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Duloxetine hydrochloride，a serotonin-norepinephrine reuptake inhibitor （SNRIs）， is a commonly used antidepressants. Its mechanism of action involves increasing synaptic monoamine neurotransmitters concentration， leading to antidepressant effects. While gastrointestinal reactions and elevated blood pressure are common side effects， duloxetine can rarely induce syndrome of inappropriate antidiuretic hormone secretion （SIADH）. This case report presents a patient with depression who developed SIADH following duloxetine hydrochloride initiation， with the main clinical manifestation being restless thirst and excessive drinking. This case is presented to raise awareness among clinicians of this rare yet potentially serious adverse effect of duloxetine treatment.

Background: Conditioned pain modulation (CPM) is a potential predictor of treatment response that has not been studied in temporomandibular disorders (TMD). Objectives: We conducted a randomised, double‐blind, placebo‐controlled trial (RCT) of duloxetine in addition to self‐management (SM) strategies to investigate its efficacy to reduce pain intensity in painful TMD patients. Moreover, we investigated whether baseline CPM would predict the duloxetine efficacy to reduce TMD pain intensity. Methods: Eighty participants were randomised to duloxetine 60 mg or placebo for 12 weeks. The primary outcomes were the change in the pain intensity from baseline to week‐12 and CPM‐sequential paradigm at baseline. Safety, physical and emotional functioning outcomes were also evaluated. Results: Of 80 participants randomised, 78 were included in intention‐to‐treat analysis. Pain intensity decreased for SM‐duloxetine and SM‐placebo but did not differ between groups (p =.82). A more efficient CPM was associated with a greater pain intensity reduction regardless of the treatment group (p =.035). Physical and emotional functioning did not differ between groups, but adverse events (p =.014), sleep impairment (p =.003) and catastrophizing symptoms (p =.001) were more prevalent in SM‐duloxetine group. Conclusion: This study failed to provide evidence of a beneficial effect of adding duloxetine to SM strategies for treatment of painful TMD. Nonetheless, this RCT has shown the feasibility of applying pain modulation assessment to predict short‐term treatment response in painful TMD patients, which confirms previous finds that CPM evaluation may serve a step forward in individualising pain treatment. [ABSTRACT FROM AUTHOR]

Abstract Aim To identify the phenotypic characteristics of individuals with temporomandibular disorders (TMD) who may benefit from adding duloxetine to self-management (SM) strategies. Methodology This was a post hoc exploratory analysis of a randomized, placebo-controlled clinical trial with SM-duloxetine (duloxetine 60 mg/day plus SM strategies for 12 weeks) in adult participants with painful TMD. The primary outcome was the proportion of responders to treatment (individuals with ≥ 30% reduction in pain intensity) in SM-duloxetine and SM-placebo group at week 12. For responder analysis, five phenotyping domains recommended by Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials were assessed: pain, psychological, sleep, quantitative sensory testing, and conditioned pain modulation. Relative risk (RR), 95% confidence intervals (CI), and absolute risk reduction were calculated. Results Among participants treated with SM-duloxetine, severe pain intensity (RR 1.33, 95% CI: 0.56, 3.17), pain disability (RR 1.30, 95% CI: 0.63, 2.67), ≥ 1 painful comorbidity (RR 1.48, 95% CI: 0.57, 3.79), and anxiety symptoms (RR 1.80, 95% CI: 0.75, 4.34) were associated with greater likelihood of response to treatment. Among individuals treated with SM-placebo, only temporal summation of pain was associated with greater likelihood of response to treatment. Conclusion Personalized medicine may be implemented in painful TMD management, and phenotype characteristics related to pain and psychological domains may predict which individuals with painful TMD are more likely to respond to the addition of serotonin and norepinephrine reuptake inhibitors to SM strategies to clinically and significantly reduce pain intensity.

Duloxetine hydrochloride, a serotonin-norepinephrine reuptake inhibitor (SNRIs), is a commonly used antidepressants. Its mechanism of action involves increasing synaptic monoamine neurotransmitters concentration, leading to antidepressant effects. While gastrointestinal reactions and elevated blood pressure are common side effects, duloxetine can rarely induce syndrome of inappropriate antidiuretic hormone secretion (SIADH). This case report presents a patient with depression who developed SIADH following duloxetine hydrochloride initiation, with the main clinical manifestation being restless thirst and excessive drinking. This case is presented to raise awareness among clinicians of this rare yet potentially serious adverse effect of duloxetine treatment. [ABSTRACT FROM AUTHOR]

Background & Objective: Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by changes in bowel movements and abdominal pain in the absence of structural disorders. Although effective treatment for irritable bowel syndrome is not yet available. One of the treatments is the low-dose antidepressants, depending on the type and severity of the disease. This study was performed to compare the effect of selective serotonin-norepinephrine reuptake inhibitors including duloxetine and imipramine from a tricyclic antidepressant Materials & Methods: forty-eight definitively diagnosed IBS patients (based on Rome III criteria) were examined in 2 groups of men and women. Patients in the control group were treated with Dicyclomine and Imipramine while the case group received dicyclomine and duloxetine. The outcomes were measured before and 3 months after treatment to determine and compare the improvement in responses (mainly diarrhea). Results: Duloxetine could significantly improve the symptoms such as abdominal pain in females (P-value: 0.01) and males (P-value: 0.001), bloating in females (Pvalue: 0.004) and incomplete defecation in females (P-value: 0.001) and in males (Pvalue: 0.007). The side effects of this drug were, however, higher than Imipramine. The introduction of more appropriate treatment requires further studies on a larger sample size to assess the symptoms and the side effects. Conclusion: Based on the effect of duloxetine on this clinical results, it is recommended as an effective treatment in controlling of abdominal pain, bloating, and incomplete defecation. [ABSTRACT FROM AUTHOR]

Asthma is an inflammatory disease characterized by airway hyperresponsiveness, airway remodeling, and airway inflammation. In recent years, the prevalence of asthma has been increasing steadily and the pathogenesis of asthma varies from person to person. Due to poor compliance or resistance, existing drugs cannot achieve the desired therapeutic effect. Therefore, developing or screening asthma therapeutic drugs with high curative effects, low toxicity, and strong specificity is very urgent. Duloxetine HCl (DUX) is a selective serotonin and norepinephrine reuptake inhibitor, and it was mainly used to treat depression, osteoarthritis, and neuropathic pain. It was also reported that DUX has potential anti-infection, anti-inflammation, analgesic, antioxidative, and other pharmacological effects. However, whether DUX has some effects on asthma remains unknown. In order to investigate it, a series of ex vivo and in vivo experiments, including biological tension tests, patch clamp, histopathological analysis, lung function detection, oxidative stress enzyme activity detection, and molecular biology experiments, were designed in this study. We found that DUX can not only relax high potassium or ACh precontracted tracheal smooth muscle by regulating L-type voltage-dependent Ca2+ channel (L-VDCC) and nonselective cation channel (NSCC) ion channels but also alleviate asthma symptoms through anti-inflammatory and antioxidative response regulated by PI3K/AKT/mTOR and Nrf2/HO-1 signaling pathways. Our data suggests that DUX is expected to become a potential new drug for relieving or treating asthma. [ABSTRACT FROM AUTHOR]

Background: Neuropathy is a common complication in diabetic patients with clinical manifestations of feet and hands paresthesia, pain in the lower legs, and a burning sensation in the soles. A wide variety of medications are used for diabetic neuropathy with varying degrees of pain relief reported. The study objective was to compare the efficacy of duloxetine versus pregabalin for pain relief of neuropathy in diabetics. Methods: The study was a six-week, single-blind, Randomized Controlled Trial conducted at HBS Medical and Dental College and Hospital in Islamabad. Patients were randomly designated to either of the groups (A or B) with 50 participants in each group. Group A received 150mg of pregabalin twice a day while group B received 60mg of duloxetine once a day. Pain relief was the primary outcome which was considered as a ≥ 50% decrease in pain score on the Visual Analog Scale at 6 weeks from baseline. Results: A total of 100 diabetic patients were registered in the study. The mean age in groups A&B was 48.36 and 50.56 SD± 6.64) years respectively. The majority of the study population were males 39 (78%) and 42 (84%) in both groups. A total of 66% (n=33) in Group A and 74% (n=37) of the patients in Group B achieved pain relief. A comparison of the pain relief achieved between the two groups showed no statistical significance (p-value 0.383). Conclusion: The study revealed that duloxetine and pregabalin are both efficacious in terms of pain relief for diabetic neuropathy in our population.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is the best-established treatment for painful chemotherapy-induced peripheral neuropathy (CIPN). While it is only effective in little more than half of patients, our ability to predict patient response remains incompletely understood. Given that stress exacerbates CIPN, and that the therapeutic effect of duloxetine is thought to be mediated, at least in part, via its effects on adrenergic mechanisms, we evaluated the contribution of neuroendocrine stress axes, sympathoadrenal and hypothalamic-pituitary-adrenal, to the effect of duloxetine in preclinical models of oxaliplatin- and paclitaxel-induced CIPN. Systemic administration of duloxetine, which alone had no effect on nociceptive threshold, both prevented and reversed mechanical hyperalgesia associated with oxaliplatin- and paclitaxel-CIPN. It more robustly attenuated oxaliplatin CIPN in male rats, while it was more effective for paclitaxel CIPN in females. Gonadectomy attenuated these sex differences in the effect of duloxetine. To assess the role of neuroendocrine stress axes in the effect of duloxetine on CIPN, rats of both sexes were submitted to adrenalectomy combined with fixed level replacement of corticosterone and epinephrine. While CIPN, in these rats, was of similar magnitude to that observed in adrenal-intact animals, rats of neither sex responded to duloxetine. Furthermore, duloxetine blunted an increase in corticosterone induced by oxaliplatin, and prevented the exacerbation of CIPN by sound stress. Our results demonstrate a role of neuroendocrine stress axes in duloxetine analgesia (anti-hyperalgesia) for the treatment of CIPN.SIGNIFICANCE STATEMENT Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating dose-dependent and therapy-limiting side effect of many of the cytostatic drugs used to treat cancer (Argyriou et al., 2010; Marmiroli et al., 2017). Duloxetine is the only treatment for CIPN currently recommended by the American Society of Clinical Oncology (Hershman et al., 2014). In the present study, focused on elucidating mechanisms mediating the response of oxaliplatin- and paclitaxel-induced painful peripheral neuropathy to duloxetine, we demonstrate a major contribution to its effect of neuroendocrine stress axis function. These findings, which parallel the clinical observation that stress may impact response of CIPN to duloxetine (Taylor et al., 2007), open new approaches to the treatment of CIPN and other stress-associated pain syndromes.

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.

Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL suffers limited bioavailability due to extensive gastric and first-pass metabolism. To improve DUL's bioavailability; DUL-loaded elastosomes were developed, via full factorial design, utilizing various span®60: cholesterol ratios, edge activator types and amounts. Entrapment efficiency (E.E.%), particle size (PS), zeta potential (ZP) and in-vitro released percentages after 0.5 h (Q0.5h) and 8 h (Q8h) were evaluated. Optimum elastosomes (DUL-E1) were assessed for morphology, deformability index, drug crystallinity and stability. DUL pharmacokinetics were evaluated in rats following intranasal and transdermal application of DUL-E1 elastosomal gel. DUL-E1 elastosomes [comprising span®60 and cholesterol (1:1) and brij S2 (edge activator; 5 mg)] were optimum with high E.E.% (81.5 ± 3.2%), small PS (432 ± 13.2 nm), ZP (−30.8 ± 3.3 mV), acceptable Q0.5h (15.6 ± 0.9%), and high Q8h (79.3 ± 3.8%). Intranasal and transdermal DUL-E1 elastosomes revealed significantly higher Cmax (251 ± 18.6 and 248 ± 15.9 ng/mL) at Tmax (2 and 4 h) and improved relative bioavailability (≈ 2.8 and 3.1 folds) respectively, in comparison to oral DUL aqueous solution. In-vivo histopathological studies were conducted to ensure the safety of DUL-E1. Elastosomes are promising novel nano-carriers, capable of enhancing the bioavailability of DUL via various routes of administration.