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Clinical Infectious Diseases : An... Apr 2024Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postherpetic neuralgia (PHN) is the most common chronic complication of herpes zoster (HZ) and results in severe refractory neuropathic pain. This study aimed at evaluating the efficacy of premedication with duloxetine in the prevention of PHN.
METHODS
The PROCESS trial is a multicenter, randomized, open-label, blinded-endpoint trial used a 1:1 duloxetine:control ratio. Adults 50 years or older with HZ who presented with vesicles within 72 hours were recruited. The primary outcome was the incidence of PHN at 12 weeks. PHN was defined as any pain intensity score other than 0 mm on the visual analog scale (VAS) at week 12 after the onset of the rash. The secondary outcomes were the number of participants with VAS >0 and VAS ≥3. The modified intention-to-treat (mITT) principle and per-protocol (PP) principle were used for the primary outcome analysis.
RESULTS
A total of 375 participants were randomly assigned to the duloxetine group and 375 were assigned to the control group. There was no significant difference in the incidence of PHN in the duloxetine group compared with the control group in the mITT analysis (86 [22.9%] of 375 vs 108 [28.8%] of 375; P = .067). PP analysis produced similar results. However, there were significant differences between the 2 groups in the number of participants with VAS >0 and VAS ≥3 (P < .05 for all comparisons).
CONCLUSIONS
Although absolute prevention of PHN does not occur, this trial found that premedication with duloxetine can reduce pain associated with HZ, and therefore can have clinically relevant benefits. Clinical Trials Registration. Clinicaltrials.gov, NCT04313335. Registered on 18 March 2020.
Topics: Adult; Humans; Neuralgia, Postherpetic; Duloxetine Hydrochloride; Herpes Zoster; Herpesvirus 3, Human; Pain Measurement
PubMed: 38015658
DOI: 10.1093/cid/ciad714 -
Journal of Oral Rehabilitation Mar 2024Conditioned pain modulation (CPM) is a potential predictor of treatment response that has not been studied in temporomandibular disorders (TMD). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Conditioned pain modulation (CPM) is a potential predictor of treatment response that has not been studied in temporomandibular disorders (TMD).
OBJECTIVES
We conducted a randomised, double-blind, placebo-controlled trial (RCT) of duloxetine in addition to self-management (SM) strategies to investigate its efficacy to reduce pain intensity in painful TMD patients. Moreover, we investigated whether baseline CPM would predict the duloxetine efficacy to reduce TMD pain intensity.
METHODS
Eighty participants were randomised to duloxetine 60 mg or placebo for 12 weeks. The primary outcomes were the change in the pain intensity from baseline to week-12 and CPM-sequential paradigm at baseline. Safety, physical and emotional functioning outcomes were also evaluated.
RESULTS
Of 80 participants randomised, 78 were included in intention-to-treat analysis. Pain intensity decreased for SM-duloxetine and SM-placebo but did not differ between groups (p = .82). A more efficient CPM was associated with a greater pain intensity reduction regardless of the treatment group (p = .035). Physical and emotional functioning did not differ between groups, but adverse events (p = .014), sleep impairment (p = .003) and catastrophizing symptoms (p = .001) were more prevalent in SM-duloxetine group.
CONCLUSION
This study failed to provide evidence of a beneficial effect of adding duloxetine to SM strategies for treatment of painful TMD. Nonetheless, this RCT has shown the feasibility of applying pain modulation assessment to predict short-term treatment response in painful TMD patients, which confirms previous finds that CPM evaluation may serve a step forward in individualising pain treatment.
Topics: Humans; Double-Blind Method; Duloxetine Hydrochloride; Pain; Self-Management; Temporomandibular Joint Disorders; Treatment Outcome
PubMed: 37994185
DOI: 10.1111/joor.13628 -
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 -
International Journal of Clinical... Feb 2024A 70-year-old male taking venlafaxine for depression developed interstitial pneumonia and was admitted with shortness of breath and dyspnea. A computed tomography (CT)...
A 70-year-old male taking venlafaxine for depression developed interstitial pneumonia and was admitted with shortness of breath and dyspnea. A computed tomography (CT) chest scan showed diffuse multiple lung lesions in both lungs, suggesting interstitial changes with inflammation or exudation. Compared with the CT chest scan 1 month earlier, there were significant progresses and new findings. The clinical diagnosis was interstitial pneumonia with pulmonary infection. The patient had been treated with fluvoxamine 100 mg/day, duloxetine 60 mg/day, venlafaxine 75 mg/day for depression over the past 4 months. The exacerbation of interstitial pneumonia was suspected to be related to venlafaxine. Wheezing improved slightly after discontinuation of venlafaxine and treatment in the respiratory ICU. However, the patient could not tolerate the ICU environment, therefore became agitated, irritable, and anxious. Finally the patient gave up treatment and was discharged. Three months after discharge, the patient died of a sudden of interstitial pneumonia. A Naranjo assessment score of 3 was obtained, indicating a possible correlation between the patient's adverse drug reaction and the suspect drug.
Topics: Male; Humans; Aged; Venlafaxine Hydrochloride; Lung Diseases, Interstitial; Lung; Duloxetine Hydrochloride; Tomography, X-Ray Computed
PubMed: 37969093
DOI: 10.5414/CP204459 -
BMJ Case Reports Nov 2023A patient in his 60s was admitted for an extensive neurological work-up due to progressive asymmetrical, distally pronounced pain in both feet and legs. Conventional...
A patient in his 60s was admitted for an extensive neurological work-up due to progressive asymmetrical, distally pronounced pain in both feet and legs. Conventional pain relievers did not help in pain reduction. A Sudoscan revealed small fibre damage in all extremities indicating an underlying neuropathy. The patient had started insulin treatment around 6 months prior to hospitalisation because of a newly diagnosed late-onset diabetes. Due to a rapid drop in glycated haemoglobin (from over 14% to 6% in 4 months), treatment-induced neuropathy of diabetes (TIND) was hypothesised. On increasing the dose of pregabalin and adding duloxetine, the patient reported improvement of symptoms, which further underlined the suspected diagnosis. Hence, in patients with severe hyperglycaemia, changes in glycaemic control should be stepwise and not rapid; however, to date, no guidelines exist how to avoid TIND.
Topics: Humans; Diabetic Neuropathies; Neuralgia; Duloxetine Hydrochloride; Analgesics; Diabetes Mellitus, Type 2
PubMed: 37967926
DOI: 10.1136/bcr-2023-256340 -
Biomedicine & Pharmacotherapy =... Dec 2023Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be...
BACKGROUND
Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be elucidated whether these associations are related to exposure to antidepressants, a consequence of a disease process, or a combination of both.
METHODS
This study investigates the independent effect of the antidepressant duloxetine hydrochloride (DH) on ovariectomy-induced bone loss in mice. One week after ovariectomy, the treated mice received DH. To explore the mechanism underlying the rescue of bone loss, bone marrow cells were isolated from mouse femurs and tibias, and macrophages extracted from them were induced to become osteoclasts in vitro while being treated with DH. Subsequently, the osteoclasts underwent Bulk RNA-Seq to reveal the involved signaling pathways. The results of the bioinformatic analysis were then validated through in vitro experiments.
RESULTS
The in vivo experiments demonstrated that DH treatment compromised ovariectomy-induced bone loss after 7 weeks. The in vitro experiments suggested that DH treatment attenuated osteoclast differentiation via the MAPKs/NFATc1 signaling pathway.
CONCLUSION
The findings from this study suggest that DH, instead of causing bone mass loss, may assist in alleviating postmenopausal osteoporosis. These results can serve as a reference for the clinical treatment of patients with perimenopausal or postmenopausal depression using antidepressants.
Topics: Humans; Female; Animals; Mice; Osteoclasts; Duloxetine Hydrochloride; Depressive Disorder, Major; Cell Differentiation; Antidepressive Agents; Ovariectomy; Osteogenesis; RANK Ligand
PubMed: 37913736
DOI: 10.1016/j.biopha.2023.115810 -
The Prostate Feb 2024Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Urinary incontinence (UI) can negatively impact quality of life (QoL) after robot-assisted radical prostatectomy (RARP). Pelvic floor muscle training (PFMT) and duloxetine are used to manage post-RARP UI, but their efficacy remains uncertain. We aimed to investigate the efficacy of PFMT and duloxetine in promoting urinary continence recovery (UCR) after RARP.
METHODS
A randomized controlled trial involving patients with urine leakage after RARP from May 2015 to February 2018. Patients were randomized into 1 of 4 arms: (1) PFMT-biofeedback, (2) duloxetine, (3) combined PFMT-biofeedback and duloxetine, (4) control arm. PFMT consisted of pelvic muscle exercises conducted with electromyographic feedback weekly, for 3 months. Oral duloxetine was administered at bedtime for 3 months. The primary outcome was prevalence of continence at 6 months, defined as using ≤1 security pad. Urinary symptoms and QoL were assessed by using a visual analogue scale, and validated questionnaires.
RESULTS
From the 240 patients included in the trial, 89% of patients completed 1 year of follow-up. Treatment compliance was observed in 88% (92/105) of patients receiving duloxetine, and in 97% (104/107) of patients scheduled to PFMT-biofeedback sessions. In the control group 96% of patients had achieved continence at 6 months, compared with 90% (p = 0.3) in the PMFT-biofeedback, 73% (p = 0.008) in the duloxetine, and 69% (p = 0.003) in the combined treatment arm. At 6 months, QoL was classified as uncomfortable or worse in 17% of patients in the control group, compared with 44% (p = 0.01), 45% (p = 0.008), and 34% (p = 0.07), respectively. Complete preservation of neurovascular bundles (NVB) (OR: 2.95; p = 0.048) was the only perioperative intervention found to improve early UCR.
CONCLUSIONS
PFMT-biofeedback and duloxetine demonstrated limited impact in improving UCR after RP. Diligent NVB preservation, along with preoperative patient and disease characteristics, are the primary determinants for early UCR.
Topics: Male; Humans; Quality of Life; Duloxetine Hydrochloride; Pelvic Floor; Treatment Outcome; Urinary Incontinence; Prostatectomy
PubMed: 37904330
DOI: 10.1002/pros.24634 -
Biological Research For Nursing Apr 2024Development of painful oxaliplatin-induced peripheral neuropathy (OIPN) is a major problem in people who receive oxaliplatin as part of cancer treatment. The pain...
Development of painful oxaliplatin-induced peripheral neuropathy (OIPN) is a major problem in people who receive oxaliplatin as part of cancer treatment. The pain experienced by those with OIPN can be seriously debilitating and lead to discontinuation of an otherwise successful treatment. Duloxetine is currently the only recommended treatment for established painful OIPN recommended by the American Society of Clinical Oncology, but its preventative ability is still not clear. This study examined the ability of duloxetine to prevent signs of chronic OIPN in female (n = 12) and male (n = 21) rats treated with the chemotherapeutic agent oxaliplatin. Using an established model of OIPN, rats were started on duloxetine (15 mg) one week prior to oxaliplatin administration and continued duloxetine for 32 days. Behavioral testing for mechanical allodynia and mechanical hyperalgesia was done with selected von Frey filaments. Significant posttreatment differences were found for allodynia in female ( = .004), but not male rats. Duloxetine was associated with significant differences for hyperalgesia in both female ( < .001) and male ( < .001) rats. These findings provide preliminary evidence of the preventative effects of duloxetine on both oxaliplatin-induced allodynia and hyperalgesia in male and female rats, with a difference noted in response between the sexes.
Topics: Humans; Rats; Male; Female; Animals; Oxaliplatin; Hyperalgesia; Antineoplastic Agents; Duloxetine Hydrochloride; Rats, Sprague-Dawley; Pain; Peripheral Nervous System Diseases
PubMed: 37902612
DOI: 10.1177/10998004231209444 -
European Journal of Pharmaceutical... Jan 2024This study aimed to develop a dissolution test that can predict the bioequivalence (BE) of enteric-coated pellet formulations. The original duloxetine hydrochloride...
This study aimed to develop a dissolution test that can predict the bioequivalence (BE) of enteric-coated pellet formulations. The original duloxetine hydrochloride capsule (reference formulation (RF); Cymbalta® 30 mg capsule) and four generic test formulations (two capsules (CP) and two orally disintegrating tablets (OD)) were used as model formulations. Clinical BE studies were conducted on 24-47 healthy male subjects under fasting conditions. Dissolution tests were performed using a compendial paddle method (PD) (paddle speed: 50 rpm) and a flow-through cell method (FTC) (flow rate: 4 mL/min). For a further test, cotton balls were added to the vessel to apply gentle mechanistic stress to the formulations, and paddle speed was reduced to 10 rpm (paddle with cotton ball method (PDCB)).All the dissolution tests were conducted with 0.01 M HCl (pH 2.0) for 0.5 h followed by 10 mM bicarbonate buffer solutions (pH 6.5) for 4 h. One each of the two CP and two OD showed BE with RF. PDCB was able to discriminate between BE and non-BE formulations, while this was not possible with PD and FTC. In PDCB, the cotton balls intermittently moved the pellets near the vessel bottom. PDCB is useful for predicting BE during formulation development.
Topics: Male; Humans; Bicarbonates; Therapeutic Equivalency; Tablets, Enteric-Coated; Tablets; Duloxetine Hydrochloride; Solubility
PubMed: 37884100
DOI: 10.1016/j.ejps.2023.106622 -
Internal Medicine Journal Apr 2024Fibromyalgia is a common condition characterised by chronic widespread musculoskeletal pain and central sensitivity features. Appropriate management requires a...
BACKGROUND
Fibromyalgia is a common condition characterised by chronic widespread musculoskeletal pain and central sensitivity features. Appropriate management requires a multidisciplinary approach prioritising non-pharmacological strategies. Evidence-based fibromyalgia medications are not always easily available, effective or tolerated.
AIM
To characterise actual medication usage in Australian fibromyalgia patients.
METHODS
Demographic and clinical data, including medication use information, were gathered by chart review from patients attending the Monash Fibromyalgia Clinic between January 2019 and June 2022. Eligible patients were invited to complete an anonymous questionnaire between June and August 2022 to assess current therapeutic use. The questionnaire assessed fibromyalgia clinical features by using the Revised Fibromyalgia Impact Questionnaire and the 2016 modified American College of Rheumatology Fibromyalgia criteria.
RESULTS
The chart review included 474 patients, and 108 participants completed the questionnaire. Most chart review (78.7%) and questionnaire participants (85.2%) reported using at least one medication for their fibromyalgia. 48.5% of chart review patients and 58.3% of questionnaire participants reported using at least one evidence-based medication, usually amitriptyline, duloxetine or pregabalin. However, the most common individual medications for questionnaire participants were non-steroidal anti-inflammatory drugs (48.2%), paracetamol (59.3%) and opioids (34.3%), with most opioids being typical opioids. Among questionnaire participants, 14.8% reported using cannabinoids, and 70.4% reported using at least one supplement, vitamin or herbal/naturopathic preparation. Not all medication or substance use was recorded during clinic appointments.
CONCLUSION
Fibromyalgia patients engage in various pharmacotherapeutic strategies that are not always evidence-based or disclosed to their treating clinicians.
Topics: Humans; United States; Fibromyalgia; Australia; Pregabalin; Duloxetine Hydrochloride; Amitriptyline; Chronic Pain
PubMed: 37872879
DOI: 10.1111/imj.16257