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International Journal of Molecular... Aug 2023Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence...
Depression is a global mental health concern, and personalized treatment approaches are needed to optimize its management. This study aimed to investigate the influence of the CYP2D6 and CYP1A2 gene polymorphisms on the efficacy of duloxetine in reducing depressive and anxiety symptoms. A sample of 100 outpatients with major depression, who initiated monotherapy with duloxetine, were followed up. Polymorphisms in the CYP2D6 and CYP1A2 genes were assessed. The severity of depressive and anxiety symptoms was recorded using standardized scales. Adverse drug reactions (ADRs) were analyzed. Statistical analyses, including linear regression, were conducted to examine the relationships between genetic polymorphisms, clinical variables, and treatment outcomes. Patients with higher values of the duloxetine metabolic index (DMI) for CYP2D6, indicating a faster metabolism, achieved a greater reduction in anxiety symptoms. The occurrence of ADRs was associated with a lower reduction in anxiety symptoms. However, no significant associations were found between studied gene polymorphisms and reduction in depressive symptoms. No significant effects of the DMI for CYP1A2 were found. Patients with a slower metabolism may experience less benefit from duloxetine therapy in terms of anxiety symptom reduction. Personalizing treatment based on the CYP2D6 and CYP1A2 gene polymorphisms can enhance the effectiveness of antidepressant therapy and improve patient outcomes.
Topics: Humans; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Cytochrome P-450 CYP1A2; Duloxetine Hydrochloride; Depression; Drug-Related Side Effects and Adverse Reactions; Polymorphism, Genetic
PubMed: 37686266
DOI: 10.3390/ijms241713459 -
Contemporary Clinical Trials Jun 2024Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can...
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.
Topics: Adult; Female; Humans; Male; Middle Aged; Antidepressive Agents; Anxiety; Combined Modality Therapy; Depression; Duloxetine Hydrochloride; Patient Education as Topic; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38604496
DOI: 10.1016/j.cct.2024.107524 -
BMJ Open Dec 2023Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
Adverse drug events associated with nortriptyline compared with paroxetine and alternative medications in an older adult population: a retrospective cohort study in Southern California.
OBJECTIVE
Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
DESIGN
Retrospective cohort study.
SETTING
The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California.
PARTICIPANTS
Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018.
MAIN OUTCOME MEASURES
HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities.
RESULTS
Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin.
CONCLUSIONS
Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.
Topics: Humans; Aged; Paroxetine; Nortriptyline; Citalopram; Fluoxetine; Sertraline; Venlafaxine Hydrochloride; Amitriptyline; Duloxetine Hydrochloride; Retrospective Studies; Escitalopram; Gabapentin; Drug-Related Side Effects and Adverse Reactions; Syncope
PubMed: 38154883
DOI: 10.1136/bmjopen-2023-076028 -
Pain Physician Jan 2024Knee osteoarthritis (OA) is a common form of arthritis in elders which can lead to reduced daily activity and quality of life. It is important to administer a proper... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Knee osteoarthritis (OA) is a common form of arthritis in elders which can lead to reduced daily activity and quality of life. It is important to administer a proper treatment with high efficacy and low side effects. In this study, we evaluated the efficacy of co-treatment with oral duloxetine and intraarticular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) in patients with knee OA.
OBJECTIVES
This study aimed to test the hypothesis that an IA injection of CS+HA combined with duloxetine could achieve pain management superior to that of an IA injection of CS+HA alone in patients experiencing knee OA related pain.
STUDY DESIGN
This study adopted a prospective, randomized, open-label blind endpoint study design.
SETTING
The investigation was performed at Beijing Tiantan Hospital Affiliated with the Capital Medical University from October 2019 to December 2021. The study plan was approved by the Ethics Committee of Beijing Tiantan Hospital (KY 2019-086-02).
METHODS
A total of 150 patients were randomly allocated to receive either duloxetine combined with an IA injection (n = 75) or a single IA injection alone (n = 75). All patients were followed for 24 weeks. The primary outcome was the change in the weekly 24 hours average mean pain scores, and the secondary outcomes included the proportion of patients with >= 30% or >= 50% pain reduction, Brief Pain Inventory (BPI) items, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Patient Global Impression Improvement (PGI-I) ratings, hospital anxiety and depression scale (HADS) scores and adverse events (AEs)..
RESULTS
Patients in the experimental group had significantly greater improvement in the change of weekly mean of the 24 hours average pain scores, BPI pain severity ratings (P < 0.001) and WOMAC scores (P < 0.001) at the study endpoint. A significantly greater percentage of patients in the experimental group rated PGI-I of <= 2 (P = 0.021) and >= 50% pain reduction (P = 0.029) at 24 weeks. There was no difference in the proportion of patients with <= 30% pain reduction, the HADS scores or frequency of AEs between the 2 groups.
LIMITATIONS
The effectiveness and safety were examined only up to 24 weeks after treatment, and we did not perform a long-term follow-up as most previous studies have. Optimum dosage of duloxetine, as well as different molecular-weight HA, should be investigated in future studies.
CONCLUSION
Patients receiving co-treatment with oral duloxetine and IA (HA+CS) injections experienced considerable improvement in pain and knee function compared to those who received an IA injection alone.
Topics: Humans; Aged; Hyaluronic Acid; Duloxetine Hydrochloride; Osteoarthritis, Knee; Prospective Studies; Quality of Life; Injections, Intra-Articular; Pain; Adrenal Cortex Hormones
PubMed: 38285030
DOI: No ID Found -
BMC Psychiatry Jun 2024Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a...
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.
Topics: Humans; Duloxetine Hydrochloride; Depressive Disorder, Major; Female; Male; Cytokines; Adult; Middle Aged; Antidepressive Agents; Case-Control Studies; Inflammation
PubMed: 38877455
DOI: 10.1186/s12888-024-05910-0 -
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 -
The Primary Care Companion For CNS... Jan 2024
Topics: Humans; Duloxetine Hydrochloride; Hallucinations
PubMed: 38277643
DOI: 10.4088/PCC.23cr03595 -
PloS One 2023The pain subscales of the Knee and Hip Osteoarthritis Outcome Scores (KOOS and HOOS) are among the most frequently applied, patient reported outcomes to assess pain in...
Responsiveness and interpretability of the pain subscale of the Knee and Hip Osteoarthritis Outcome Scale (KOOS and HOOS) in osteoarthritis patients according to COSMIN guidelines.
BACKGROUND
The pain subscales of the Knee and Hip Osteoarthritis Outcome Scores (KOOS and HOOS) are among the most frequently applied, patient reported outcomes to assess pain in osteoarthritis patients and evaluation of the results after Total Knee Arthroplasty (TKA) and Total Hip Arthroplasty (THA). For the evaluation of change over time it is essential to know the responsiveness and interpretability of these measurement instruments. Aim of this study is to investigate responsiveness and interpretability of the KOOS and HOOS pain subscales in patients with knee or hip OA and patients after TKA and THA as recommended by COSMIN guidelines. COSMIN stands for COnsensus based Standards for the selection of health Measurement Instruments. COSMIN recommends methods for assessing responsiveness similar to those assessing validity, using extensive hypothesis testing to assess criterion validity and construct validity of the change score.
DESIGN
This clinimetric study was conducted using data obtained from the Duloxetine in OsteoArthritis (DOA) trial. Primary knee or hip osteoarthritis patients were included. During the study, half of the participants received pre-operative targeted treatment with duloxetine, and all participants received TKA or THA. Patients filled out a set of patient-reported outcomes at several time points.
METHODS
Using the criterion validity approach the change scores of the KOOS and HOOS pain subscales directly after duloxetine treatment but before TKA and THA were correlated to the Patient Global Improvement anchor-question (PGI-I). Receiver Operating Characteristic curves (ROC curves) were obtained. Using the construct validity approach, hypothesis testing was conducted investigating the correlation between change scores in the KOOS and HOOS pain subscale with change scores in other questionnaires six months after TKA and THA. For interpretability, an anchor-based approach was used to consider the Minimally Important Change (MIC) of the KOOS and HOOS pain subscale. We compared the outcomes after duloxetine treatment and six months after TKA and THA in order to investigate any response shift.
RESULTS
Ninety-three participants (53 knee patients and 41 hip patients) were included. Mean change was 4.3 and 4.6 points after conservative treatment for knee and hip OA patients respectively and 31.7 and 48.8 points after TKA and THA respectively. The KOOS and HOOS pain subscales both showed a gradual increase in change scores over the different categories of improvement on the PGI-I, with an Area Under the Curve of 0.72 (95% CI 0.527-0.921) and 0.79 (95% CI 0.588-0.983) respectively. Of the predefined hypotheses, 69% were confirmed for both subscales. The MICs were between 12.2 to 37.9 for the KOOS pain subscale, and between 11.8 to 48.6 for the HOOS pain subscale, depending on whether the PGI-I was administered after conservative treatment, or six months after TKA and THA.
CONCLUSIONS
This study endorses the responsiveness of the KOOS and HOOS pain subscales in patients with knee or hip OA and patients after TKA and THA based on construct and criterion validity approaches. The KOOS pain subscale might be able to detect the MIC at an individual level after arthroplasty, but both the KOOS and HOOS pain subscales were not able to do so after conservative treatment. This study is the first to report a considerable response shift in MIC of the KOOS and HOOS pain subscales. This should be taken into consideration when evaluating MIC of the KOOS and HOOS pain subscale after conservative versus operative treatment. Future research should present more reference data regarding MIC scores after different treatments.
Topics: Humans; Osteoarthritis, Hip; Duloxetine Hydrochloride; Knee Joint; Osteoarthritis, Knee; Pain; Arthroplasty, Replacement, Hip
PubMed: 37971978
DOI: 10.1371/journal.pone.0293760 -
BMC Psychiatry May 2024Restless 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...
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.
Topics: Aged; Female; Humans; Antidepressive Agents; Duloxetine Hydrochloride; Phenotype; Pramipexole; Restless Legs Syndrome; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 38730422
DOI: 10.1186/s12888-024-05763-7 -
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