cymbalta) is marketed as a single enanti-omer ()--methyl-3-(naphthalen-1-yl-oxy)-3-(thio-phen-2-yl)propyl-am-in-ium chloride, CHNOS·Cl, which is twice as effective as the ()-enanti-omer in serotonin uptake. Here, we report the crystal structure of duloxetine hydro-chloride in its racemic form (space group 2), where it shows significant differences in the mol-ecular conformation and packing in its extended structure compared to the previously reported ()-enanti-omer crystal structure. Mol-ecules of this type, comprising aromatic groups with a single side chain terminated in a protonated secondary amine, are commonly found in active anti-depressants. A Cambridge Structural Database survey of mol-ecules with these features reveals a strong correlation between side-chain conformation and the crystal packing: an extended side chain leads to mol-ecules packed into separated layers of hydro-phobic and ionic hydro-philic phases. By comparison, mol-ecules with bent side chains, such as racemic duloxetine hydro-chloride, lead to crystal-packing motifs where an ionic hydro-philic phase is encapsulated within a hydro-phobic shell.
PubMed: 37151834
DOI: 10.1107/S2056989023003353 -
Diabetes Research and Clinical Practice Dec 2023Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant...
Painful Diabetic Peripheral Neuropathy (PDN) is common, affecting around a quarter of patients with both type 1 and type 2 diabetes, and can lead to significant curtailment of functionality and quality of life. Patients may present with unremitting burning, aching or "electric-shock" type pains in their feet, legs and later, in the hands. Conventional management approaches must focus not only on pain relief, but also on concurrent sleep problems, mood disorders and functionality. The mainstay of treatment is pharmacotherapy. Most current international guidelines recommend a choice of four drugs: amitriptyline, duloxetine, pregabalin or gabapentin, as initial treatment for PDN. Recent evidence from the OPTION-DM trial demonstrated that these drugs and their combinations have equivalent efficacy. Moreover, combination treatment provided significant pain relief to patients with inadequate response to the maximum tolerated dose of monotherapy. PDN refractory to pharmacotherapy can be treated with capsaicin 8% or high frequency spinal cord stimulation.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Quality of Life; Duloxetine Hydrochloride; Pain
PubMed: 38245323
DOI: 10.1016/j.diabres.2023.110765