Dose Of Duloxetine Research Articles

Efficacy of antidepressants in the treatment of chronic nonspecific low back pain: a systematic review and meta-analysis.

Aim: This study reassesses the efficacy and safety of antidepressants in treating nonspecific chronic low back pain (NCLBP).Materials & methods: A systematic review was conducted following PRISMA guidelines, including randomized clinical trials (RCTs) from PubMed, Embase, Scopus, LILACS, SciELO and Cochrane CENTRAL, published through August 2024. Studies compared antidepressants with placebo or active comparators. The primary outcomes were pain relief and quality of life. Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42023307516.Results: Nine RCTs involving 1758 patients were analyzed. The antidepressants examined included duloxetine, escitalopram, bupropion, amitriptyline, imipramine and desipramine. Duloxetine 60mg significantly reduced pain (MD=-0.57; 95% CI=-0.78 to -0.36) and improved quality of life compared with placebo, with side effects that were generally tolerable. Notably, higher doses of duloxetine (120mg) were associated with an increase in adverse events. However, other antidepressants like amitriptyline and escitalopram demonstrated only modest or inconsistent effects.Conclusion: Duloxetine at 60mg provides consistent pain relief and improves the quality of life in NCLBP, but higher doses increase adverse events. Escitalopram might offer modest benefits but should be considered a third-line treatment. Other antidepressants, such as amitriptyline, bupropion, imipramine and desipramine, have limited evidence supporting their efficacy and are associated with adverse effects.

Vortioxetine reduces the development of pain‐related behaviour in a knee osteoarthritis model in rats: Involvement of nerve growth factor (NGF) down‐regulation

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

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

BackgroundRestless 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 presentationA 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 conclusionsThis 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.

(070) Assessment the Efficacy of Daily Use of Duloxetine in Treatment of Premature Ejaculation: A Prospective Randomized Placebo-Controlled Cross Over Clinical Trial

Abstract Introduction Premature ejaculation is considered to be the most common male sexual disorder, affecting 5% to 40% of sexually active men. Duloxetine is a serotonin and norepinephrine reuptake inhibitor. •It inhibits the reuptake of serotonin and norepinephrine, combining two therapeutic mechanisms in one agent to treat depression and anxiety and also raises dopamine levels. Objective The aim of this study is evaluating the efficacy of “daily” use of Duloxetine in treatment of PE either primary or secondary. Methods •This Randomized Clinical Trial enrolled among (68) Male patients had Premature ejaculation (PE) diagnosed with quantification of the intra-vaginal ejaculation latency time (IELT) less than 2 minutes. •The (68) potent male patients complaining of PE were divided into two groups: - •Intervention arm Group (A): patients with PE either primary or secondary that received (duloxetine 30mg) daily for 1 month. •Control arm Group (B): patients with PE either primary or secondary that they received placebo treatment daily for 1 month Results A total of 68 patients were eligible for inclusion in the current study, they had a mean age of 38.4 ± 6.1 years, secondary premature ejaculation accounted for 91.2% of the included patients. Baseline IIEF-5 showed a median of 24 (range 22–33), median AIPE was 19 (range 8–30), median IELT 60 sec (range 30–120), median Male SQOL 20 (range 15–33). •All participants had a median AIPE was 26 (range 9–34), median IELT 180 sec (range 30–240), median Male SQOL 43 (range 18–55) after being treated with duloxetine. While median AIPE after placebo was 19 (range 8–30), IELT after placebo 60 seconds (30–160), Male SQOL after placebo was 21 (range 16–33). Conclusions •A daily dose of Duloxetine (30 mg) had an effective role in improving premature ejaculation (PE)severity and quality of life either primary or secondary regarding Disclosure No.

DULOXETINE HYDROCHLORIDE INDUCED PARESTHESIA - A CASE REPORT

A 45-year-old HIV-positive female patient experienced a generalized burning sensation after the administration of one dose of duloxetine 20 mg. The patient’s concurrent medications include a fixed drug combination of nevirapine 200 mg, Lamivudine 150 mg, and Zidovudine 300 mg, twice daily for 5 years. The patient recovered from the generalized burning sensation the next day after the withdrawal of duloxetine. From the causal relationship assessment, we observed that neither the disease, comorbid conditions, nor concurrent medications were found responsible for the burning sensation experience in this patient. Available data from post-marketing surveillance of duloxetine suggest that to date the incidence of duloxetine-induced burning sensation of skin was reported to be 1 in 870 patients. Health-care providers should watch for this rare but important adverse effect of duloxetine.

Baseline depressive symptoms as predictors of efficacy and tolerability of the treatment with duloxetine: a network analysis approach.

Depression is considered one of the most prevalent and burdensome mental disorders. Only 50-60% of patients respond to first-line treatment. Individuals with depression might benefit from personalized treatment, tailored to the individual needs of the patient. In this study, we aimed to explore the baseline characteristics of depressive symptoms associated with a good response to duloxetine treatment using a network analysis. Additionally, the relationship between baseline psychopathological symptoms and treatment tolerability was assessed. The sample of 88 drug-free patients with active depressive episode, who started monotherapy with increasing doses of duloxetine were evaluated. The Hamilton Depression Rating Scale (HAM-D) was used to assess depression severity and the UKU side effect rating scale to monitor adverse drug reactions (ADRs). A network analysis that explored interactions of specific baseline depression symptoms, treatment efficacy and tolerability was performed. The node representing duloxetine treatment efficacy was directly connected to the nodes representing the first HAM-D item ("depressed mood") (edge weight = 0.191) and duloxetine dose (edge weight = 0.144). The node representing ADRs was directly connected to only one node representing the baseline score of the HAM-D anxiety (psychic) item (edge weight = 0.263). Our findings indicate that individuals with depression presenting greater levels of depressed mood and lower levels of anxiety symptoms might better respond to the treatment with duloxetine in terms of efficacy and tolerability.

Discovering interactions in augmentation strategies: Impact of duloxetine on the metabolism of aripiprazole.

We aimed to unravel potential pharmacokinetic interactions between aripiprazole and duloxetine. Plasma concentrations of aripiprazole in two groups of 78 patients each, receiving aripiprazole as a monotherapy or combined with duloxetine, were compared. A potential impact of duloxetine on the metabolism of aripiprazole was expected in higher plasma concentrations of aripiprazole and higher dose-adjusted plasma concentrations. Patients co-medicated with duloxetine showed significantly higher plasma concentrations of aripiprazole by 54.2% (p= 0.019). Dose-adjusted plasma concentrations were 45.6% higher (p= 0.001); 12.8% of these patients exhibited aripiprazole plasma concentrations above the upper limit of the therapeutic reference range, in the control group this was only the case for 10.3% of the patients. A positive relationship was found between the daily dose of duloxetine and dose-adjusted plasma concentrations of aripiprazole (p= 0.034). As dehydroaripiprazole concentrations were not available, conclusions for the active moiety (aripiprazole plus dehydroaripiprazole) could not be drawn. Combining duloxetine and aripiprazole leads to significantly higher drug concentrations of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider increasing aripiprazole concentrations when adding duloxetine to a treatment regimen with aripiprazole.

Application of interpersonal psychotherapy for late-life depression in China: A case report.

Interpersonal psychotherapy (IPT) is an effective treatment for late-life depression, but little is known about its acceptability and efficacy in Chinese patients. This case report describes the use of IPT in a depressed elderly Chinese man. The patient was a 79-year-old widower who lives alone in a large city in China. This was his first contact with a mental health specialist. His wife died one ago, and his only child lives in the United States with her husband and children. Due to the COVID-19 pandemic, his daughter could not visit him, and his usual social interactions decreased, leaving him feeling isolated, lonely, and depressed. He was diagnosed with a major depressive episode and initially prescribed venlafaxine. However, he failed to show an adequate response to medication and the side effects were intolerable. He was switched to a low dose of Duloxetine (60 mg) combined with IPT. The patient's baseline score on the 17-item Hamilton depression rating scale (HAM-D) was 29, suggesting severe levels of depression. He received 12 sessions of IPT. Role transition was the focus of therapy. Although the patient expressed discomfort in therapy, he developed a good rapport with the therapist and was compliant with treatment. Clinical recovery was achieved at the end of acute IPT treatment (HAM-D score = 1). Response to IPT was excellent in this elderly patient, but several points should be noted. First, mental health-related stigma in China can affect treatment engagement. Second, older Chinese are reluctant to speak openly about their personal experiences and feelings. Hence, repeated emphasis on the principles of confidentiality in psychotherapy and forming a strong therapeutic alliance are important. Third, the "empty-nest" household is an emergent phenomenon in China. Helping elderly Chinese navigate changes in traditional Chinese living arrangements and negotiate filial piety with offspring who have moved away are important issues to address in therapy.

Randomized active-controlled study of a single preoperative administration of duloxetine to treat postoperative pain and numbness after posterior lumbar interbody fusion surgery

This prospective, randomized, double-blinded, active controlled trial assessed whether a single preoperative administration of 40 mg of duloxetine could decrease postoperative pain and numbness after posterior lumbar interbody fusion surgery (PLIF). Patients with an American Society of Anesthesiologists physical status I or II undergoing PLIF were included. At 2 hours before inducing anesthesia, patients were administered 40 mg duloxetine or 4 mg diazepam (control drug). Postoperative pain and other symptoms were evaluated on the basis of a visual analog scale, amount of fentanyl used, fentanyl dose request times, rate of use of adjunctive analgesics (diclofenac sodium or pentazocine), and lower limb numbness score (0-3) during the first 2 postoperative days. Forty-six patients were randomly assigned to the duloxetine and diazepam groups (n = 23 each); 6 were lost to follow-up, and analysis was performed on data from 22 patients in the duloxetine group and 18 in the diazepam group. No significant differences were detected in the patient background, postoperative visual analog scale score at rest in the lumbar region and lower limbs, fentanyl use, rate of analgesic adjuvant use, or incidence of side effects. The numbness score in the lower limbs, however, was significantly lower in the duloxetine group. A single preoperative 40-mg dose of duloxetine did not improve postoperative pain after PLIF, but did improve lower limb numbness. Duloxetine may suppress neuropathic pain-like symptoms after PLIF surgery.

Determination of Patient Adherence for Duloxetine in Urine.

Duloxetine, known by its brand name, CymbaltaTM, is a selective serotonin and norepinephrine reuptake inhibitor used to treat major depressive disorders. Determination of patient compliance for duloxetine is typically determined through medication possession ratio (MPR) or plasma concentrations. The purpose of this paper was to characterize normal urinary duloxetine concentrations in patients prescribed duloxetine to monitor patient adherence. Patient data collected from routine screens for duloxetine concentrations in urine were included in this study. Inclusion criteria consisted of patients who were prescribed duloxetine and (i) tested positive for duloxetine, (ii) tested negative for illicit substances and (iii) included creatinine, age and duloxetine dose administered. Of the 5,592 patient urines screened, 2,004 of the results fit into the inclusion criteria. Positive urine concentrations of duloxetine ranged from 50 to 2,722 ng/mL. Duloxetine urine concentrations were normalized to creatinine and dose further characterized by sex, age, body mass index (BMI) and dose in milligrams. Sample distribution included urines collected from 1,487 females and 517 males. The age range of the specimen donors was between 15 and 90 years old with an average age of 52. BMI levels ranged from 13.9 (underweight) to 88.1 (obese), with the average BMI being 33.5. The most common dose of duloxetine prescribed was a daily, oral dose of 60 mg. Analysis of the normalized, transformed creatinine concentrations showed that there was a significant statistical difference (P < 0.05) in the urinary duloxetine concentrations by sex and by dose (mg). Female patients further showed a statistical difference in urinary duloxetine concentration in age groups 18-64 and 64 and older. By characterizing urinary duloxetine concentrations in patients prescribed the medication, normalized distributions of data ranges have been established. These data ranges for urinary duloxetine concentrations can be used to determine patient compliance with duloxetine in routine, clinical samples.

Evaluating the Safety of Electroconvulsive Shock and Duloxetine Combination Therapy on Behavioral, Cardiovascular, and Brain Oxidative Stress Markers in the Mice

Background: Electroconvulsive Therapy (ECT) as a well-established and effective therapeutic approach for the treatment of various psychiatric disorders is an excellent option to treat the major depressive disorder (MDD). The goal of this experimental study was to determine the possible sides effects of electroconvulsive shock (ECS) and duloxetine, a serotonin-norepinephrine Reuptake Inhibitors (SNRIs), and evaluate the safety of this therapeutic approach on behavioral factors, cardiovascular function, and brain oxidative stress markers on mice. Materials and Methods: Animals were divided into different groups receiving either ECS or different doses (10, 20, 40, 80, or 120 mg) of duloxetine alone or together. We evaluated the behavioral factors associated with administration of ECS with or without duloxetine. In addition, we monitored the ECGs (electrocardiogram) of animals prior to and after the experiment and also evaluated the oxidative stress markers including TAC, MDA, and GSH mice’s brains. Results: We did not detect any significant differences in terms of heart rate, RR interval, PR interval, QT, or corrected QT (QTc) between groups that received different doses of duloxetine in combination with ECS compare to the control group. Our findings suggest that while administration of ECS solely increased the oxidative stress markers and decreased the antioxidant capacity of the brain, a combination of duloxetine and ECS at certain doses alleviates the oxidative stress condition and increases the antioxidant capacity of the brain. Conclusion: Overall, this study suggests that the combination of ECS and duloxetine is safe and considerable for further studies on human subjects.

Evaluating the Effect of Electroconvulsive Shock and Duloxetine Combination Therapy on Behavioral, Cardiovascular, and Brain Oxidative Stress Markers in the Rats

Background: Electroconvulsive Therapy (ECT) as a well-established and effective therapeutic approach for the treatment of various psychiatric disorders is an excellent option to treat the major depressive disorder (MDD). The goal of this experimental study was to determine the possible sides effects of electroconvulsive shock (ECS) and duloxetine, a serotonin-norepinephrine Reuptake Inhibitors (SNRIs), and evaluate the safety of this therapeutic approach on behavioral factors, cardiovascular function, and brain oxidative stress markers on mice. Materials and Methods: Animals were divided into different groups receiving either ECS or different doses (10, 20, 40, 80, or 120 mg) of duloxetine alone or together. We evaluated the behavioral factors associated with administration of ECS with or without duloxetine. In addition, we monitored the ECGs (electrocardiogram) of animals prior to and after the experiment and also evaluated the oxidative stress markers including TAC, MDA, and GSH mice’s brains. Results: We did not detect any significant differences in terms of heart rate, RR interval, PR interval, QT, or corrected QT (QTc) between groups that received different doses of duloxetine in combination with ECS compare to the control group. Our findings suggest that while administration of ECS solely increased the oxidative stress markers and decreased the antioxidant capacity of the brain, a combination of duloxetine and ECS at certain doses alleviates the oxidative stress condition and increases the antioxidant capacity of the brain. Conclusion: Overall, this study suggests that the combination of ECS and duloxetine is safe and considerable for further studies on human subjects.

Clinical effects of two different doses of duloxetine compared to conventional analgesic therapy in patients with osteoarthritis knee

Background: Pain is the leading symptom of knee osteoarthritis (OA) leading to significant morbidity and decreased quality of life. Duloxetine, a selective serotonin norepinephrine reuptake inhibitor, has been demonstrated to have a centrally acting analgesic effect. Aims and Objectives: To evaluate the efficacy and safety of two different doses of duloxetine and compare with conventional pharmacotherapy in treatment of chronic pain due to osteoarthritis of knee. Materials and Methods: 90 patients with symptomatic knee OA were randomly divided into 3 groups to receive duloxetine 40 mg &amp; 3g paracetamol/day (Group A), duloxetine 20 mg &amp; 3g paracetamol/day (Group B) and paracetamol 3gm/day (Group C). Patients were followed up for 6 months to assess pain relief and functional improvement. Visual Analogue Scale (VAS) for assessing pain intensity and Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire physical function subscale for assessing physical function were used. Results: Reduction in VAS score from baseline was significantly high in groups A and B as compared to C at 1 month, 3 months and 6 months. Reduction in WOMAC score from baseline were also significantly high in groups A and B as compared to C at 1 month, 3 month and 6 months. Adverse effects in Group A were significantly high as compared to group B and C. Patients discontinuing due to adverse effects were significantly high in group A. Conclusion: Lower dose of duloxetine is associated with significant pain reduction and improved function with lesser adverse effects in patients with pain due to knee OA.

The Efficacy of Preoperative Duloxetine in Patients Undergoing Major Abdominal Cancer Surgery: A Randomized Controlled Trial.

We aimed to evaluate the analgesic efficacy as well as the postoperative quality of recovery of preoperative oral duloxetine a serotonin and norepinephrine reuptake inhibitor for patients undergoing major abdominal cancer surgery. Sixty-two patients, undergoing major abdominal cancer surgery were divided into 2 equal groups, received oral duloxetine 60 mg (2 h preoperative) or placebo. Postoperative 48 hours morphine consumption, visual analog scale pain score, and quality of recovery were measured. The cumulative 48 hours morphine consumption was significantly reduced in the duloxetine group compared with the placebo group (mean±SD) (5.2±3.2 vs. 12.9±3.4 mg), mean difference (95% confidence interval) 7.6 mg (5.9-9.3) P<0.001. The time to first morphine request was delayed significantly in the duloxetine group, median (interquartile range), 25 (19 to 38) versus 8 (4 to 9) hours, P<0.001. The duloxetine group had lower pain scores than the placebo group at 8, 12, 16, and 24 hours postoperatively, however, nonsignificant changes were observed at 0, 2, 4, 36, and 48 hours postoperatively. Participants in the duloxetine group had a better postoperative quality of recovery than the placebo group. The median (interquartile range) of the global quality of recovery-40 scoring system for the duloxetine group was 185 (180 to 191) compared with 170 (163 to 175) in the placebo group (P<0.001). A single preoperative dose of oral duloxetine, 60 mg for patients subjected to major abdominal cancer surgery reduced postoperative pain, decreased opioid consumption, and improved the quality of recovery.

Weight Gain in Veterans Taking Duloxetine, Pregabalin, or Both for the Treatment of Neuropathy.

Peripheral neuropathy is a common condition with an estimated incidence of 3 million cases in the United States per year, with manifestations including weakness, numbness, burning or tingling sensations, and lingering pain. The burden of neuropathy may be greater among veterans due to the higher prevalence of type 2 diabetes mellitus (T2DM) and an aging population. Among the medications used to treat neuropathy are duloxetine and pregabalin. It has been observed at the Sioux Falls Veterans Affairs Health Care System (SFVAHCS) that veterans who are treated for neuropathy with duloxetine, pregabalin, or both, may experience significant weight gain after starting therapy. The purpose of this study was to evaluate the association of weight gain in veterans taking duloxetine, pregabalin, or both, for the treatment of neuropathy. This was a retrospective, chart review study conducted at the SFVAHCS. The primary end point of this study was the change in body weight, expressed in pounds, after 12 to 18 months of treatment. The secondary end points of this study were the percent change in body weight; duration effect; dose effect, which evaluated weight gain at doses of duloxetine > 60 mg/d and pregabalin at doses > 300 mg/d; change in hemoglobin A1c in patients with prediabetes and T2DM, and involvement in the Managing Overweight Veterans Everywhere (MOVE!) weight management program. The change in body weight after 12 to 18 months of treatment was -0.8 lb in the duloxetine group, +2.9 lb in the pregabalin group, and +5.5 lb in the pregabalin plus duloxetine group (P = .12). The change in body weight after > 12 months of treatment was -0.88 lb in the duloxetine group, +3.6 lb in the pregabalin group, and +8.5 lb in the duloxetine plus pregabalin group (P = .046). The change in body weight in patients who received increased doses of the study agents was -2.8 lb in the duloxetine group and +6.5 lb in the pregabalin group (P = .047). There was no significant difference in weight in veterans who took duloxetine, pregabalin, or both, for treatment of neuropathy after 12 to 18 months of therapy. However, there was a difference in weight gain among the 3 groups when therapy lasted > 12 months. The combination therapy of pregabalin and duloxetine was associated with the most amount of weight gain, followed by pregabalin alone. Monotherapy of duloxetine had minimal association with weight gain. In veterans who took increased doses of duloxetine or pregabalin, there was a difference in weight between the monotherapy groups, with pregabalin associated with weight gain and duloxetine associated with weight loss.

Effect of Single Preoperative Dose of Duloxetine on Postoperative Analgesia in Patients Undergoing Total Abdominal Hysterectomy under Spinal Anesthesia.

Background:Women undergoing hysterectomy present a unique set of challenges to the anesthesiologist in terms of postoperative pain management. This study was conducted to see the effect of single-dose perioperative duloxetine 60 mg on postoperative analgesia following abdominal hysterectomy under spinal anesthesia.Materials and Methods:This prospective randomized placebo-controlled study was conducted on 64 patients scheduled to undergo elective abdominal hysterectomy under spinal anesthesia. The patients were divided into two groups of 32 in each, Group D received duloxetine 60 mg 2 h preoperatively and Group P received placebo 2 h preoperatively. Postoperatively, the patients were evaluated by an independent observer for pain on rest and during cough at 0 (arrival at postanesthesia care unit), 2, 4, 6, 12, and 24 h. In addition, the postoperative analgesic requirements and adverse effects were noted.Statistical Analysis Used:Independent t-test/Mann–Whitney U-test was used to compare the pain score between two groups.Results:The demographic data were comparable between both the groups. The mean Visual Analogue Scale scores assessed postoperatively at rest and during cough which were not statistically significant between the two groups. The rescue analgesic consumption in Group D (0.97 ± 0.86) and Group P (1.25 ± 0.76) was comparable and statistically not significant. The total analgesic requirement between duloxetine (4.94 ± 0.84) and placebo (1.25 ± 0.76) group was comparable and statistically not significant. The incidence of nausea vomiting and somnolence was higher in Group D.Conclusion:We conclude that patients receiving a single dose of 60 mg duloxetine as premedication before hysterectomy under spinal anesthesia are no better than placebo on postoperative pain during the first 24 h.

What is the optimal preoperative dose of duloxetine to reduce acute pain in patients undergoing modified radical mastectomy?

What is the optimal preoperative dose of duloxetine to reduce acute pain in patients undergoing modified radical mastectomy?

STATUS CATAPLECTICUS INDUCED BY WITHDRAWAL OF DULOXETINE

SESSION TITLE: Fellows Sleep Disorders Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Status cataplecticus is defined as episodes of cataplexy with an increase in duration and severity of the attacks precipitated by minor or no emotional triggers without a refractory period. It’s a poorly understood rare phenomenon only described in case reports. We are presenting a case of status cataplecticus after the withdrawal of duloxetine CASE PRESENTATION: A 77-year-old female with a history of long-standing narcolepsy with cataplexy stable on methylphenidate 50 mg extended-release a day admitted to hospital for multiple brief periods of whole-body weakness. Patient reported progressively increasing episodes of cataplexy in the last few days with more than ten episodes one day before the presentation which would come on even minor or no emotional stimuli. She was able to recall all the episodes and each episode lasted less than one minute and denied having jerking movements of limbs, incontinence, and or tongue biting. She was also taking duloxetine 60 mg a day for chronic pain due to arthritis for the last one year. She was having issues with dry mouth since being started on duloxetine and stopped taking duloxetine one month before the presentation. Vital signs, physical examination, laboratory workup including CT head was unremarkable. She continued to have these episodes while admitted and were observed by the medical staff. She was started on a lower dose of duloxetine 20 mg twice daily and was observed in the hospital until she stopped having these episodes and discharged back to home without any further recurrence. She was counseled about the negative consequences of the abrupt withdrawal of the medications. DISCUSSION: Cataplexy is defined by REM intrusion into wakefulness clinically apparent as transient muscle weakness brought on by emotional triggers. Most triggers are positive emotions such as laughter, joking and affect the muscles of head and neck with knees and if severe enough can cause paralysis culminating in a fall, however, a typical cataplexy episode is followed by a refractory period of at least a few hours to days in which cataplexy is unlikely to happen again. In status cataplecticus these episodes become very frequent and increase in severity without any significant triggers and lack of refractory period and result in significant debilitation. Most of the cases of status cataplecticus have been described in patients withdrawing from serotonergic adrenergic medications such as SSRI, SNRI, and TCA’s. These medications help decrease REM sleep by increasing the levels of serotonin and norepinephrine and improve cataplexy. Withdrawal can lead to worsening cataplexy symptoms by disinhibiting neurons that promote REM sleep. CONCLUSIONS: Patients of Narcolepsy with Cataplexy should be educated about the possible side effect of withdrawal of SSRI, SNRI and TCA's that can lead to this rare often misdiagnosed phenomenon of status cataplecticus. Reference #1: Wang J, Greenberg H. Status cataplecticus precipitated by abrupt withdrawal of venlafaxine. J Clin Sleep Med. 2013;9(7):715-716. Published 2013 Jul 15. doi:10.5664/jcsm.2848 Reference #2: Martínez-Rodríguez JE, Iranzo A, Santamaría J, et al. Estado de mal catapléjico inducido por la retirada brusca de clomipramina [Status cataplecticus induced by abrupt withdrawal of clomipramine]. Neurologia. 2002;17(2):113-116. DISCLOSURES: no disclosure on file for Humberto Battistini; No relevant relationships by Rose Franco, source=Web Response No relevant relationships by Mohsin Hamid, source=Web Response

Preoperative Duloxetine to improve acute pain and quality of recovery in patients undergoing modified radical mastectomy: A dose-ranging randomized controlled trial

ObjectiveDuloxetine has been recently used as a part of multimodal analgesia in perioperative settings, yet the optimal dose of Duloxetine is not determined. DesignA parallel, randomized, placebo-controlled trial. SettingTertiary level oncology center. Patients88 female patients with breast cancer were subjected to modified radical mastectomy (MRM) with ASA class I and II were recruited. InterventionParticipants were randomly allocated into 4 equal groups received 2 h preoperatively, placebo (D0, N = 22), Duloxetine 30 mg (D30, N = 22), Duloxetine 60 mg (D60, N = 22) and Duloxetine 90 mg (D90, N = 22) tablet. MeasurementsThe primary outcome; 24 h cumulative postoperative morphine consumption and the secondary outcomes; VAS score of pain intensity, quality of recovery (QoR-40), time to Aldrete 9, and side effects (sedation and vomiting) were measured. ResultsThe median (IQR) consumption of morphine (mg) in the first postoperative 24 h was significantly decreased in both (D60 and D90) groups compared to (D0 and D30) groups, P < 0.001(Bonferroni corrected), however, a non-significant reduction was observed between D90 group vs. D60 group and D30 group vs. D0 group, P = 0.595 and P = 0.462 respectively, D60 vs. D0; 0(0–6) vs. 10(9–12), D60 vs. D30; 0(0–6) vs. 9(8–11), D90 vs. D0; 0(0–5) vs. 10(9–12), D90 vs. D30; 0(0–5) vs. 9(8–11), D90 vs. D60; 0(0–5) vs. 0(0–6), D30 vs. D0; 9(8–11) vs. 10(9–12), patients in D90 group took longer time to recover from anesthesia “ time to Aldrete 9” and showed an increased level of sedation in comparison with other groups, vomiting was more frequent in the D90 group. ConclusionPreoperative oral Duloxetine of 60 mg, for patients subjected to MRM is the optimal dose considering its analgesic efficacy and side effects. Trial registrationThe trial was registered at Clinical Trials.gov with unique ID number; NCT03468348.

Assessment of the anti-allodynic efficacy of a glycine transporter 2 inhibitor relative to pregabalin and duloxetine in a rat model of prostate cancer-induced bone pain.

The pathobiology of prostate cancer-induced bone pain (PCIBP) is underpinned by both inflammatory and neuropathic components. Here, we used a rat model of PCIBP to assess the analgesic efficacy of a glycine transporter 2 (GlyT2) inhibitor (N-(6-((1,3-dihydroxypropan-2-yl)amino)-2-(dimethylamino)pyridin-3-yl)-3,5-dimethoxy-4-(4-(trifluoromethyl)phenoxy) benzamide) relative to two clinically available adjuvant drugs that are recommended for the relief of neuropathic pain, viz, pregabalin and duloxetine. PCIBP was induced in male Wistar Han rats following intra-tibial injection (ITI) of rat prostate cancer (AT3B) cells into the left tibia. Sham-rats received an ITI of heat-killed AT3B cells. PCIBP rats with fully developed mechanical allodynia in the ipsilateral hindpaws as assessed using von Frey filaments, received single oral (p.o.) bolus doses of the GlyT2 inhibitor (3-30mg/kg), pregabalin (3-100mg/kg), duloxetine (3-100mg/kg), or vehicle. Baseline paw withdrawal thresholds (PWTs) were determined in the ipsilateral (injured side) and contralateral hindpaws immediately prior to dosing and at scheduled times for 3h post dosing in individual animals. Single oral bolus doses of the GlyT2 inhibitor (3-30mg/kg) evoked partial pain relief at the doses tested in the ipsilateral hindpaws of PCIBP rats without any discernible behavioural side effects. By contrast, single oral bolus doses of pregabalin at 10-100mg/kg evoked dose-dependent and complete alleviation of mechanical allodynia. By comparison, single oral bolus doses of duloxetine at doses up to 100mg/kg lacked efficacy. Oral administration of this GlyT2 inhibitor evoked partial pain relief in PCIBP rats and did not evoke central nervous system side effects in contrast to GlyT2 inhibitors reported by others.