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Steroids Oct 2023Allopregnanolone (AP) is a neurosteroid synthesized in the brain and a positive allosteric modulator of γ-aminobutyric acid (GABA) type A receptors. Some drugs...
Drugs possessing aryloxypropanamine pharmacophore, duloxetine, dapoxetine and propranolol, increase allopregnanolone in rat brain: Possible involvement of allopregnanolone in their central nervous system effects.
Allopregnanolone (AP) is a neurosteroid synthesized in the brain and a positive allosteric modulator of γ-aminobutyric acid (GABA) type A receptors. Some drugs possessing the aryloxypropanamine (AOPA) pharmacophore, such as fluoxetine, exert their central nervous system (CNS) effects by increasing the brain AP. Although duloxetine (DLX), dapoxetine (DPX), atomoxetine (ATX) and propranolol (PRL) also possess the AOPA pharmacophore and are used to treat some psychiatric disorders, the capabilities of these drugs to increase the brain AP and the possible involvement of AP in their CNS effects remain to be fully elucidated. To clarify these points, we first developed a method for quantifying AP in the rat brain by liquid chromatography/electrospray ionization-tandem mass spectrometry. Analysis of the changes in the brain AP levels using this method revealed that the intraperitoneal administration of DLX (10 mg/kg), DPX (10 mg/kg) and PRL (20 mg/kg) significantly increased the brain AP (DLX: < 0.40-2.74 ng/g tissue, DPX: 1.48-3.83 ng/g tissue and PRL: < 0.40-2.09 ng/g tissue) compared to the saline administration (<0.40 ng/g tissue). These results suggested the possible involvement of the GABAergic neurosteroid, AP, in the central actions of DLX, DPX and PRL. In contrast, ATX (10 mg/kg) did not affect the AP levels in the brain. In addition, the brain and serum AP levels had a remarkably high positive correlation after the administration of DLX, DPX and PRL. Thus, this study proposed the AP-related novel mechanism of actions of DLX, DPX and PRL in the CNS.
Topics: Animals; Rats; Brain; Duloxetine Hydrochloride; Neurosteroids; Pharmaceutical Preparations; Pharmacophore; Pregnanolone; Propranolol; Propylamines
PubMed: 37468115
DOI: 10.1016/j.steroids.2023.109272 -
AAPS PharmSciTech Jul 2023The aim of the study was to develop and optimise drug-in-adhesive (DIA) transdermal patch of duloxetine HCl for enhanced drug delivery. DIA patch so developed reduced...
The aim of the study was to develop and optimise drug-in-adhesive (DIA) transdermal patch of duloxetine HCl for enhanced drug delivery. DIA patch so developed reduced the dose and dosing frequency by enhancing bio-performance of the drug. A transdermal DIA patch having Duro-Tak 87-2287 as DIA polymer and Transcutol P as permeation enhancer loaded with 40% drug previously complexed with MeβCD duly characterised (FTIR, DSC, and SEM) was developed for in vivo study. Pharmacokinetic parameters of developed formulation were assessed and compared with oral route of administration. Among various permeation enhancers (PEs), Transcutol P exhibited most enhanced permeation (ER ≈ 1.99) in terms of flux and Q compared to control group having. Mean of maximum plasma concentration (C) and area under time-concentration curve (AUC) in Wistar rats (n = 6) for transdermal patch (10 mg/kg) was found to be 70.31 ± 11.2 ng/ml and 2997.29 ± 387.4 ng/ml*h, respectively, and were considerably higher than oral dose of DLX (20 mg/kg and 10 mg/kg). Albeit, T was higher in case of transdermal delivery, but this was due to sustained behaviour of delivery system. These findings highlight the significance of both inclusion complexation and transdermal delivery of DLX using DIA patch for efficient drug absorption.
Topics: Rats; Animals; Skin Absorption; Duloxetine Hydrochloride; Rats, Wistar; Administration, Cutaneous; Adhesives; Transdermal Patch; Skin
PubMed: 37466741
DOI: 10.1208/s12249-023-02607-7 -
International Journal of Surgery... Nov 2023
Topics: Humans; Arthroplasty, Replacement, Knee; Duloxetine Hydrochloride; Osteoarthritis, Knee; Treatment Outcome
PubMed: 37463005
DOI: 10.1097/JS9.0000000000000618 -
Journal of Orthopaedic Surgery and... Jul 2023The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The optimal dose of duloxetine in the management of fibromyalgia remains still controversial. Therefore, a systematic review and meta-analysis to investigate efficacy and safety of duloxetine was conducted. The outcomes of interests were to assess changes in Fibromyalgia Impact Questionnaire (FIQ), Brief Pain Inventory (BPI), and Clinical Global Impression (CGI). The rate of of adverse events and those leading to therapy discontinuation were also investigated.
MATERIAL AND METHODS
This study followed the 2020 PRISMA guidelines. The literature search started in December 2022 accessing PubMed, Google scholar, Embase, and Scopus databases. All the RCTs investigating the efficacy and safety of daily administration of duloxetine for fibromyalgia were accessed. Studies reporting quantitative data under the outcomes of interest, and including a minimum of 10 patients who completed a minimum of 4 weeks follow-up, were included. Studies on combined pharmacological and non-pharmacological managements for fibromyalgia were not considered.
RESULTS
Data from 3432 patients (11 RCTs) were included. The mean age of the patients was 46.4 ± 10.7 years old, and the mean BMI 25.3 ± 3.2 kg/m. 90% (3089 of 3432 patients) were women. The 60 mg/daily cohort reported the higher FIQ, followed by the 30, 30-60, 120 mg/daily, and placebo groups, while the 60-120 mg /daily group performed the worst results. Concerning the CGI severity scale, placebo resulted in the lowest improvement, and no differences were found in the other groups. Concerning the BPI interference and severity pain scores, the 30-60 mg/daily group reported the worst result, along with the placebo group. The rate of adverse events leading to study discontinuation were lower in the 60-120 group, followed by the 30-60 and 30 mag/daily groups. Duloxetine was superior in all the comparisons to placebo, irrespective of the doses, in all endpoints analysed.
CONCLUSIONS
Duloxetine could help in improving symptoms of fibromyalgia. The dose of duloxetine should be customised according to individual patients. Irrespective of the doses, duloxetine was more effective than placebo in the management of fibromyalgia. The dose of duloxetine must be customised according to individual patients. Level of evidence I Meta-analysis of double-blind RCTs.
Topics: Humans; Female; Adult; Middle Aged; Male; Duloxetine Hydrochloride; Fibromyalgia; Thiophenes; Treatment Outcome; Pain; Randomized Controlled Trials as Topic
PubMed: 37461044
DOI: 10.1186/s13018-023-03995-z -
Journal of Orthopaedic Surgery and... Jul 2023To evaluate the efficacy of duloxetine in the treatment of patients with axial symptoms after posterior cervical spine surgery.
PURPOSE
To evaluate the efficacy of duloxetine in the treatment of patients with axial symptoms after posterior cervical spine surgery.
METHODS
Patients with axial symptoms after posterior cervical spine surgery treated by duloxetine or non-drug therapy from 2018 to 2021 were reviewed. Duloxetine was administered gradually, with oral administration of 30 mg in the first week and oral administration of 60 mg from the second week. Visual analogue scale (VAS), 36-Item Short-Form Health Survey questionnaire (SF-36) and EuroQol-5 Dimensions (EQ-5D) questionnaire were used to evaluate the severity of AS at baseline and 1 week, 2 weeks, 1 month, 3 months and 6 months after medication. The occurrence of adverse reactions was recorded.
RESULTS
A total of 63 eligible patients who received duloxetine therapy (n = 35) or non-drug therapy (n = 28) were included. All patients were followed up for 6 months. Significant improvements were found in VAS score compared with baseline in both groups (1.87 ± 0.81 vs 6.61 ± 1.16, 3.18 ± 0.67 vs 6.31 ± 1.40; P < 0.05 for all). Meanwhile, the VAS score of the duloxetine group was significantly better than that of the non-drug therapy group at 1 week, 2 weeks, 1 month, 3 months and 6 months (P < 0.05). Besides, according to 36-Item Short-Form Health Survey questionnaire (SF-36), the PCS score and MCS score are significantly higher than before the treatment in duloxetine group (PCS 62.82 ± 6.04 vs 44.36 ± 7.25, MCS 65.50 ± 4.53 vs 55.55 ± 6.06; P < 0.05 for all). And when we compared variables between the two groups, the PCS score of the duloxetine group was significantly better than that of the non-drug therapy group (P < 0.05), but there was no significant difference in MCS score between the two groups (P > 0.05). What's more, EQ-5D score had significant improvements in the duloxetine group compared with the non-drug therapy group at 1 week, 2 weeks, 1 month, 3 months and 6 months (P < 0.05).
CONCLUSION
Oral duloxetine has a better short-term outcome than conventional non-drug therapy in patients with axial symptoms following posterior decompression surgery in the cervical spine.
Topics: Humans; Retrospective Studies; Duloxetine Hydrochloride; Treatment Outcome; Administration, Oral; Cervical Vertebrae
PubMed: 37438835
DOI: 10.1186/s13018-023-03970-8 -
International Journal of Pharmaceutics:... Dec 2023Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL...
Formulation, optimization, in-vivo biodistribution studies and histopathological safety assessment of duloxetine HCl-loaded ultra-elastic nanovesicles for antidepressant effect after intranasal and transdermal delivery.
Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL suffers limited bioavailability due to extensive gastric and first-pass metabolism. To improve DUL's bioavailability; DUL-loaded elastosomes were developed, via full factorial design, utilizing various span®60: cholesterol ratios, edge activator types and amounts. Entrapment efficiency (E.E.%), particle size (PS), zeta potential (ZP) and in-vitro released percentages after 0.5 h (Q) and 8 h (Q) were evaluated. Optimum elastosomes (DUL-E1) were assessed for morphology, deformability index, drug crystallinity and stability. DUL pharmacokinetics were evaluated in rats following intranasal and transdermal application of DUL-E1 elastosomal gel. DUL-E1 elastosomes [comprising span®60 and cholesterol (1:1) and brij S2 (edge activator; 5 mg)] were optimum with high E.E.% (81.5 ± 3.2%), small PS (432 ± 13.2 nm), ZP (-30.8 ± 3.3 mV), acceptable Q (15.6 ± 0.9%), and high Q (79.3 ± 3.8%). Intranasal and transdermal DUL-E1 elastosomes revealed significantly higher C (251 ± 18.6 and 248 ± 15.9 ng/mL) at T (2 and 4 h) and improved relative bioavailability (≈ 2.8 and 3.1 folds) respectively, in comparison to oral DUL aqueous solution. In-vivo histopathological studies were conducted to ensure the safety of DUL-E1. Elastosomes are promising novel nano-carriers, capable of enhancing the bioavailability of DUL via various routes of administration.
PubMed: 37434966
DOI: 10.1016/j.ijpx.2023.100194 -
Archives of Gynecology and Obstetrics Sep 2023Stress urinary incontinence (SUI) is defined as urinary incontinence that occurs with coughing, sneezing, and physical exercise. It is frequently observed in women after...
OBJECTIVES
Stress urinary incontinence (SUI) is defined as urinary incontinence that occurs with coughing, sneezing, and physical exercise. It is frequently observed in women after middle age and has a negative impact on their sexual function. Duloxetine as one of the Serotonin-noradrenaline reuptake inhibitors (SNRIs) is commonly used in the non-surgical treatment of SUI. The aim of our study is to investigate the effect of duloxetine, which is used in the treatment of SUI, on sexual functions in female patients.
METHODS
The study included 40 sexually active patients who received duloxetine 40 mg twice a day for the treatment of SUI. All patients had female sexual function index (FSFI), Beck's depression inventory (BDI), and incontinence quality of life score (I-QOL) applied before and 2 months after starting duloxetine treatment.
RESULTS
FSFI total score significantly increased from 19.9 to 25.7 (p < 0.001). In addition, significant improvement was observed in all sub-parameters of FSFI, including arousal, lubrication, orgasm, satisfaction, and pain/discomfort (p < 0.001, for each FSFI subtotal score). BDI significantly decreased from 4.5 to 1.5 (p < 0.001). I-QOL score significantly increased from 57.6 to 92.7 after the duloxetine treatment.
CONCLUSIONS
Although SNRIs carry a high risk of sexual dysfunction, duloxetine may have an indirect positive effect on female sexual activity, both through its stress incontinence treatment and its antidepressant effect. In our study, Duloxetine, one of the treatment options for stress urinary incontinence and an SNRI, has a positive effect on stress urinary incontinence, mental health, and sexual activity in patients with SUI.
Topics: Female; Humans; Middle Aged; Duloxetine Hydrochloride; Norepinephrine; Quality of Life; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Urinary Incontinence, Stress; Sexual Dysfunction, Physiological
PubMed: 37386151
DOI: 10.1007/s00404-023-07123-4 -
Clinical and Experimental Rheumatology Jun 2023Fibromyalgia (FM) is characterised by a form of debilitating pain that is unresponsive to standard analgesics. The aim of this study was to evaluate the efficacy of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Fibromyalgia (FM) is characterised by a form of debilitating pain that is unresponsive to standard analgesics. The aim of this study was to evaluate the efficacy of supplementing ongoing pregabalin (PGB) and duloxetine (DLX) treatment with palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) for 24 weeks in FM patients.
METHODS
After undergoing three months of stable treatment with DLX+PGB, FM patients were randomised to continue the same treatment (Group 1) or to add PEA 600 mg b.i.d + ALC 500 mg b.i.d. (Group 2) for a further 12 weeks. Every two weeks throughout the study, cumulative disease severity was estimated using the Widespread Pain Index (WPI) as the primary outcome measure; the secondary outcomes were the fortnightly scores of the patient-completed revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FASmod) questionnaire. All three measures were expressed as time-integrated area under the curve (AUC) values.
RESULTS
One hundred and thirty (91.5%) of the initial 142 FM patients completed the study: 68 patients in Group 1 and 62 in Group 2. Twenty-four weeks after randomisation, the Group 2 patients showed additional significant improvements in all three outcome measures. Although there was some fluctuation in both groups during the study period, the AUC values of the WPI scores steadily decreased in Group 2 (p=0.048), which also showed better outcomes in terms of the AUC values of the FIQR (p=0.033) and FASmod scores (p=0.017).
CONCLUSIONS
This is the first randomised controlled study demonstrating the effectiveness of the adding on therapy of PEA+ALC to DLX+PGB in FM patients.
Topics: Humans; Fibromyalgia; Duloxetine Hydrochloride; Pregabalin; Acetylcarnitine; Treatment Outcome; Analgesics; Pain
PubMed: 37378482
DOI: 10.55563/clinexprheumatol/pmdzcq -
International Journal of Surgery... Oct 2023
Topics: Humans; Arthroplasty, Replacement, Knee; Duloxetine Hydrochloride; Osteoarthritis, Knee
PubMed: 37352523
DOI: 10.1097/JS9.0000000000000567 -
Drugs Aug 2023Despite being an essential part of whole-person care, patients with cancer often experience complex and under-treated pain. Managing cancer-related pain in patients who... (Review)
Review
Despite being an essential part of whole-person care, patients with cancer often experience complex and under-treated pain. Managing cancer-related pain in patients who are also pregnant compounds the challenge for adequate pain management, as studies have largely excluded this population. Therapy for pain management should be guided by the cause and mechanism of pain. The objective of this review is to provide clinicians with an understanding of pain experienced by pregnant patients with cancer and medications that may be used to help manage cancer-related pain. Nociceptive pain results from damage to somatic or visceral tissues that may be directly caused by cancer. This type of pain can be managed in pregnant patients using acetaminophen and/or nonsteroidal antiinflammatory drugs as first-line agents. In nociceptive pain not managed by non-opioid analgesics, buprenorphine is recommended for those requiring chronic opioids to help manage their pain. Neuropathic pain that results from damage to the peripheral or central nervous system may also be directly caused by cancer, particularly chemotherapy. In pregnant patients, duloxetine and gabapentin should be considered first. Venlafaxine, pregabalin, tricyclic antidepressants, and sodium channel blockers should be avoided, if possible. Nociplastic pain is not directly caused by cancer but may be caused by ongoing peripheral nociceptive input or a condition that predates the cancer diagnosis. Duloxetine and gabapentin are reasonable agents to consider for treatment of nociceptive pain in pregnant patients. Cyclobenzaprine may also be helpful for nociplastic pain.
Topics: Humans; Pregnancy; Female; Gabapentin; Analgesics; Duloxetine Hydrochloride; Cancer Pain; Neuralgia; Analgesics, Opioid; Nociceptive Pain; Neoplasms
PubMed: 37347386
DOI: 10.1007/s40265-023-01906-4