Duloxetine to prevent neuropathy in breast cancer patients under paclitaxel chemotherapy (a double-blind randomized trial).

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.

Diabetic Neuropathy: A Guide to Pain Management.

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. 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.

PPARγ and AKt gene modulation following pregabalin and duloxetine combination for painful diabetic polyneuropathy.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis. Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed. Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy. Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

Combining medicines to reduce nerve pain in diabetic patientsWhat is this article about? People with diabetes often have nerve pain called diabetic peripheral neuropathy (DPN). Some medicines like pregabalin and duloxetine help, but are not enough. This study tested if using both medicines together works better than using just pregabalin. The study also looked at how these medicines affect certain genes.What were the results? Patients with DPN took either both medicines or just pregabalin for 4 weeks. The combined treatment reduced pain, improved life quality and affected certain genes.What do the results of the study mean? Using pregabalin and duloxetine together can reduce DPN pain more effectively. This offers hope for better treatment options.

Effect of duloxetine on changes in serum proinflammatory cytokine levels in patients with major depressive disorder.

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-1ß (IL-1ß), 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-1ß, 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.

Cognitive improvement in late-life depression treated with vortioxetine and duloxetine in an eight-week randomized controlled trial: The role of age at first onset and change in depressive symptoms.

BACKGROUND: Age at first onset of depression as a clinical factor affecting cognitive improvement in late life depression was investigated. METHODS: 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). RESULTS: 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. LIMITATION: Reliability of clinical history could raise caution as it was collected by subjective recall of patients. CONCLUSION: 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.

Pharmacotherapy in Stress Urinary Incontinence; A Literature Review.

PURPOSE OF REVIEW: Stress urinary incontinence (SUI) is a commonly observed condition in females, as well as in males who have undergone prostatectomy. Despite the significant progress made in surgical techniques, pharmacotherapy has not yielded substantial outcomes within the clinical domain. This review aims to present a comprehensive overview of the existing pharmacotherapy options for stress urinary incontinence (SUI) and the emerging therapeutic targets in this field. RECENT FINDINGS: One meta-analysis demonstrated that α-adrenergic medications are more efficacious in improving rather than curing SUI symptoms. One trial showed reduced pad weight gain with PSD-503, a locally administered α-adrenergic receptor agonist. New data show that duloxetine's risk outweighs its benefits. One small-scale trial was found to support the use of locally administered estriol in improving subjective outcomes. Emerging targets include serotonin 5HT2C agonists, selective inhibitors of norepinephrine uptake, and myostatin inhibitors. Only one of the evaluated drugs, duloxetine, has been approved by some countries. Currently, trials are evaluating novel targets. Systemic adverse effects such as gastrointestinal upset with duloxetine and orthostatic hypotension with α-adrenoceptor agonists have hampered the efficacy of drugs used to treat SUI in women and men.

Duloxetine protected indomethacin-induced gastric mucosal injury by increasing serotonin-dependent RANTES expression and activating PI3K-AKT-VEGF pathway.

Antidepressant duloxetine has been shown protective effect on indomethacin-induced gastric ulcer, which was escorted by inflammation in the gastric mucosa. Cytokines are the principal mediators of inflammation. Thus, by screening the differential expression of cytokines in the gastric mucosa using cytokine array at 3 h after indomethacin exposure, when the gastric ulcer began to format, we found that indomethacin increased cytokines which promoted inflammation responses, whereas duloxetine decreased pro-inflammatory cytokines increased by indomethacin and increased RANTES expression. RANTES was consistently increased by pretreated with both 5 mg/kg and 20 mg/kg duloxetine at 3 h and 6 h after indomethacin exposure in male rats. Selective blockade of RANTES-CCR5 axis by a functional antagonist Met-RANTES or a CCR5 antagonist maraviroc suppressed the protection of duloxetine. Considering the pharmacologic action of duloxetine on reuptake of monoamine neurotransmitters, we examined the serotonin (5-HT), norepinephrine and dopamine contents in the blood and discovered 20 mg/kg duloxetine increased 5-HT levels in platelet-poor plasma, while treatment with 5-HT promoted expression of RANTES in the gastric mucosa and alleviated the indomethacin-induced gastric injury. Furthermore, duloxetine activated PI3K-AKT-VEGF signaling pathway, which was regulated by RANTES-CCR5, and selective inhibitor of VEGF receptor axitinib blocked the prophylactic effect of duloxetine. Furthermore, duloxetine also protected gastric mucosa from indomethacin in female rats, and RANTES was increased by duloxetine after 6 h after indomethacin exposure too. Together, our results identified the role of cytokines, particularly RANTES, and the underlying mechanisms in gastroprotective effect of duloxetine against indomethacin, which advanced our understanding in inflammatory modulation by monoamine-based antidepressants.

Suspected duloxetine-induced restless legs syndrome phenotypic variant: a case report.

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.

The effect of duloxetine on stress urinary incontinence.

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.

Duloxetine and cognitive behavioral therapy with phone-based support for the treatment of chronic musculoskeletal pain: study protocol of the PRECICE randomized control trial.

BACKGROUND: Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. METHODS: Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of three treatment arms: (1) combination treatment (duloxetine + web-based self-guided CBT) with phone-based motivational interviewing (MI), (2) combination treatment without phone-based MI, and (3) duloxetine monotherapy. Participants will be in the study for 24 weeks and will be assessed at baseline, week 13, and week 25. The primary outcome is the Brief Pain Inventory (BPI)-Global Pain Severity score, which combines BPI pain severity and BPI pain interference. Secondary measures include between-group comparisons in mean BPI pain severity and BPI pain interference scores. Data collection and outcome assessment will be blinded to treatment group assignment. DISCUSSION: This randomized controlled trial (RCT) will determine if combination treatment with duloxetine and web-based CBT is superior to duloxetine monotherapy for the management of CMP. Furthermore, this RCT will determine the effectiveness of phone-based motivational interviewing in promoting the continued practice of pain coping skills, thereby enhancing treatment outcomes. TRIAL REGISTRATION: NCT04395001 ClinicalTrials.gov. Registered on May 15, 2020.

Simultaneous measurement of duloxetine hydrochloride and avanafil at dual-wavelength using novel ecologically friendly TLC-densitometric method: application to synthetic mixture and spiked human plasma with evaluation of greenness and blueness.

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.

Duloxetine and Cognitive Behavioral Therapy with Phone-based Support for the Treatment of Chronic Musculoskeletal Pain: Study Protocol of the PRECICE Randomized Control Trial.

Background: Chronic musculoskeletal pain (CMP) is the most common, disabling, and costly of all pain conditions. While evidence exists for the efficacy of both duloxetine and web-based cognitive behavioral therapy (CBT) as monotherapy, there is a clear need to consider study of treatment components that may complement each other. In addition, given the reported association between patient's adherence and treatment outcomes, strategies are needed to enhance participant's motivation to adopt and maintain continued use of newly learned pain coping skills from CBT. Methods: Two hundred eighty participants will be recruited from the primary care clinics of a large academic health care system in North Carolina. Participants with CMP will be randomized to one of 3 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. Registered in ClinicalTrials.gov on May 15, 2020.

Efficacy of patient education and duloxetine, alone and in combination, for patients with multisystem functional somatic disorder: Study protocol for the EDULOX trial.

BACKGROUND: Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. METHODS: This is a nested study design. The parent trial "EDULOX1" (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, "EDULOX2" (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. CONCLUSION: The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education. Trial registration number The study is registered at www. CLINICALTRIALS: gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.

Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression.

Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been effective targeted therapies for non-small cell lung cancer (NSCLC), most advanced NSCLC inevitably develop resistance to these therapies. Combination therapies emerge as valuable approach to preventing, delaying, or overcoming disease progression. Duloxetine, an antidepressant known as a serotonin-noradrenaline reuptake inhibitor, is commonly prescribed for the treatment of chemotherapy-induced peripheral neuropathy. In the present study, we investigated the combined effects of duloxetine and EGFR-TKIs and their possible mechanism in NSCLC cells. Compared with either monotherapy, the combination of duloxetine and EGFR-TKIs leads to synergistic cell death. Mechanistically, duloxetine suppresses 70-kDa ribosomal protein S6 kinase 1 (p70S6K1) activity through mechanistic target of rapamycin complex 1 (mTORC1), and this effect is associated with the synergistic induction of cell death of duloxetine combined with EGFR-TKIs. More importantly, activating transcription factor 4 (ATF4)-induced regulated in development and DNA damage response 1 (REDD1) is responsible for the suppression of mTORC1/S6K1 activation. Additionally, we found that the combination effect was significantly attenuated in REDD1 knockout NSCLC cells. Taken together, our findings reveal that the ATF4/REDD1/mTORC1/S6K1 signaling axis, as a novel mechanism, is responsible for the synergistic therapeutic effect of duloxetine with EGFR-TKIs. These results suggest that combining EGFR-TKIs with duloxetine appears to be a promising way to improve EGFR-TKI efficacy against NSCLC.

Antifungal and antibiofilm effect of duloxetine hydrochloride against Cryptococcus neoformans and Cryptococcus gattii.

Cryptococcosis is an invasive mycosis caused mainly by Cryptococcus gattii and C. neoformans and is treated with amphotericin B (AMB), fluconazole and 5-fluorocytosine. However, antifungal resistance, limited and toxic antifungal arsenal stimulate the search for therapeutic strategies such as drug repurposing. Among the repurposed drugs studied, the selective serotonin reuptake inhibitors (SSRIs) have shown activity against Cryptococcus spp. However, little is known about the antifungal effect of duloxetine hydrochloride (DH), a selective serotonin and norepinephrine reuptake inhibitor (SSNRI), against C. neoformans and C. gattii. In this study, DH inhibited the growth of several C. neoformans and C. gattii strains at concentrations ranging from 15.62 to 62.50 µg/mL. In addition, DH exhibited fungicidal activity ranging from 15.62 to 250 µg/mL. In biofilm, DH treatment reduced Cryptococcus spp. biomass at a level comparable to AMB, with a significant reduction (85%) for C. neoformans biofilms. The metabolic activity of C. neoformans and C. gattii biofilms decreased significantly (99%) after treatment with DH. Scanning electron micrographs confirmed the anti-biofilm activity of DH, as isolated cells could be observed after treatment. In conclusion, DH showed promising antifungal activity against planktonic cells and biofilms of C. neoformans and C. gattii, opening perspectives for further studies with DH in vivo.

Environmentally benign first derivative synchronous spectrofluorimetry for the analysis of two binary mixtures containing duloxetine with avanafil or tadalafil in spiked plasma samples.

Antidepressants can cause sexual dysfunction side effects, necessitating the co-administration of phosphodiesterase type 5 inhibitors. The simultaneous determination of these drugs in biological fluids is critical for therapeutic drug monitoring. For the first time, two binary mixtures containing duloxetine with either avanafil or tadalafil were estimated utilizing simple green spectrofluorimetric methods without the need for a previous separation step. The study was based on first derivative synchronous spectrofluorimetry in ethanol using a change in wavelength difference (∆λ) of 20 and 25 nm for the first and second combinations, respectively. Duloxetine and avanafil were estimated at 297.7 and 331 nm in their binary mixture, while duloxetine and tadalafil were determined at 290.3 and 297.7 nm, respectively. The linearity was achieved over the ranges of 0.1-1.5 µg mL-1 for both duloxetine and avanafil and 0.01-0.40 µg mL-1 for tadalafil, with limits of detection of 0.013, 0.022, and 0.004 µg mL-1 for duloxetine, avanafil, and tadalafil, respectively. Successful application of the developed approaches was accomplished for the estimation of the two mixtures in dosage forms as well as human plasma with excellent percentage recoveries (96-103.75% in plasma), which supports their suitability for use in quality control laboratories and pharmacokinetic studies. Moreover, the adopted approaches' greenness was evidenced by applying three tools.

Antineuropathic Pain Management After Orthopedic Surgery: A Systematic Review.

Background: The opioid crisis has become a present concern in the medical field. In an effort to address these complications, antineuropathic pain medications have been considered as alternatives to prescribed opioids. Objective: This review focuses on the analgesic effects of neuromodulators, such as gabapentin, duloxetine, and pregabalin, that provide room for less dependence on narcotic analgesics following orthopedic surgery. Methods: During the database searches, 1,033 records were identified as a preliminary result. After duplicates were removed, an initial screen of each article was completed which identified records to be removed due to absence of a full-text article. Articles were excluded if they were not either prospective or retrospective, showcased an irrelevant medication (such as tricyclic antidepressants) which are not pertinent to this review, or deemed to be unrelated to the topic. Results: Ultimately, 19 articles were selected. Three different drugs, gabapentin, pregabalin, and duloxetine, were analyzed to compile data on the effectiveness of preventing opioid overuse and addiction following hand surgery. This review identifies potential evidence that peri-operative gabapentin, pregabalin, and duloxetine administration decreases post-operative pain and lowers opioid dependency. Conclusion: Gabapentin, pregabalin, and duloxetine have potential to further decrease post-operative pain and lower opioid dependency. This review creates an opening for further research in hand surgery to assess an updated protocol for pain management to reduce opioid dependency.

Comparative Study of the Effects of Duloxetine and Venlafaxine on Acute Symptomatic Taxane-induced Neuropathy in Breast Cancer Patients: A Randomized Clinical Trial.

Introduction: Chemotherapeutic agents have the potential to induce neurotoxicity, resulting in a range of symptoms, including mild paresthesia, neuropathic pain, pronounced ataxia, and significant impairment. Taxane-induced neuropathy (TIN) is a prevalent adverse effect and a significant constraint of Taxane-based chemotherapy protocols in treating breast cancer. In this current study, we aim to compare the effects of Venlafaxine and Duloxetine in taxane-induced Neuropathy as well as the quality of life, Depression, and Anxiety in Breast cancer Patients. Methods: The present study investigated breast cancer patients who experienced acute neuropathic pain after receiving paclitaxel treatment, a chemotherapeutic agent. The participants were allocated randomly into two groups, one receiving Venlafaxine and the other receiving Duloxetine. The participants underwent assessments for anxiety, depression, pain, neuropathy, quality of life, and neuropathic pain through the administration of questionnaires at the commencement of the study and after ten weeks following the intervention. Results: Both groups exhibited decreased neuropathic pain, with the venlafaxine group significantly reducing McGill's pain score. Although, the result is not suggestive of a difference between venlafaxine and duloxetine impact on any variables scores. Conclusion: Duloxetine and Venlafaxine effectively treat neuropathic symptoms such as paraesthesia, tingling, and itching. Venlafaxine is also beneficial for relieving pain associated with neuropathy.This trial was retrospectively registered on 1.1.2023 at irct.ir (trial registration ID: IRCT20220115053723N1). URL: https://www.irct.ir/trial/62540/pdf.

Simultaneous identification and enantioseparation of ofloxacin and duloxetine without the single standard and computational calculation of their inclusion complexes.

Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R2 ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.

Duloxetine reduces opioid consumption and pain after total hip or knee arthroplasty: a meta-analysis of randomized controlled trials.

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 < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P = 0.02, I2 = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P = 0.02, I2 = 0%). CONCLUSION: Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA.