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Introduction: In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro. Methods: Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7. Results: In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039). Conclusions: The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media. [ABSTRACT FROM AUTHOR]

Background: The escalating number of deaths related to opioid usage has intensified the pursuit of non-opioid alternatives for managing chronic pain. It's often observed that psychiatric comorbidities coexist in patients suffering from chronic pain. There are a variety of psychotropic medications that have demonstrated effectiveness in treating both psychiatric symptoms and pain. This systematic review and meta-analysis aim to assess the effectiveness of various psychiatric drugs in managing specific types of chronic pain, including fibromyalgia, neuropathic pain, and chronic low back pain. Methods: A comprehensive search of five major databases was conducted through February 2023 to identify randomized controlled trials (RCTs) that met our inclusion criteria, focusing on outpatients Over 18 years of age with chronic pain. The study assessed the effectiveness of duloxetine, mirogabalin, pregabalin, gabapentin, and tricyclic antidepressants (TCAs), including serotonin-norepinephrine reuptake inhibitors (SNRIs), across various chronic pain conditions such as fibromyalgia, neuropathic pain, and chronic low back pain. The primary outcome measures included pain reduction, improvement in function, and quality of life. Of the 29 RCTs in the systematic review, 20 studies qualified for the meta-analysis. The analysis was stratified by pain type and treatment duration (short-term ≤14 weeks vs. long-term >14 weeks), using Hedge's g standardized mean differences and a random-effects model, along with sensitivity and subgroup analyses. Results: The overall short-term intervention effect across all studies was significant (SMD -1.45, 95% CI -2.15 to -0.75, p < 0.001), with considerable heterogeneity (I2 = 99%). For fibromyalgia, both duloxetine and mirogabalin demonstrated substantial efficacy with SMDs of -2.42 (95% CI -3.67 to -1.18, p < 0.0001) and -2.10 (95% CI -3.28 to -0.92, p = 0.0005), respectively. Conversely, treatments for neuropathic pain and chronic low back pain, including those with amitriptyline and desipramine, did not show significant benefits. The effectiveness of gabapentin could not be conclusively determined due to limited representation in the data. Additionally, no consistent long-term benefits were observed for any of the medications. Conclusions: While the results of this study underscore the importance of exploring non-opioid alternatives for chronic pain management, particularly in light of the opioid crisis, it is crucial to interpret the findings carefully. Our analysis suggests that certain psychiatric medications, such Duloxetine and mirogabalin demonstrated significant short-term efficacy in fibromyalgia patients. However, their effectiveness in treating neuropathic pain and chronic low back pain was not statistically significant. Additionally, the effectiveness of gabapentin and other medications, such as pregabalin for neuropathic pain, could not be conclusively determined due to limited data and high study heterogeneity. No consistent long-term benefits were observed for any of the drugs studied, raising questions about their sustained efficacy in chronic pain management. These findings highlight the need for further research to understand better the role of psychiatric medications in managing specific chronic pain conditions without prematurely concluding that they are ineffective or unsuitable for these purposes. [ABSTRACT FROM AUTHOR]

A novel, environmentally friendly, and sensitive HPTLC method has been developed and validated for simultaneous quantification of duloxetine (DLX) and tadalafil (TDL) in their pure state, laboratory-prepared mixtures, and spiked human plasma. This method is particularly important for patients dealing with depression and sexual issues, as it allows for the measurement of these co-administered antidepressant and sexual stimulant drugs in biological fluids. The separation process employed a stationary phase of pre-coated silica gel 60 F254 and a mobile phase consisting of ethyl acetate, acetonitrile, and 33% ammonia (8:1:1, v/v). The optimized mobile phase resulted in well-defined bands for DLX and TDL, with Rf values of 0.3 and 0.8, respectively with dual-wavelength detection at 232 nm for DLX and 222 nm for TDL. Polynomial regression analysis revealed exceptional linearity for both drugs, with correlation coefficients of 0.9999 over concentration ranges of 10–900 ng/band for DLX and 10-1200 ng/band for TDL. The quantitation limits were 8.2 ng/band for DLX and 8.6 ng/band for TDL, while the detection limits (LOD) were 2.7 ng/band for DLX and 2.8 ng/band for TDL. The validation of this method followed the guidelines set by the International Council for Harmonization (ICH). Additionally, the suggested method's greenness was assessed by means of four up-to-date ecological tools, namely the Eco-Scale, the National Environmental Method Index (NEMI), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness metric approach (AGREE). The proposed method was also assessed using the Blue Applicability Grade Index (BAGI), a recently developed metric for assessing the practicality (blueness) of procedures. [ABSTRACT FROM AUTHOR]

AbstractPurpose/Aim of the studyMaterials and methodsResultsConclusionsThe pathophysiology of major depressive disorder (MDD) involves multiple factors, including inflammatory processes. This study investigated the relationship between changes in the levels of cytokines and remission in patients with MDD following duloxetine treatment.MDD patients were administered duloxetine for 16 weeks. Clinical evaluation and immunological monitoring were performed every 4 weeks.Our results indicated that changes in serum levels of TNF-α and IL-6 were associated with remission following duloxetine treatment in MDD patients. There was a slight increase in TNF-α levels in the first four weeks following duloxetine treatment, which correlated significantly with patients who were in remission. Furthermore, patients in remission exhibited an initial increase in IL-6 levels in the first four weeks, followed by a decrease at 16 weeks.These results suggest an important relationship between changes in cytokine levels and remission in patients with major depression after duloxetine treatment. [ABSTRACT FROM AUTHOR]

Purpose of Review: Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. Recent Findings: Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Summary: Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Vortioxetine, a multimodal‐acting antidepressant, has recently shown analgesic properties. We aimed to investigate its prophylactic effect in the osteoarthritis (OA) model and gain insights into the underlying molecular mechanisms. Duloxetine was studied as a reference.In the monoiodoacetate (MIA)‐induced rat model of knee OA, pain‐related behaviour was assessed in weight‐bearing and Von Frey tests. Antidepressants were administered orally once daily for 28 days. Gene expression of pain‐related mediators (Ngf, Il‐1β, Tnf‐α, Bdnf, and Tac1 encoding substance P) and oxidative stress parameters were determined after completion of the treatment/behavioural testing protocol.Vortioxetine and duloxetine dose dependently reduced weight‐bearing asymmetry and mechanical hyperalgesia of the paw ipsilateral to the MIA‐injected knee. Vortioxetine reduced the increased Ngf mRNA expression in the MIA‐injected knees to the level in sham‐injected counterparts. It reduced oxidative stress parameters in the affected knees, more effectively in females than males. Duloxetine showed no effect on Ngf mRNA expression and oxidative stress. Both antidepressants decreased mRNA expression of pain‐related mediators in the lumbar L3–L5 ipsilateral DRGs and spinal cords, which were up‐regulated in MIA‐injected rats. This effect was male‐specific.Vortioxetine may be effective against the development of chronic pain in OA. Its antihyperalgesic effect may be mediated, at least in part, by normalization of NGF expression in the affected joint. Decrease of localized oxidative stress and of expression of pain‐related mediators that contribute to central sensitization are also involved in vortioxetine's antihyperalgesic effect, in a sex‐specific pattern. [ABSTRACT FROM AUTHOR]

Age at first onset of depression as a clinical factor affecting cognitive improvement in late life depression was investigated. This is a secondary analysis of an eight-week randomized controlled trial involving 452 elderly patients treated by vortioxetine, duloxetine or placebo (1:1:1). Patients were subcategorized into early-onset (LLD-EO) and late-onset (LLD-LO) groups divided by onset age of 50. Cognitive performance was assessed by composite score of Digit Symbol Substitution Test (DSST) and the Rey Auditory Verbal Learning Test (RAVLT) tasks, while depressive symptoms were assessed by Montgomery–Åsberg Depression Rating Scale (MADRS). Vortioxetine and duloxetine exhibited advantages versus placebo in improving cognitive performance in the LLD-LO group, yet not in the LLD-EO group after eight weeks. Patients in the LLD-EO group showed overall advantage to placebo in depressive symptoms before endpoint (week 8) of treatment, while patients in the LLO-LO group showed no advantage until endpoint. Path analysis suggested a direct effect of vortioxetine (B = 0.656, p =.036) and duloxetine (B = 0.726, p =.028) on improving cognition in the LLD-LO group, yet in all-patients treated set both medications improved cognition indirectly through changes of depressive symptoms. Reliability of clinical history could raise caution as it was collected by subjective recall of patients. Age at first onset might affect cognitive improvement as well as change in depressive symptoms and its mediation towards cognitive improvement in late life depression treated with vortioxetine and duloxetine. • Vortioxetine and Duloxetine improved cognitive performance of elderly depressed patients with first onset after 50. • Patients with first depressive onset before 50 showed earlier symptomatic change than those with first onset after 50. • Vortioxetine and duloxetine showed direct treatment effect on improving cognition in patients with first episode after 50. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and nonmotor symptoms, including depression, which significantly impacts the quality of life of affected individuals. This study aims to investigate the real-world effectiveness and safety of duloxetine in treating comorbid depression in patients with Parkinson's disease and to compare its outcomes with traditional treatment approaches. Methods: This study included adult patients diagnosed with Parkinson's disease combined with depression from December 2020 to December 2023. Based on the use of duloxetine, the cohort was divided into a traditional treatment group and a duloxetine group (traditional treatment combined with duloxetine). Patients with incomplete medical records, concurrent antidepressant therapy, or major psychiatric or neurological disorders were excluded. Retrospective data, including demographic information, treatment adherence, and various assessment scores, were collected from medical records by trained research staff. Results: In total, 106 patients were analyzed, with 50 patients receiving traditional treatment and 56 patients receiving duloxetine. The duloxetine group exhibited significantly lower scores than the traditional treatment group in the Unified PD Rating Scale (p = 0.015), Hamilton Depression Rating Scale (p = 0.013), Beck Depression Inventory (p = 0.031), Parkinson's disease Questionnaire-39 (p = 0.006), and Clinical Global Impression-Improvement (p < 0.001) scores. In motor function assessment, the duloxetine group demonstrated improvements in kinetic tremor scores (p = 0.017), gait speed (p < 0.001), Timed Up and Go Test performance (p < 0.001), dyskinesia severity (p = 0.017), and rigidity (p = 0.019) compared to the traditional treatment group. Additionally, the duloxetine group exhibited better cognitive function across various assessments, including the Symbol Digit Modalities Test (p = 0.024), Stroop Color-Word Test (p = 0.048), and Montreal Cognitive Assessment (p = 0.024). Conclusion: Duloxetine is associated with superior efficacy in improving motor and non-motor symptoms, overall clinical status, and cognitive function. These findings support the potential utility of duloxetine as a comprehensive treatment option for comorbid depression in Parkinson's disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To explore cancer survivors' historical and current use of analgesics for chronic chemotherapy-induced peripheral neuropathy (CIPN). SAMPLE & SETTING: 142 post-treatment cancer survivors who received neurotoxic chemotherapy and were experiencing moderate to severe CIPN. METHODS & VARIABLES: Participants completed the Treatment-Induced Neuropathy Assessment Scale at baseline and reported all analgesics used to manage CIPN. Frequency of historical or current prescription analgesic use for chronic CIPN was described and stratified by CIPN pain severity. RESULTS: At baseline, 31% of participants reported historical use of analgesics for CIPN and 46% of participants were currently using analgesics for CIPN. Gabapentin was the most frequently used analgesic, historically (20%) and currently (34%), and duloxetine was used less frequently (6% historical use, 10% current use). Many participants with severe pain (59%) reported using analgesics for CIPN. IMPLICATIONS FOR NURSING: Duloxetine, the firstline treatment for chronic CIPN pain, was used less frequently than gabapentin, a common prescription analgesic for neuropathic pain. Further research is needed to determine strategies to promote the implementation of evidence-based CIPN treatments in clinical practice. [ABSTRACT FROM AUTHOR]

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The simultaneous occurrence of various pollutants in the aquatic environment raises questions about their mutual interactions. There is a gap in research on the sorption of polar substances on microplastics. This study aimed to assess the adsorption of the antidepressants sertraline, fluoxetine and duloxetine on microplastic polystyrene, polyethylene terephthalate and polyvinyl chloride, each in two versions: virgin and aged. To assess the affinity of the tested drugs for plastic and planktonic organisms, the experiment was conducted in microplastic suspensions and in a mixture of microplastics with the protozoan Spirostomum ambiguum. The Fourier transform infrared technique assessed the identity of microplastics and changes during ageing. No significant differences were found between the sorption of the tested drugs on virgin and aged microplastics. The sorption of sertraline onto microplastics was 1.5–3 times lower in the presence of the protozoa than in samples with microplastics alone. Moreover, its concentration in the protozoan cells was 10–30 times higher than in the microplastics. Considering that the amount of plankton in freshwaters is much greater than that of microplastics, it should be concluded that microplastics have a negligible share in the transport of antidepressants in surface waters. [ABSTRACT FROM AUTHOR]

Purpose To conduct a network meta-analysis comparing the safety and efficacy of gabapentin (GBP), pregabalin (PGB), oxcarbazepine (OXC), and duloxetine (DLX) in treating diabetic peripheral neuropathy (DPN). Materials and Methods The study’s eligibility criteria includee randomized controlled trials (RCTs) with a focus on DPN patients receiving GBP, PGB, DLX, or OXC versus placebo. Noncompliant trials with incomplete information and observational studies were excluded. Results Twelve (RCTs) of PGB, 2 of GBP, 3 of DLX, and 1 of OXC met the inclusion criteria. When drugs were compared for efficacy (direct comparison), GBP (Odd’s ratio [OR] = 3.208, P < 0.001) was most effective followed by OXC (OR = 2.4, P = 0.0248), DLX (OR = 2.346, P < 0.001), and PGB (OR = 2.161, P < 0.001). When drugs were compared for withdrawal due to adverse drug reaction (ADR) (direct comparison), GBP (OR = 1.3818, P = 0.766) was safest followed by PGB (OR = 2.16, P < 0.001), DLX (OR = 2.469, P < 0.001), and OXC (OR = 4.4967, P = 0.001). Indirect comparison was done for efficacy, DLX was statistically significant than PGB and OXC (DLX vs. PGB, P = 0.03; DLX vs. OXC, P = 0.02). When indirect comparison was done for patient withdrawal due to ADR, OXC was worst (GBP vs. OXC, P = 0.0001; PGB vs. OXC, P = 0.007; DLX vs. OXC, P = 0.015). When drugs were compared for individual ADRs (direct comparison), dizziness was most commonly seen with OXC (OR = 9.6535, P = 1.8425), headache with OXC (OR = 3.8686, P = 0.006), somnolence with PGB (OR = 5.189, P < 0.001), and nausea with DLX (OR = 3.264, P < 0.001). GBP was most effective and safest drug followed by OXC > DLX > PGB for efficacy and PGB > DLX > OXC for safety. Conclusion In evaluating medications for DPN against placebo, GBP and OXC demonstrated the highest effectiveness while maintaining a favorable safety profile.

Abstract A novel, environmentally friendly, and sensitive HPTLC method has been developed and validated for simultaneous quantification of duloxetine (DLX) and tadalafil (TDL) in their pure state, laboratory-prepared mixtures, and spiked human plasma. This method is particularly important for patients dealing with depression and sexual issues, as it allows for the measurement of these co-administered antidepressant and sexual stimulant drugs in biological fluids. The separation process employed a stationary phase of pre-coated silica gel 60 F254 and a mobile phase consisting of ethyl acetate, acetonitrile, and 33% ammonia (8:1:1, v/v). The optimized mobile phase resulted in well-defined bands for DLX and TDL, with Rf values of 0.3 and 0.8, respectively with dual-wavelength detection at 232 nm for DLX and 222 nm for TDL. Polynomial regression analysis revealed exceptional linearity for both drugs, with correlation coefficients of 0.9999 over concentration ranges of 10–900 ng/band for DLX and 10-1200 ng/band for TDL. The quantitation limits were 8.2 ng/band for DLX and 8.6 ng/band for TDL, while the detection limits (LOD) were 2.7 ng/band for DLX and 2.8 ng/band for TDL. The validation of this method followed the guidelines set by the International Council for Harmonization (ICH). Additionally, the suggested method’s greenness was assessed by means of four up-to-date ecological tools, namely the Eco-Scale, the National Environmental Method Index (NEMI), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness metric approach (AGREE). The proposed method was also assessed using the Blue Applicability Grade Index (BAGI), a recently developed metric for assessing the practicality (blueness) of procedures.

Abstract Introduction In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro. Methods Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7. Results In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039). Conclusions The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media.

Background. In oncological practice, the study of neuropathic pain syndrome (NPS) in patients receiving chemotherapy (CT) is relevant. This disorder is accompanied by significant motor and autonomic disorders in the upper and lower extremities, which negatively affects the quality of life and daily activity of patients. Aim. To study the formation and evaluation of the effectiveness of NPS therapy in cancer patients with chemo-induced polyneuropathy (CIPN) at various stages of CT. Materials and methods. Sixty three oncological patients with different localization and stage of malignant neoplasm, having NPS and undergoing CT were examined. The average age was 56.3±9.4 years. Most often, patients had cancer of the stomach, breast, and ovaries. The main neurotoxic drugs used in the treatment of the tumor process were oxaliplatin, docetaxel, paclitaxel. The combination therapy was dominated by the carboplatin + paclitaxel scheme. As a therapy for NPS, 31 patients were prescribed a drug with antioxidant activity of azoximer bromide; 32 patients were prescribed duloxetine. The control group included 30 patients with cancer and CIPN who did not receive concomitant symptomatic therapy. Results. During the use of symptomatic therapy, a decrease in the severity of NPS was observed in all patients in the main groups compared with the control group. There was a significant decrease in sensitive disorders, especially in the duloxetine group. In the group of patients receiving azoximer bromide, it was also possible to stabilize the pathological process in the reflex sphere. Conclusion. CIPN and the associated NPS is an iatrogenic complication in cancer patients undergoing CT. Polyneuropathy not only significantly worsens the quality of life of patients, but also leads to a decrease in the effectiveness of treatment due to the need to correct therapeutic regimens. Therefore, early detection, proper monitoring and competent management of CIPN are important aspects of cancer patient care aimed at improving therapy outcomes and the overall well-being of patients.

Abstract Objective Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. Methods A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40–60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. Results Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P 0.05). Conclusions These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1′-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology of CIPN is not completely understood; however, it is believed that chemotherapies induce peripheral neuropathy via directly damaging mitochondria, impairing the function of ion channels, triggering immunological mechanisms, and disrupting microtubules. The treatment of CIPN is a medical challenge, and there are no approved pharmacological options. Currently, duloxetine and other antidepressants, antioxidant, anti-inflammatory, and ion-channel targeted therapies are commonly used in clinics to relieve the symptoms of CIPN. Several other types of drugs, such as cannabinoids, sigma−1 receptor antagonists, and nicotinamides ribose, are being evaluated in preclinical and clinical studies. This paper summarizes the information related to the physiology of CIPN and medicines that could be used for treating this condition. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major side effects and main reasons for affecting quality of life and dose reduction or even discontinuation of treatment in breast cancer patients. One of the most widely prescribed chemotherapies is the "taxanes." Considering that duloxetine has been used in treating neuropathies in recent years, this study aimed to investigate its effectiveness in preventing taxane-related neuropathy. Material and methods: This is a randomized controlled trial on 47 patients: 24 received a placebo and 23 received duloxetine at 30 mg daily in the first week following the injection of paclitaxel and 60 mg during the second week in each chemotherapy cycle. Patients objective (nerve conduction velocity (NCV) values) and subjective symptoms (visual analog scale including; neuropathy, paresthesia, pain, cold sensitivity, and numbness), the grades of the patients' neuropathy (calculated according to Common Terminology Criteria for Adverse Events (CTCAE) v.5), and the presence of complications, before and after each chemotherapy cycle, were recorded. Results: The placebo group experienced significantly higher occurrences of new neuropathy (8/23 in duloxetine vs 16/24 in placebo, P = 0.029) in NCV by tibial nerve latency (− 0.28% vs 19.87%, P = 0.006), tibial amplitude (4.40% vs − 10.88%, P = 0.049), and median nerve latency (8.72% vs 31.16%, P = 0.039); administration of duloxetine significantly reduced the scores of neuropathies (P < 0.001), pain (P = 0.027), during chemotherapy, and 6 weeks later; however, no significant effect was observed on paresthesia, numbness, cold sensitivity, and other NCV measurements. Conclusions: Paclitaxel can cause neuropathy, lasting for a long time. Our study showed duloxetine is potentially an effective medication that can prevent subjective and objective neuropathy. [ABSTRACT FROM AUTHOR]

Rationale: The efficacy and safety of antidepressant augmentation therapy with aripiprazole (AATA) has been established; however, the ongoing effects of continuing aripiprazole after remission remain unclear because no studies have examined this issue. Objectives: We aimed to explore the effect of AATA discontinuation on the major depressive disorder (MDD) recurrence risk in patients with remitted MDD after AATA. Methods: This 24-week, multicenter, placebo-controlled, double-blind, randomized trial evaluated recurrence risk in patients with MDD who achieved remission with AATA. Differences in MDD recurrence, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, between the two groups were compared using survival analysis. The differences in depressive symptom severity and social functioning between the two groups were compared using a mixed model with repeated measures. Extrapyramidal symptoms and akathisia were also assessed. Results: Twenty-three participants were randomized and treated. Two patients in each group experienced recurrence during the study. Kaplan–Meier analysis with Log-rank comparison showed no difference in recurrence between groups (p = 0.642). No significant difference in interactions between group and period was observed in the 17-item Hamilton depression rating scale (p = 0.492) or the Social and Occupational Functioning Assessment Scale (p = 0.638). No patients developed extrapyramidal symptoms or akathisia. Conclusions: Definitive conclusions could not be drawn owing to the small sample size. This study represents a starting point for investigating the safety of aripiprazole discontinuation on recurrence in patients with MDD who have achieved remission with AATA. Future studies with appropriate sample sizes calculated based on this study are needed. [ABSTRACT FROM AUTHOR]

Pain control and patient satisfaction after total knee arthroplasty (TKA) have room for improvement. While studies have reported better analgesic outcomes with antidepressants like duloxetine in patients who do not have central sensitivity (CS), we undertook this trial to determine the short and midterm analgesic role of low-dose duloxetine in patients who do not have CS. This prospective, double-blinded, randomized, placebo-controlled trial was conducted in 106 patients undergoing single-setting, bilateral TKA under spinal anesthesia. There were 2 matched groups, with one given 20 mg of duloxetine and the other given a placebo (similar in appearance and weight) from preoperative day 2 to postoperative day 28. Follow-ups were scheduled at 48-hours, 1-week, 2-weeks, 4-weeks, and 3-months. Pain was measured using a visual analogue scale at rest and visual analogue scale at mobilization (mVAS). Secondary measures included additional non-steroidal anti-inflammatory drug consumption, patient satisfaction, and safety profile. The visual analogue scale at rest in the duloxetine group was better in the first 48 hours (6.38 ± 1.32 versus 7.02 ± 0.99; P =.017), 1-week (4.76 ± 1.24 versus 5.89 ± 1.06; P <.001), and 2-weeks (3.34 ± 1.19 versus 4.26 ± 1.02; P <.001) follow-up. The mVAS remained significantly higher in the duloxetine group in the first 48 hours (7.23 ± 1.12 versus 8.21 ± 0.69; P <.001), 1-week (5.83 ± 1.11 versus 6.82 ± 0.92; P <.001), and 2 weeks (3.70 ± 0.89 versus 4.60 ± 1.03; P <.001) follow-up. Both outcomes became comparable from 4-week follow-up onward. Patient satisfaction (8.44 ± 1.68 versus 7.17 ± 1.04; P <.001) and additional non-steroidal anti-inflammatory drug consumption (2,770 ± 533.05 versus 3,566.04 ± 464.54; P <.001) were better in the duloxetine group, with a comparable safety profile. In patients who did not have CS, persistent pain after bilateral TKA can be managed safely and successfully by a daily dose of 20 mg Duloxetine, improving patient satisfaction and analgesic consumption in the acute postoperative phase. [ABSTRACT FROM AUTHOR]

Depression is a prevalent mental disorder that significantly diminishes quality of life and longevity, ranking as one of the primary causes of disability globally. Contemporary research has explored the potential pathogenesis of depression from various angles, encompassing genetics, neurotransmitter systems, neurotrophic factors, the hypothalamic-pituitary-adrenal axis, inflammation, and intestinal flora, among other contributing factors. In addition, conventional chemical medications are plagued by delayed onset of action, persistent adverse effects, and restricted therapeutic efficacy. In light of these limitations, the therapeutic approach of traditional Chinese medicine (TCM) has gained increasing recognition for its superior effectiveness. Numerous pharmacological and clinical studies have substantiated TCM's capacity to mitigate depressive symptoms through diverse mechanisms. This article attempts to summarize the mechanisms involved in the pathogenesis of depression and to describe the characteristics of herbal medicines (including compounded formulas and active ingredients) for the treatment of depression. It further evaluates their effectiveness by correlating with the multifaceted pathogenesis of depression, thereby furnishing a reference for future research endeavors. [ABSTRACT FROM AUTHOR]

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain. [ABSTRACT FROM AUTHOR]

Background: Health‐related quality of life (HRQL) is an important goal for patients with major depressive disorder (MDD), but whether antidepressants improve HRQL in these patients is unclear. Here, we describe the real‐world effects of trazodone once‐a‐day (TzOAD) and selective serotonin reuptake inhibitor (SSRI) treatments on HRQL and functioning in adults with MDD. Methods: This 8‐week prospective, observational, open‐label, multicenter study was conducted in adults with moderate or severe MDD for whom TzOAD or SSRI were prescribed as monotherapy. The primary outcome was life enjoyment and satisfaction assessed via the patient‐reported Quality‐of‐Life Enjoyment and Satisfaction Questionnaire Short Form (Q‐LES‐Q‐SF) from baseline to week 8. Secondary outcomes included change in Q‐LES‐Q‐SF from baseline to weeks 1 and 2; severity of depressive symptoms using the Montgomery Åsberg Depression Rating Scale (MADRS) and sleep disturbance via the PROMIS SF‐SD 8b questionnaire at weeks 1, 2, and 8; and overall functioning via the Sheehan Disability Scale (SDS), hedonic capacity using the Snaith–Hamilton Pleasure Scale (SHAPS), and cognitive dysfunction using the Perceived Deficits Questionnaire (PDQ‐5) at baseline and week 8. Results: The study included 208 adults with MDD (mean [SD] age = 50.2 [14.3] years; 68.6% female; 98.4% White). Life enjoyment and satisfaction improved from baseline to week 8 for both treatment groups: Q‐LES‐Q‐SF mean (SD) scores were 27.5 (20.4) for the SSRI group and 39.0 (22.1) for the TzOAD group. Depressive symptoms and sleep disturbances also reduced from baseline to week 8: MADRS (SSRI, −15.7 [8.3]; TzOAD, −21.0 [9.8]); PROMIS SF‐SD 8b (SSRI, −9.9 [12.6]; TzOAD, −22.0 [12.6]). Mean change scores in Q‐LES‐Q‐SF, MADRS, and PROMIS SF‐SD 8b improved as early as week 1 in both groups. Mean scores also improved from baseline to week 8 on SDS (SSRI, −9.2 [7.4]; TzOAD, −14.3 [7.5]), SHAPS (SSRI, −6.6 [4.3]; TzOAD, −8.3 [4.4]), and PDQ‐5 (SSRI, −5.8 [4.5]; TzOAD, −7.7 [5.0]). Conclusions: In adults with MDD who received TzOAD or SSRIs, overall and individual HQRL domains improved rapidly and in parallel with improvements in depressive symptoms, with a slightly greater improvement observed in the TzOAD group. [ABSTRACT FROM AUTHOR]

Introduction and Objective. Surgery and anaesthesia are crucial components of healthcare services which significantly reduce the risk of mortality and disability for millions of people worldwide each year. The most common problem occurring after inpatient and outpatient procedures continues to be post-operative pain. One possible way to prevent pain may be the use of co-analgesics such as duloxetine. Review Methods. The PubMed database was searched to gather studies examining the utilization and efficacy of duloxetine in the treatment of post-operative pain. Three search formulations were employed to broaden the scope of results: 'duloxetine and pain and post-operative', 'duloxetine and pain and peri-operative', and 'duloxetine and pain and pre-operative'. Brief description of the state of knowledge. Currently, duloxetine, together with other coanalgesics, is a first-line drug in the treatment of neuropathic pain. The use of peri-operative duloxetine has also been investigated in systemic reviews and meta-analyses. According to current knowledge, duloxetine may have measurable effects in the treatment of pain and reduction of opioid use, but the decision to undertake such treatment should be specific to the patient. Summary. The efficacy of duloxetine administration during the peri-operative period in reducing post-operative pain is contingent upon the nature of the surgical intervention and the therapeutic protocol employed. The documented benefits underscore the importance of pursuing additional research efforts. [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. Methods: A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1β (IL-1β), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40–60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. Results: Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1β, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05). Conclusions: These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of carbamazepine and duloxetiene for the treatment of diabetic neuropathy. Study Design: Single-center study. Setting: Services Hospital, Lahore. Period: 15-08-2023 to 20-11-23. Methods: It involved 100 participants split into two groups, with one group receiving 60 mg daily of duloxetine and the other group taking oral carbamazepine (CBZ) twice daily at a recommended daily dose of 400 mg. CBZ dosing began at 100 mg on the first day and was gradually increased to 400 mg by the end of the first week (days 6 and 7). Subsequent dose adjustments, up to a maximum of 800 mg daily, were determined based on individual clinical responses and tolerability. Participants were followed for 12 weeks, during which changes in neuropathic pain were compared to baseline using a comprehensive pain severity score. This score was calculated by averaging pain intensity ratings at its most severe, least severe, average, and specific time points. Results: In the CBZ and Duloxetiene group, the mean VAS score at baseline was 5.38+0.49 and 5.40+0.49 which reduced after 12 weeks of treatment to 3.26+0.44 in CBZ and 3.82+0.89 in Duloxetiene group, (P<0.001). Conclusion: Treatment with carbamazepine for neuropathic pain in adults with diabetes for 12 weeks demonstrated a substantial pain-relieving benefit, with lower mean pain intensity compared to treatment with Duloxetiene 60 mg/daily, in this real-world experience trial. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the influencing factors of blood concentration / dose ratio (C / D) after oral administration of duloxetine in patients with depression, so as to provide reference for clinical implementation of individualized medication. METHODS: A total of 264 samples of blood concentration monitoring data of inpatients receiving duloxetine in our hospital from 2020 to 2022 were retrospectively collected, the effects of gender, age, nationality, body mass index ( BMI), complicating disease, drug combination, drug manufacturer and smoking on C / D value of duloxetine were analyzed. RESULTS: The mean daily dose of duloxetine was (54. 55±13. 10) mg / d, the mean steady-state blood concentration was ( 69. 14 ± 22. 87) ng / mL, and the mean C / D value was ( 1. 44 ± 0. 62) ng·d / (mL·mg). The C / D value of duloxetine in female patients was significantly higher than that in male patients (P<0. 05); the C / D value of duloxetine in patients of Hui nationality was significantly higher than those of Kazak nationality (P<0. 01); the C / D value of duloxetine in normal group (BMI from 18. 5 to <24. 0) and overweight group (BMI from 24. 0 to <28. 0) were higher than that in obese group (BMI ≥28. 0) (P<0. 05); the C / D value of duloxetine in patients received drug combination of olanzapine and trazodone were higher than that of quetiapine (P< 0. 05); the C / D value of duloxetine in patients complicated with hypertension was higher than that with no complicating disease (P<0. 05), the differences were statistically significant. There was no correlation between drug manufacturers and the C / D value of duloxetine (P>0. 05), the correlation between age and smoking and the C / D value of duloxetine still needed to be verified by further expanding sample size. CONCLUSIONS: Duloxetine has large inter-individual pharmacokinetic differences, the gender, nationality, BMI, complicating disease and drug combination can cause fluctuations in blood concentration of duloxetine, therefore, clinicians or pharmacists should adjust and optimize the individual dosing regimen in combination with patient’s blood concentration and clinical efficacy in time. [ABSTRACT FROM AUTHOR]

Aims: To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. Methods: Eligible patients in Japan (aged 18–59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self‐reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9‐item (PHQ‐9), Generalized Anxiety Disorder 7‐item (GAD‐7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5‐Dimension 5‐Levels questionnaire (EQ‐5D‐5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. Results: In total, 3376 patients were included in the analysis (56% male; 48% aged 50–59 years). Overall, 67.1% of patients self‐reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ‐9, GAD‐7, WSAS, and EQ‐5D‐5L scores (correlation coefficients: 0.67, 0.55, 0.56, −0.51, respectively; all p < 0.0001). Descriptive analyses showed that one‐third of patients reporting EB symptoms did not tell their physician, with two‐thirds finding these symptoms distressing and likely to affect recovery. Conclusion: EB is an important clinical issue in Japan that needs to be considered alongside functional recovery when managing treatment of patients with MDD. [ABSTRACT FROM AUTHOR]

Specific selective serotonin reuptake inhibitors (SSRIs) metabolism is strongly influenced by two pharmacogenes, CYP2D6 and CYP2C19. However, the effectiveness of prospectively using pharmacogenetic variants to select or dose SSRIs for depression is uncertain in routine clinical practice. The objective of this prospective, multicenter, pragmatic randomized controlled trial is to determine the effectiveness of genotype‐guided selection and dosing of antidepressants on control of depression in participants who are 8 years or older with ≥3 months of depressive symptoms who require new or revised therapy. Those randomized to the intervention arm undergo pharmacogenetic testing at baseline and receive a pharmacy consult and/or automated clinical decision support intervention based on an actionable phenotype, while those randomized to the control arm have pharmacogenetic testing at the end of 6‐months. In both groups, depression and drug tolerability outcomes are assessed at baseline, 1 month, 3 months (primary), and 6 months. The primary end point is defined by change in Patient‐Reported Outcomes Measurement Information System (PROMIS) Depression score assessed at 3 months versus baseline. Secondary end points include change inpatient health questionnaire (PHQ‐8) measure of depression severity, remission rates defined by PROMIS score < 16, medication adherence, and medication side effects. The primary analysis will compare the PROMIS score difference between trial arms among those with an actionable CYP2D6 or CYP2C19 genetic result or a CYP2D6 drug–drug interaction. The trial has completed accrual of 1461 participants, of which 562 were found to have an actionable phenotype to date, and follow‐up will be complete in April of 2024. [ABSTRACT FROM AUTHOR]

ObjectiveAlthough quetiapine has been approved for use in schizophrenic patients, its individualized dosage regimen remains unclear, especially with respect to drug–drug interactions (DDIs). Thus, we investigated the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on population pharmacokinetics (PPK).MethodsNinety-six schizophrenic patients treated with quetiapine were included to establish the PPK model, which also includes coadministration of multiple drugs.ResultsIt was found that the patient weights and fluvoxamine or duloxetine coadministration affected quetiapine clearance in schizophrenic patients. Without fluvoxamine or duloxetine coadministration, 16 and 12 mg/kg/day of quetiapine were recommended to schizophrenic patients whose weights were in the ranges of 40–50 and 50–120 kg, respectively. With fluvoxamine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the range of 40–120 kg. With duloxetine coadministration, 8 mg/kg/day of quetiapine was recommended to patients with weights in the 40–120 kg range. With simultaneous coadministration of fluvoxamine and duloxetine, 4 mg/kg/day of quetiapine was recommended to patients with weights in the 40–120 kg range.ConclusionThe present study was a pilot effort at investigating the potential DDIs and optimal initial dosage of quetiapine in schizophrenic patients based on PPK. The initial dosages of quetiapine administered to the patients were optimized according to the coadministration of fluvoxamine or duloxetine.

Obsessive-compulsive disorder (OCD) is the fourth most common psychiatric disorder with a significant morbidity rate. Despite various treatment modalities and medications, some patients show no definitive response. The aim of this study is to classify the medications of OCD with machine learning (ML) methods and to compare the classification performances of the decision tree (DT), chi-square automatic interaction detection (CHAID) algorithm, and linear model in ML methods. This research is a descriptive analytical study based on co-word and artificial intelligence methods. The DT models were created with a target (total weight link strength). For hyperparameter optimization, the Gini index was used as the weight total link strength. The performance of the DT model was evaluated based on the prediction model. A total of 116 drugs were extracted from 6574 articles based on co-word analysis, and 56 drugs were classified as the DT's root. These drugs were categorized into six groups in the EWKM diagram. The DT was constructed using the weight.total.link index, with 7 items in Label 3 and 42 items in Label 5 serving as DT leaves. The ML analysis provided valuable insights into the efficacy of various medications such as clomipramine, duloxetine, and pindolol, as well as supplements such as folate, in the treatment of OCD. Treating concomitant diseases, namely hypothyroidism and streptococcal infection could improve the efficacy of treatment.

The aim of this study is to investigate novel strategies for reducing adverse reactions caused by erdafitinib through a drug combination based on its pharmacokinetic characteristics. The spectrum and characterizations of drugs that can inhibit the metabolism of erdafitinib are examined both in vitro and in vivo. The efficacy of combination regimens are then evaluated using subcutaneous xenograft tumor models. The results demonstrated that sertraline and duloxetine, out of more than 100 screened drugs, inhibited the metabolism of erdafitinib through mixed and non-competitive inhibition, respectively. This inhibition primarily occurred via the CYP2C9 and CYP2D6 pathways. The primary alleles of CYP2C9 and CYP2D6 not only determine the metabolic characteristics of erdafitinib but also influence the strength of drug-drug interactions. Co-administration of sertraline or duloxetine with erdafitinib in rats and mice resulted in nearly a three-fold increase in the blood exposure of erdafitinib and its major metabolite M6. When sertraline or duloxetine was combined with 1/3 of the erdafitinib dosage, the anti-proliferative and pro-apoptotic effects on SNU-16 xenografts were comparable to those of the original full dose of erdafitinib. However, the combination regimen significantly mitigated hyperphosphatemia, retinal damage, intestinal villus damage, and gut microbiome dysbiosis. This study utilized pharmacokinetic methods to propose a new formulation of erdafitinib combined with sertraline or duloxetine. The findings suggest that this combination has potential for clinical co-administration based on a database analysis, thereby providing a novel strategy for anti-tumor treatment with fibroblast growth factor receptor (FGFR) inhibitors.

The article focuses on a study comparing weight gain risk across eight commonly used antidepressants, finding bupropion associated with the least weight gain and varying weight effects for other drugs over 6, 12, and 24 months.

BackgroundDuloxetine is a Food and Drug Administration-approved selective norepinephrine reuptake inhibitor for treating depression, anxiety, fibromyalgia, and neuropathic and chronic musculoskeletal pain. This meta-analysis aims to evaluate the efficacy of duloxetine in reducing pain and postoperative opioid use following lower extremity total joint arthroplasty.MethodsA literature search was performed, identifying randomized controlled trials investigating duloxetine for pain management after total hip and total knee arthroplasty. Data from the visual analog scale (VAS) for pain during movement and at rest were extracted for postoperative days (PODs) 1, 3, 7, and 14, as well as postoperative week 6 and postoperative month 3. Opioid use data were obtained at 24, 48 and 72 hours. All data were analyzed using inverse variance with random effects and presented as weighted mean difference.ResultsEight unique studies were identified and included, 7 of which were analyzed quantitatively. Duloxetine decreased postoperative opioid consumption at 48 and 72 hours. For VAS for pain at rest, significantly reduced pain was reported by duloxetine-treated patients at POD 3, POD 7, and postoperative week 6. For VAS for pain at movement, significantly reduced pain was reported by duloxetine-treated patients at POD1, POD 3, POD 7, POD 14, postoperative week 6, and postoperative month 3.ConclusionsDuloxetine appears to decrease postoperative pain and opioid consumption following total joint arthroplasty. However, definitive conclusions are limited by small sample size and study heterogeneity. While there is a need for follow-up studies to determine the optimal dose, duration, and patient population, strong preliminary data provide robust support for future large-scale efficacy studies.

Abstract 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.

Abstract Background Restless arms syndrome (RAS) is the most common variant of restless legs syndrome (RLS), which is easy to be ignored in clinical practice due to the lack of specific diagnostic criteria. When effective therapeutic agents induced RAS and symptoms persisted after briefly observation, clinicians will face the challenge of weighing efficacy against side effects. Case presentation A 67-year-old woman was admitted to a geriatric psychiatric ward with depression. Upon admission, the escitalopram dose was reduced from 15 mg to 10 mg per day, and the duloxetine dose was increased from 60 mg to 80 mg per day. The next night before bedtime, she developed itching and creeping sensations deep inside bilateral shoulders and arms, with the urge to move, worsening at rest, and alleviation after hammering. The symptoms persisted when escitalopram was discontinued. A history of RLS was confirmed. Treatment with 40 mg of duloxetine and 0.125 mg of pramipexole significantly improved depression, and the paresthesia disappeared, with no recurrence occurring 6 months after discharge. Discussion and conclusions This case suggests that psychiatrists should pay attention to RLS variants when increasing doses of duloxetine. Long-term improvement can be achieved through dosage reduction combined with dopaminergic drugs instead of immediate discontinuation.

Abstract The simultaneous assay of duloxetine hydrochloride (DLX) and avanafil (AVN) in their pure forms, synthetic mixtures, and spiked human plasma was achieved using a novel, eco-friendly, sensitive, and specific HPTLC methodology that have been established and validated. Measuring the levels of co-administered antidepressants and sexual stimulants in biological fluids is an important step for individuals with depression and sexual problems. Separation was performed successfully using pre-coated silica gel 60-F254 as a stationary phase and a mobile phase composed of methanol, acetone, and 33% ammonia (8:2:0.05, v/v/v). Compact bands were produced by the optimized mobile phase that was chosen for development (Rf values were 0.23 and 0.75 for DLX and AVN, individually) after dual-wavelength detection for DLX and AVN at 232 and 253 nm, respectively. The results of polynomial regression analysis were exceptional (r = 0.9999 for both medicines) over concentration ranges of 5-800 and 10-800ng/spot for DLX and AVN, respectively. The quantitation limits were 4.69 and 9.53 ng/spot (0.31 and 0.94 µg/mL), whereas the detection limits were 1.55 and 3.15 ng/spot (0.63 and 1.91 µg/mL), for DLX and AVN, respectively. The International Council for Harmonization (ICH) criteria served as the basis for validating the established approach. Moreover, the proposed technique was evaluated in terms of greenness using four contemporary ecological metrics: The Analytical Greenness software (AGREE), the Green Analytical Procedure Index (GAPI), Eco-Scale, and the National Environmental Method Index (NEMI). Additionally, the Blue Applicability Grade Index (BAGI), a newly developed tool for evaluating the practicality (blueness) of procedures, was taken into consideration when evaluating the sustainability levels of the established approach.

Abstract Purpose There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA. Methods As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions. Results Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = − 0.50, 95% confidence intervals [CI]: −0.70 to − 0.31, P

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. [ABSTRACT FROM AUTHOR]

The simultaneous assay of duloxetine hydrochloride (DLX) and avanafil (AVN) in their pure forms, synthetic mixtures, and spiked human plasma was achieved using a novel, eco-friendly, sensitive, and specific HPTLC methodology that have been established and validated. Measuring the levels of co-administered antidepressants and sexual stimulants in biological fluids is an important step for individuals with depression and sexual problems. Separation was performed successfully using pre-coated silica gel 60-F254 as a stationary phase and a mobile phase composed of methanol, acetone, and 33% ammonia (8:2:0.05, v/v/v). Compact bands were produced by the optimized mobile phase that was chosen for development (Rf values were 0.23 and 0.75 for DLX and AVN, individually) after dual-wavelength detection for DLX and AVN at 232 and 253 nm, respectively. The results of polynomial regression analysis were exceptional (r = 0.9999 for both medicines) over concentration ranges of 5-800 and 10-800ng/spot for DLX and AVN, respectively. The quantitation limits were 4.69 and 9.53 ng/spot (0.31 and 0.94 µg/mL), whereas the detection limits were 1.55 and 3.15 ng/spot (0.63 and 1.91 µg/mL), for DLX and AVN, respectively. The International Council for Harmonization (ICH) criteria served as the basis for validating the established approach. Moreover, the proposed technique was evaluated in terms of greenness using four contemporary ecological metrics: The Analytical Greenness software (AGREE), the Green Analytical Procedure Index (GAPI), Eco-Scale, and the National Environmental Method Index (NEMI). Additionally, the Blue Applicability Grade Index (BAGI), a newly developed tool for evaluating the practicality (blueness) of procedures, was taken into consideration when evaluating the sustainability levels of the established approach. [ABSTRACT FROM AUTHOR]

Chronic orofacial pain (COP) is relieved by duloxetine (DLX) and frequently causes depressive symptoms. The aim of this study was to confirm effects of DLX on pain and depressive symptoms, and to associate with their effectiveness in platelet serotonin transporter (SERT) expression, which is a target molecule of DLX and plasma serotonin concentration in COP patients with depressive symptoms. We assessed for the severity of pain and depressive symptoms using the Visual Analog Scale (VAS) and 17-item Hamilton Depression Rating Scale (HDRS), respectively. Chronic orofacial pain patients were classified into 2 groups based on their HDRS before DLX-treatment: COP patients with (COP-D) and without (COP-ND) depressive symptoms. We found that the VAS and HDRS scores of both groups were significantly decreased after DLX treatment compared with those before DLX treatment. Upregulation of total SERT and downregulation of ubiquitinated SERT were observed before DLX treatment in both groups compared with healthy controls. After DLX treatment, there were no differences in total SERT of both groups and in ubiquitinated SERT of COP-D patients compared with healthy controls; whereas, ubiquitinated SERT of COP-ND patients remained downregulated. There were positive correlations between changes of serotonin concentrations and of VAS or HDRS scores in only COP-D patients. Our findings indicate that DLX improves not only pain but also comorbid depressive symptoms of COP-D patients. Duloxetine also reduces platelet SERT through upregulation of ubiquitinated SERT. As the result, decrease of plasma serotonin concentrations may be related to the efficacy of DLX in relieving pain and depression in COP patients. [ABSTRACT FROM AUTHOR]

Background: Diabetes Mellitus (DM) is a chronic metabolic disorder that causes neuropathy. Diabetic neuropathy causes severe pain and needs therapy to relieve its pain. In Indonesia, the therapy uses paracetamol, sometimes combined with acupressure. However, the efficacy of the combination therapy needs to be better understood. Purpose: This study aimed to elucidate the efficacy of paracetamol vs paracetamol combined with acupressure for pain relief in diabetic neuropathy patients. Materials and methods: This study used a cross-sectional study design. Total of 70 participants were agreed to involved in this study. The patients were then interviewed, and their visual analogue scale was assessed. The data was then analysed statistically using Pearson's correlation. Result: Out of the 70 patients diagnosed with type II DM, 40 had Diabetic Neuropathic Pain (DNP). Shockingly, most of the patients with type II DM and DNP were females, accounting for 33 out of 40 cases (82.50%). The study found a significant correlation between the type of therapy and the decrease in VAS scores for diabetic patients with neuropathic pain (p=0.05). Patients treated with paracetamol and acupressure showed more improvement in the VAS score than those treated with only paracetamol. Conclusion: The study suggests that the combination treatment could benefit DNP as an analgesic for type II DM patients. Advanced study is required to be performed using larger samples so that accurate data can be obtained. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aims to evaluate the effect of duloxetine on stress urinary incontinence (SUI) episode frequency (IEF) per week IEF. Methods: In this clinical trial, 100 women aged 20−80 years with urinary incontinence were assessed based on the standard questionnaire of urinary tract disorders. All the patients received a placebo for 2 weeks. Patients were then randomly divided into two groups of 50 patients each, receiving duloxetine (40 mg twice a day for 12 weeks) and placebo. The two groups were compared in terms of IEF and the mean score of quality of life and side effects. Results: The two groups of duloxetine and placebo recipients were matched at the beginning of the study in terms of age, BMI, IEF, parity, and type of delivery. IEF significantly decreased in the duloxetine recipient group compared to the placebo group. The mean score of quality of life in the duloxetine recipient group increased significantly. The rate of study abandonment in the duloxetine recipient group was significantly higher than in the placebo group. Vertigo was the most common complication that caused patients to discontinue the use of the drug. Conclusion: Duloxetine is therapeutically effective for SUI in women. Patients should be provided information regarding potential side effects and their management. [ABSTRACT FROM AUTHOR]

Objectives: To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD). Methods: We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events. Results: Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies. Conclusions: A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies. [ABSTRACT FROM AUTHOR]