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Michael J Detke - One of the best experts on this subject based on the ideXlab platform.
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effects of Duloxetine on norepinephrine and serotonin transporter activity in healthy subjects
Journal of Clinical Psychopharmacology, 2014Co-Authors: Jill Chappell, Mary Pat Knadler, Graeme Eisenhofer, Michael J Owens, Harry Haber, Richard D Lachno, Robert A Dean, Charles B Nemeroff, Malcolm I Mitchell, Michael J DetkeAbstract:Duloxetine selectively inhibits the serotonin (5-HT) and norepinephrine (NE) transporters (5-HTT and NET, respectively), as demonstrated in vitro and in preclinical studies; however, transporter inhibition has not been fully assessed in vivo at the approved dose of 60 mg/d. Here, the in vivo effects of dosing with Duloxetine 60 mg once daily for 11 days in healthy subjects were assessed in 2 studies: (1) centrally (n = 11), by measuring concentrations of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylglycol (DHPG), and NE in cerebrospinal fluid, and (2) versus escitalopram 20 mg/d (n = 32) in a 2-period crossover study by assessing the ΔDHPG/ΔNE ratio in plasma during orthostatic testing and by pharmacokinetic/pharmacodynamic modeling of reuptake inhibition using subjects' serum in cell lines expressing cloned human 5-HTT or NET. At steady state, Duloxetine significantly reduced concentrations of DHPG and 5-hydroxyindoleacetic acid (P < 0.05), but not NE, in cerebrospinal fluid; DHPG was also decreased in plasma and urine. The ΔDHPG/ΔNE ratio in plasma decreased significantly more with Duloxetine than escitalopram (65% and 21%, respectively; P < 0.0001). Ex vivo reuptake inhibition of 5-HTT was comparable (EC50 = 44.5 nM) for Duloxetine and escitalopram, but Duloxetine inhibited NET more potently (EC50 = 116 nM and 1044 nM, respectively). Maximal predicted reuptake inhibition for 5-HTT was 84% for Duloxetine and 80% for escitalopram, and that for NET was 67% and 14%, respectively. In summary, Duloxetine significantly affected 5-HT and NE turnover in the central nervous system and periphery; these effects presumably occurred via inhibition of reuptake by the 5-HTT and NET, as indicated by effects on functional reuptake inhibition ex vivo.
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sexual function during long term Duloxetine treatment in patients with recurrent major depressive disorder
The Journal of Sexual Medicine, 2011Co-Authors: Angelluis Montejo, Michael J Detke, Fujun Wang, David G S Perahia, Melissa E Spann, Daniel J Walker, Charles R YangAbstract:ABSTRACT Introduction Sexual dysfunction (SD) is frequently associated with major depressive disorder (MDD) in the untreated state and may be worsened by antidepressant treatment. Aim We evaluated SD in Duloxetine‐treated patients during an MDD recurrence prevention study. Methods Patients (N = 514) received open‐label Duloxetine 60–120 mg/day for up to 34 weeks. Responders (N = 288) were randomly assigned to Duloxetine or placebo during a further 52‐week double‐blind maintenance phase. Main Outcome Measures The Arizona Sexual Experience Scale (ASEX) was used to assess sexual functioning. Results At study entry, 73.4% of patients met ASEX criteria for SD. After open‐label Duloxetine treatment, the probability of continued SD was 77.9% for nonresponders and 53.2% for responders. In patients without SD at study entry, the probability of emergent SD was 49.6% (nonresponders) and 33.2% (responders). In the double‐blind maintenance phase, there was no significant difference ( P = 0.105) in the probability of emergent SD between placebo‐treated (49.2%) and Duloxetine‐treated (27.9%) patients without SD at baseline, with no significant treatment‐by‐gender interaction. In patients with a recurrence of MDD, the probability of emergent SD was similar between placebo‐ (71.3%) and Duloxetine‐treated (82.7%) patients. However, in patients with no recurrence of MDD, the probability of emergent SD in placebo patients (40.0%) was numerically higher than in Duloxetine patients (12.9%). Spontaneous reports of adverse events related to sexual function were infrequent and no patients discontinued due to these events. Conclusions In patients with MDD, the probability of continued or emergent SD after up to 34 weeks of open‐label Duloxetine treatment was associated with the response status of the patients. In patients who responded to Duloxetine treatment, after up to a further 52 weeks of double‐blind treatment either with Duloxetine or placebo, the probability of continued or emergent SD appeared to be more related to MDD itself than the treatments that the patients received. Montejo A‐L, Perahia DGS, Spann ME, Wang F, Walker DJ, Yang CR, and Detke MJ. Sexual function during long‐term Duloxetine treatment in patients with recurrent major depressive disorder.
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efficacy and safety of Duloxetine in patients with chronic low back pain
Spine, 2010Co-Authors: Vladimir Skljarevski, Michael J Detke, Smriti Iyengar, H Liuseifert, Qi Zhang, Durisala Desaiah, Amy S Chappell, J H Atkinson, M BackonjaAbstract:STUDY DESIGN This was a randomized, double-blind, placebo-controlled clinical trial. OBJECTIVE To assess the efficacy and safety of Duloxetine in the treatment of chronic low back pain (CLBP). SUMMARY OF BACKGROUND DATA Imbalance of serotonin and norepinephrine within modulatory pain pathways has been implicated in the development and maintenance of chronic pain. Duloxetine, a selective reuptake inhibitor of serotonin and norepinephrine, has demonstrated clinical efficacy in 3 distinct chronic pain conditions: diabetic peripheral neuropathic pain, fibromyalgia, and chronic pain because of osteoarthritis. METHODS In this randomized double-blind trial, adult nondepressed patients with a non-neuropathic CLBP and a weekly mean of the 24-hour average pain score>or=4 at baseline (0-10 scale) were treated with either Duloxetine or placebo for 13 weeks. The dose of Duloxetine during first 7 weeks was 60 mg once daily. At week 7, patients reporting<30% pain reduction had their dose increased to 120 mg. The primary outcome measure was the Brief Pain Inventory (BPI) 24-hour average pain rating. Secondary measures included Roland-Morris Disability Questionnaire-24; Patient's Global Impressions of Improvement; Clinical Global Impressions-Severity (CGI-S); BPI-Severity and -Interference (BPI-I); and weekly means of the 24-hour average pain, night pain, and worst pain scores from patient diaries. Quality-of-life, safety, and tolerability outcomes were also assessed. RESULTS Compared with placebo-treated patients (least-squares mean change of -1.50), patients on Duloxetine (least-squares mean change of -2.32) had a significantly greater reduction in the BPI 24-hour average pain from baseline to endpoint (P=0.004 at week 13). Additionally, the Duloxetine group significantly improved on Patient's Global Impressions of Improvement; Roland-Morris Disability Questionnaire-24; BPI-Severity and average BPI-Interference; weekly mean of the 24-hour average pain, night pain, and worst pain. Significantly more patients in the Duloxetine group (13.9%) compared with placebo (5.8%) discontinued because of adverse events (P=0.047). The most common treatment-emergent adverse events in the Duloxetine group included nausea, dry mouth, fatigue, diarrhea, hyperhidrosis, dizziness, and constipation. CONCLUSION Duloxetine significantly reduced pain and improved functioning in patients with CLBP. The safety and tolerability were similar to those reported in earlier studies.
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Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder a double blind placebo controlled trial
European Neuropsychopharmacology, 2008Co-Authors: Jonathan R T Davidson, Michael J Detke, J Erickson, Susan Ball, Hansulrich Wittchen, Pierremichel Llorca, James M RussellAbstract:The objective was to examine Duloxetine 60-120 mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with Duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (>or=50% reduction in Hamilton Anxiety Rating Scale total score to or=2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than Duloxetine-treated patients (13.7%, N=204, P
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Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder a double blind placebo controlled trial
European Neuropsychopharmacology, 2008Co-Authors: Jonathan R T Davidson, Michael J Detke, J Erickson, Susan Ball, Hansulrich Wittchen, Pierremichel Llorca, James M RussellAbstract:Abstract The objective was to examine Duloxetine 60–120 mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients ( N = 887; mean age = 43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with Duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (≥ 50% reduction in Hamilton Anxiety Rating Scale total score to ≤ 11 and “much”/“very much improved” ratings for the last 2 visits of open-label phase) were randomly assigned to receive Duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as ≥ 2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients ( N = 201) relapsed more frequently (41.8%) than Duloxetine-treated patients (13.7%, N = 204, P ≤ 0.001) and worsened on each outcome measure ( P ≤ 0.001, all comparisons). Duloxetine 60–120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.
Smriti Iyengar - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Duloxetine in patients with chronic low back pain
Spine, 2010Co-Authors: Vladimir Skljarevski, Michael J Detke, Smriti Iyengar, H Liuseifert, Qi Zhang, Durisala Desaiah, Amy S Chappell, J H Atkinson, M BackonjaAbstract:STUDY DESIGN This was a randomized, double-blind, placebo-controlled clinical trial. OBJECTIVE To assess the efficacy and safety of Duloxetine in the treatment of chronic low back pain (CLBP). SUMMARY OF BACKGROUND DATA Imbalance of serotonin and norepinephrine within modulatory pain pathways has been implicated in the development and maintenance of chronic pain. Duloxetine, a selective reuptake inhibitor of serotonin and norepinephrine, has demonstrated clinical efficacy in 3 distinct chronic pain conditions: diabetic peripheral neuropathic pain, fibromyalgia, and chronic pain because of osteoarthritis. METHODS In this randomized double-blind trial, adult nondepressed patients with a non-neuropathic CLBP and a weekly mean of the 24-hour average pain score>or=4 at baseline (0-10 scale) were treated with either Duloxetine or placebo for 13 weeks. The dose of Duloxetine during first 7 weeks was 60 mg once daily. At week 7, patients reporting<30% pain reduction had their dose increased to 120 mg. The primary outcome measure was the Brief Pain Inventory (BPI) 24-hour average pain rating. Secondary measures included Roland-Morris Disability Questionnaire-24; Patient's Global Impressions of Improvement; Clinical Global Impressions-Severity (CGI-S); BPI-Severity and -Interference (BPI-I); and weekly means of the 24-hour average pain, night pain, and worst pain scores from patient diaries. Quality-of-life, safety, and tolerability outcomes were also assessed. RESULTS Compared with placebo-treated patients (least-squares mean change of -1.50), patients on Duloxetine (least-squares mean change of -2.32) had a significantly greater reduction in the BPI 24-hour average pain from baseline to endpoint (P=0.004 at week 13). Additionally, the Duloxetine group significantly improved on Patient's Global Impressions of Improvement; Roland-Morris Disability Questionnaire-24; BPI-Severity and average BPI-Interference; weekly mean of the 24-hour average pain, night pain, and worst pain. Significantly more patients in the Duloxetine group (13.9%) compared with placebo (5.8%) discontinued because of adverse events (P=0.047). The most common treatment-emergent adverse events in the Duloxetine group included nausea, dry mouth, fatigue, diarrhea, hyperhidrosis, dizziness, and constipation. CONCLUSION Duloxetine significantly reduced pain and improved functioning in patients with CLBP. The safety and tolerability were similar to those reported in earlier studies.
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Duloxetine a centrally acting analgesic in the treatment of patients with osteoarthritis knee pain a 13 week randomized placebo controlled trial
Pain, 2009Co-Authors: Amy S Chappell, Smriti Iyengar, H Liuseifert, Vladimir Skljarevski, Melissa J Ossanna, Robert M Bennett, Harry CollinsAbstract:Pain is a common cause of disability in osteoarthritis. Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), has demonstrated analgesic effects in diabetic peripheral neuropathy and fibromyalgia. Considering its central mechanism of action, Duloxetine may be effective in other pain states with evidence of central sensitization. Herein, we report the results of a 13-week, randomized, double-blind, placebo-controlled trial of Duloxetine (60-120 mg/day) versus placebo in the treatment of knee pain in 231 patients meeting clinical and radiographic criteria for osteoarthritis of the knee. Duloxetine was superior to placebo on the primary efficacy measure (weekly mean 24-h pain scores) beginning at Week 1 and continuing through the treatment period (P < or = .05). There was also a significant improvement in the WOMAC physical functioning subscale and several other secondary outcomes. Adverse-event rates did not differ significantly between treatment groups (49.5% for Duloxetine 60-120 mg/day, and 40.8% for placebo).
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Duloxetine for the management of diabetic peripheral neuropathic pain evidence based findings from post hoc analysis of three multicenter randomized double blind placebo controlled parallel group studies
Clinical Therapeutics, 2007Co-Authors: Daniel K Kajdasz, Smriti Iyengar, M Backonja, Durisala Desaiah, John T Farrar, David A Fishbain, Troels S Jensen, Michael C Rowbotham, Christine N Sang, Dan ZieglerAbstract:Abstract Objective: This post hoc analysis was aimed to summarize the efficacy and tolerability of Duloxetine as represented by number needed to treat (NNT) and number needed to harm (NNH) to provide a clinically useful assessment of the position of Duloxetine among current agents used to treat diabetic peripheral neuropathic pain (DPNP). Methods: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg Duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as ≥30% and ≥50% reductions from baseline in the weekly mean of the 24-hour average pain severity scores); NNH was calculated based on rates of discontinuation due to adverse events (AEs). Results: Patients receiving Duloxetine 60 mg QD and 60 mg BID had NNTs (95% CI) of 5.2 (3.8-8.3) and 4.9 (3.6-7.6), respectively, based on last observation carried forward; NNTs of 5.3 (3.8-8.3) for 60 mg QD and 5.7 (4.1-9.7) for 60 mg BID were obtained based on baseline observations carried forward. The NNHs (95% CI) based on discontinuation due to AEs were 17.5 (10.2-58.8) in the Duloxetine 60-mg QD group and 8.8 (6.3-14.7) in the 60-mg BID group. Conclusion: These post hoc results suggest that Duloxetine was effective and well tolerated for the management of DPNP and further support the importance of Duloxetine as a treatment option for clinicians and patients to assist with the management of DPNP.
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a randomized double blind placebo controlled trial of Duloxetine in the treatment of women with fibromyalgia with or without major depressive disorder
Pain, 2005Co-Authors: Lesley M Arnold, Smriti Iyengar, Amy K Rosen, Yili Lu Pritchett, Deborah N Dsouza, David J Goldstein, Joachim F WernickeAbstract:This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or without current major depressive disorder. Patients (90% Caucasian; mean age, 49.6 years; 26% with current major depressive disorder) received Duloxetine 60 mg once daily (QD) (N=118), Duloxetine 60 mg twice daily (BID) (N=116), or placebo (N=120). The primary outcome was the Brief Pain Inventory average pain severity score. Response to treatment was defined as >or=30% reduction in this score. Compared with placebo, both Duloxetine-treated groups improved significantly more (P or=30% in this score (Duloxetine 60 mg QD (55%; P<0.001); Duloxetine 60 mg BID (54%; P=0.002); placebo (33%)). The treatment effect of Duloxetine on pain reduction was independent of the effect on mood and the presence of major depressive disorder. Compared with patients on placebo, patients treated with Duloxetine 60 mg QD or Duloxetine 60 mg BID had significantly greater improvement in remaining Brief Pain Inventory pain severity and interference scores, Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and several quality-of-life measures. Both doses of Duloxetine were safely administered and well tolerated. In conclusion, both Duloxetine 60 mg QD and Duloxetine 60 mg BID were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder.
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a double blind randomized multicenter trial comparing Duloxetine with placebo in the management of diabetic peripheral neuropathic pain
Pain Medicine, 2005Co-Authors: Joel Raskin, Smriti Iyengar, Fujun Wang, Deborah N Dsouza, Y Pritchett, Amy L Waninger, Joachim F WernickeAbstract:Objective. Assess efficacy and safety of Duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, on the reduction of pain severity, in patients with diabetic peripheral neuropathic pain (DPNP). Methods. This was a multicenter, parallel, double-blind, randomized, placebo-controlled trial that enrolled 348 patients with pain due to peripheral neuropathy caused by type 1 or type 2 diabetes mellitus. Patients (N = 116 per group) were randomly assigned to receive Duloxetine 60 mg once daily (QD), Duloxetine 60 mg twice daily (BID), or placebo, for 12 weeks. The primary outcome measure was the weekly mean score of 24-hour average pain severity evaluated on an 11-point Likert scale. Secondary outcome measures and safety were evaluated. Results. Compared with placebo-treated patients, both Duloxetine-treated groups improved significantly more (P < 0.001) on the 24-hour average pain score. Duloxetine demonstrated superiority to placebo in all secondary analyses of the primary efficacy measure. A significant treatment effect for Duloxetine was observed in most secondary measures for pain. Discontinuations due to adverse events were more frequent in the Duloxetine 60 mg BID- (12.1%) versus the placebo- (2.6%) treated group. Duloxetine showed no adverse effects on diabetic control, and both doses were safely administered and well tolerated. Conclusions. In this clinical trial, Duloxetine 60 mg QD and Duloxetine 60 mg BID were effective and safe in the management of DPNP.
Vladimir Skljarevski - One of the best experts on this subject based on the ideXlab platform.
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Duloxetine pregabalin and Duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin an open label randomized noninferiority comparison
Mayo Clinic Proceedings, 2011Co-Authors: Robert J Tanenberg, Gordon Irving, R C Risser, Jonna Ahl, Michael J Robinson, Vladimir Skljarevski, Sandra K MalcolmAbstract:OBJECTIVE To determine whether Duloxetine is noninferior to (as good as) pregabalin in the treatment of pain associated with diabetic peripheral neuropathy. PATIENTS AND METHODS We performed a 12-week, open-label study of patients with diabetic peripheral neuropathic pain who had been treated with gabapentin (≥900 mg/d) and had an inadequate response (defined as a daily pain score of ≥4 on a numerical rating scale [0-10 points]). The first patient was enrolled on September 28, 2006, and the last patient visit occurred on August 26, 2009. Patients were randomized to Duloxetine monotherapy (n=138), pregabalin monotherapy (n=134), or a combination of Duloxetine and gabapentin (n=135). The primary objective was a noninferiority comparison between Duloxetine and pregabalin on improvement in the weekly mean of the diary-based daily pain score (0- to 10-point scale) at end point. Noninferiority would be declared if the mean improvement for Duloxetine was no worse than the mean improvement for pregabalin, within statistical variability, by a margin of –0.8 unit. RESULTS The mean change in the pain rating at end point was –2.6 for Duloxetine and –2.1 for pregabalin. The 97.5% lower confidence limit was a –0.05 difference in means, establishing noninferiority. As to adverse effects, nausea, insomnia, hyperhidrosis, and decreased appetite were more frequent with Duloxetine than pregabalin; insomnia, more frequent with Duloxetine than Duloxetine plus gabapentin; peripheral edema, more frequent with pregabalin than with Duloxetine; and nausea, hyperhidrosis, decreased appetite, and vomiting, more frequent with Duloxetine plus gabapentin than with pregabalin. CONCLUSION Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin. Trial Registration: clinicaltrials.gov Identifier: NCT00385671
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a double blind randomized placebo controlled study of the efficacy and safety of Duloxetine for the treatment of chronic pain due to osteoarthritis of the knee
Pain Practice, 2011Co-Authors: Amy S Chappell, H Liuseifert, Vladimir Skljarevski, Shuyu Zhang, Durisala Desaiah, Yuri Belenkov, Jacques P BrownAbstract:Objective: To evaluate the efficacy and safety of Duloxetine in the treatment of chronic pain due to osteoarthritis of the knee. Methods: This was a 13-week, randomized, double-blind, placebo-controlled trial in patients meeting American College of Rheumatology clinical and radiographic criteria for osteoarthritis of the knee. At baseline, patients were required to have a ≥ 4 weekly mean of the 24-hour average pain ratings. Patients were randomized to either Duloxetine 60 mg once daily (QD) or placebo. At week 7, the Duloxetine dosage was increased, in a blinded fashion, to 120-mg QD in patients reporting < 30% pain reduction. The primary efficacy measure was Brief Pain Inventory (BPI) 24-hour average pain. Secondary efficacy measures included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); Clinical Global Impressions of Severity (CGI-S). Safety and tolerability was also assessed. Results: Of the total (n = 256) patients, 111 (86.7%) in placebo group and 93 (72.7%) in Duloxetine group completed the study. Patients treated with Duloxetine had significantly (P ≤ 0.001) greater improvement at all time points on BPI average pain and had significantly greater improvement on BPI pain severity ratings (P ≤ 0.05), WOMAC total (P = 0.044) and physical functioning scores (P = 0.016), and CGI-S (P = 0.009) at the study endpoint. Frequency of treatment-emergent nausea, constipation, and hyperhidrosis were significantly higher in the Duloxetine group (P ≤ 0.05). Significantly more Duloxetine-treated patients discontinued the trial because of adverse events (P = 0.002). Conclusions: Treatment with Duloxetine 60 mg to 120 mg QD was associated with significant pain reduction and improved function in patients with pain due to osteoarthritis of the knee.
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Duloxetine versus placebo in patients with chronic low back pain a 12 week fixed dose randomized double blind trial
The Journal of Pain, 2010Co-Authors: Vladimir Skljarevski, Shuyu Zhang, Durisala Desaiah, Karla Alaka, Santiago Palacios, Tomasz Miazgowski, K PatrickAbstract:Abstract This randomized, double-blind, placebo-controlled study assessed efficacy and safety of Duloxetine in patients with chronic low back pain (CLBP). Adults (n = 401) with a nonneuropathic CLBP and average pain intensity of ≥4 on an 11-point numerical scale (Brief Pain Inventory [BPI]) were treated with either Duloxetine 60 mg once daily or placebo for 12 weeks. The primary measure was BPI average pain. Secondary endpoints included Patient's Global Impressions of Improvement (PGI-I), Roland Morris Disability Questionnaire (RMDQ-24), BPI-Severity (BPI-S), BPI-Interference (BPI-I), and response rates (either ≥30% or ≥50% BPI average pain reduction at endpoint). Health outcomes included Short Form-36, European Quality of Life–5 Dimensions, and the Work Productivity and Activity Impairment questionnaire. Safety and tolerability were assessed. Compared with placebo-treated patients, Duloxetine-treated patients reported a significantly greater reduction in BPI average pain ( P ≤ .001). Similarly, Duloxetine-treated patients reported significantly greater improvements in PGI-I, BPI-S, BPI-I, 50% response rates, and some health outcomes. The RMDQ and 30% response rate showed numerical improvements with Duloxetine treatment. Significantly more patients in the Duloxetine group (15.2%) than patients in the placebo group (5.4%) discontinued because of adverse events ( P = .002). Nausea and dry mouth were the most common treatment-emergent adverse events with rates significantly higher in Duloxetine-treated patients. Perspective This study provides clinical evidence of the efficacy and safety of Duloxetine at a fixed dose of 60 mg once daily in the treatment of chronic low back pain (CLBP). Duloxetine received approval for treatment of CLBP in November, 2010.
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efficacy and safety of Duloxetine in patients with chronic low back pain
Spine, 2010Co-Authors: Vladimir Skljarevski, Michael J Detke, Smriti Iyengar, H Liuseifert, Qi Zhang, Durisala Desaiah, Amy S Chappell, J H Atkinson, M BackonjaAbstract:STUDY DESIGN This was a randomized, double-blind, placebo-controlled clinical trial. OBJECTIVE To assess the efficacy and safety of Duloxetine in the treatment of chronic low back pain (CLBP). SUMMARY OF BACKGROUND DATA Imbalance of serotonin and norepinephrine within modulatory pain pathways has been implicated in the development and maintenance of chronic pain. Duloxetine, a selective reuptake inhibitor of serotonin and norepinephrine, has demonstrated clinical efficacy in 3 distinct chronic pain conditions: diabetic peripheral neuropathic pain, fibromyalgia, and chronic pain because of osteoarthritis. METHODS In this randomized double-blind trial, adult nondepressed patients with a non-neuropathic CLBP and a weekly mean of the 24-hour average pain score>or=4 at baseline (0-10 scale) were treated with either Duloxetine or placebo for 13 weeks. The dose of Duloxetine during first 7 weeks was 60 mg once daily. At week 7, patients reporting<30% pain reduction had their dose increased to 120 mg. The primary outcome measure was the Brief Pain Inventory (BPI) 24-hour average pain rating. Secondary measures included Roland-Morris Disability Questionnaire-24; Patient's Global Impressions of Improvement; Clinical Global Impressions-Severity (CGI-S); BPI-Severity and -Interference (BPI-I); and weekly means of the 24-hour average pain, night pain, and worst pain scores from patient diaries. Quality-of-life, safety, and tolerability outcomes were also assessed. RESULTS Compared with placebo-treated patients (least-squares mean change of -1.50), patients on Duloxetine (least-squares mean change of -2.32) had a significantly greater reduction in the BPI 24-hour average pain from baseline to endpoint (P=0.004 at week 13). Additionally, the Duloxetine group significantly improved on Patient's Global Impressions of Improvement; Roland-Morris Disability Questionnaire-24; BPI-Severity and average BPI-Interference; weekly mean of the 24-hour average pain, night pain, and worst pain. Significantly more patients in the Duloxetine group (13.9%) compared with placebo (5.8%) discontinued because of adverse events (P=0.047). The most common treatment-emergent adverse events in the Duloxetine group included nausea, dry mouth, fatigue, diarrhea, hyperhidrosis, dizziness, and constipation. CONCLUSION Duloxetine significantly reduced pain and improved functioning in patients with CLBP. The safety and tolerability were similar to those reported in earlier studies.
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Duloxetine a centrally acting analgesic in the treatment of patients with osteoarthritis knee pain a 13 week randomized placebo controlled trial
Pain, 2009Co-Authors: Amy S Chappell, Smriti Iyengar, H Liuseifert, Vladimir Skljarevski, Melissa J Ossanna, Robert M Bennett, Harry CollinsAbstract:Pain is a common cause of disability in osteoarthritis. Duloxetine, a serotonin and norepinephrine reuptake inhibitor (SNRI), has demonstrated analgesic effects in diabetic peripheral neuropathy and fibromyalgia. Considering its central mechanism of action, Duloxetine may be effective in other pain states with evidence of central sensitization. Herein, we report the results of a 13-week, randomized, double-blind, placebo-controlled trial of Duloxetine (60-120 mg/day) versus placebo in the treatment of knee pain in 231 patients meeting clinical and radiographic criteria for osteoarthritis of the knee. Duloxetine was superior to placebo on the primary efficacy measure (weekly mean 24-h pain scores) beginning at Week 1 and continuing through the treatment period (P < or = .05). There was also a significant improvement in the WOMAC physical functioning subscale and several other secondary outcomes. Adverse-event rates did not differ significantly between treatment groups (49.5% for Duloxetine 60-120 mg/day, and 40.8% for placebo).
M Backonja - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of Duloxetine in patients with chronic low back pain
Spine, 2010Co-Authors: Vladimir Skljarevski, Michael J Detke, Smriti Iyengar, H Liuseifert, Qi Zhang, Durisala Desaiah, Amy S Chappell, J H Atkinson, M BackonjaAbstract:STUDY DESIGN This was a randomized, double-blind, placebo-controlled clinical trial. OBJECTIVE To assess the efficacy and safety of Duloxetine in the treatment of chronic low back pain (CLBP). SUMMARY OF BACKGROUND DATA Imbalance of serotonin and norepinephrine within modulatory pain pathways has been implicated in the development and maintenance of chronic pain. Duloxetine, a selective reuptake inhibitor of serotonin and norepinephrine, has demonstrated clinical efficacy in 3 distinct chronic pain conditions: diabetic peripheral neuropathic pain, fibromyalgia, and chronic pain because of osteoarthritis. METHODS In this randomized double-blind trial, adult nondepressed patients with a non-neuropathic CLBP and a weekly mean of the 24-hour average pain score>or=4 at baseline (0-10 scale) were treated with either Duloxetine or placebo for 13 weeks. The dose of Duloxetine during first 7 weeks was 60 mg once daily. At week 7, patients reporting<30% pain reduction had their dose increased to 120 mg. The primary outcome measure was the Brief Pain Inventory (BPI) 24-hour average pain rating. Secondary measures included Roland-Morris Disability Questionnaire-24; Patient's Global Impressions of Improvement; Clinical Global Impressions-Severity (CGI-S); BPI-Severity and -Interference (BPI-I); and weekly means of the 24-hour average pain, night pain, and worst pain scores from patient diaries. Quality-of-life, safety, and tolerability outcomes were also assessed. RESULTS Compared with placebo-treated patients (least-squares mean change of -1.50), patients on Duloxetine (least-squares mean change of -2.32) had a significantly greater reduction in the BPI 24-hour average pain from baseline to endpoint (P=0.004 at week 13). Additionally, the Duloxetine group significantly improved on Patient's Global Impressions of Improvement; Roland-Morris Disability Questionnaire-24; BPI-Severity and average BPI-Interference; weekly mean of the 24-hour average pain, night pain, and worst pain. Significantly more patients in the Duloxetine group (13.9%) compared with placebo (5.8%) discontinued because of adverse events (P=0.047). The most common treatment-emergent adverse events in the Duloxetine group included nausea, dry mouth, fatigue, diarrhea, hyperhidrosis, dizziness, and constipation. CONCLUSION Duloxetine significantly reduced pain and improved functioning in patients with CLBP. The safety and tolerability were similar to those reported in earlier studies.
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a double blind randomized trial of Duloxetine versus placebo in the management of chronic low back pain
European Journal of Neurology, 2009Co-Authors: V Skljarevski, M Ossanna, H Liuseifert, Qi Zhang, A Chappell, S Iyengar, M Detke, M BackonjaAbstract:Background: Duloxetine has demonstrated analgesic effect in chronic pain states. This study assesses the efficacy of Duloxetine in chronic low back pain (CLBP). Methods: Adult patients with non-radicular CLBP entered this 13-week, double-blind, randomized study comparing Duloxetine 20, 60 or 120 mg once daily with placebo. The primary measure was comparison of Duloxetine 60 mg with placebo on weekly mean 24-h average pain. Secondary measures included Roland-Morris Disability Questionnaire (RMDQ-24), Patient’s Global Impressions of Improvement (PGI-I), Brief Pain Inventory (BPI), safety and tolerability. Results: Four hundred four patients were enrolled, 267 completed. No significant differences existed between any dose of Duloxetine and placebo on reduction in weekly mean 24-h average pain at end-point. Duloxetine 60 mg was superior to placebo from weeks 3–11 in relieving pain, but not at weeks 12–13. Duloxetine 60 mg demonstrated significant improvement on PGI-I, RMDQ-24, BPI-average pain and BPI-average interference. Significantly more patients taking Duloxetine 120 mg (24.1%) discontinued because of adverse events, versus placebo (8.5%). Conclusions: Duloxetine was superior to placebo on the primary objective from weeks 3–11, but superiority was not maintained at end-point. Duloxetine was superior to placebo on many secondary measures, and was well-tolerated.
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Duloxetine for the management of diabetic peripheral neuropathic pain evidence based findings from post hoc analysis of three multicenter randomized double blind placebo controlled parallel group studies
Clinical Therapeutics, 2007Co-Authors: Daniel K Kajdasz, Smriti Iyengar, M Backonja, Durisala Desaiah, John T Farrar, David A Fishbain, Troels S Jensen, Michael C Rowbotham, Christine N Sang, Dan ZieglerAbstract:Abstract Objective: This post hoc analysis was aimed to summarize the efficacy and tolerability of Duloxetine as represented by number needed to treat (NNT) and number needed to harm (NNH) to provide a clinically useful assessment of the position of Duloxetine among current agents used to treat diabetic peripheral neuropathic pain (DPNP). Methods: Data were pooled from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in which patients received 60 mg Duloxetine either QD or BID or placebo. NNT was calculated based on rates of response (defined as ≥30% and ≥50% reductions from baseline in the weekly mean of the 24-hour average pain severity scores); NNH was calculated based on rates of discontinuation due to adverse events (AEs). Results: Patients receiving Duloxetine 60 mg QD and 60 mg BID had NNTs (95% CI) of 5.2 (3.8-8.3) and 4.9 (3.6-7.6), respectively, based on last observation carried forward; NNTs of 5.3 (3.8-8.3) for 60 mg QD and 5.7 (4.1-9.7) for 60 mg BID were obtained based on baseline observations carried forward. The NNHs (95% CI) based on discontinuation due to AEs were 17.5 (10.2-58.8) in the Duloxetine 60-mg QD group and 8.8 (6.3-14.7) in the 60-mg BID group. Conclusion: These post hoc results suggest that Duloxetine was effective and well tolerated for the management of DPNP and further support the importance of Duloxetine as a treatment option for clinicians and patients to assist with the management of DPNP.
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Duloxetine in the acute and long term treatment of major depressive disorder a placebo and paroxetine controlled trial
European Neuropsychopharmacology, 2004Co-Authors: Michael J Detke, Curtis Wiltse, Craig H Mallinckrodt, Robert K Mcnamara, Mark A Demitrack, Istvan BitterAbstract:Background: Duloxetine is a balanced and potent dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE) that has previously been shown to be effective in the acute treatment of major depressive disorder (MDD). This placebo-controlled study assesses the safety and efficacy of Duloxetine (80 or 120 mg/day) and paroxetine (20 mg QD) during an initial 8-week acute phase and subsequent 6-month continuation phase treatment of MDD. Method: In this randomized, double-blind, placebo-controlled trial, adult outpatients (age ≥18 years) meeting DSM-IV criteria for MDD received placebo (n=93), Duloxetine 80 mg/day (40 mg BID; n=95), Duloxetine 120 mg/day (60 mg BID; n=93), or paroxetine (20 mg QD; n=86) for 8 weeks. Patients who had a ≥30% reduction from baseline in HAMD17 total score during the acute phase were allowed to continue on the same (blinded) treatment for a 6-month continuation phase. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 subscales, the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAMA), Visual Analog Scales (VAS) for pain, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, the 28-item Somatic Symptom Inventory (SSI), and the Sheehan Disability Scale (SDS). Safety and tolerability were assessed using treatment-emergent adverse events, discontinuations due to adverse events, vital signs, ECGs, laboratory tests, and the Arizona Sexual Experiences Scale (ASEX). Results: During the acute phase, patients receiving Duloxetine 80 mg/day, Duloxetine 120 mg/day, or paroxetine 20 mg QD had significantly greater reductions in HAMD17 total score compared with placebo. Both Duloxetine (80 and 120 mg/day) and paroxetine treatment groups had significantly greater improvement, compared with placebo, in MADRS, HAMA, CGI-S, and PGI-I scales. Estimated probabilities of remission at week 8 for patients receiving Duloxetine 80 mg/day (51%), Duloxetine 120 mg/day (58%), and paroxetine (47%) were significantly greater compared with those receiving placebo (30%). The rate of discontinuation due to adverse events among Duloxetine-treated patients (80 and 120 mg/day) did not differ significantly from the rate in the placebo group. Treatment-emergent adverse events reported significantly more frequently by Duloxetine-treated patients than by patients receiving placebo were constipation (80 and 120 mg/day), increased sweating (120 mg/day), and somnolence (120 mg/day). The incidence of acute treatment-emergent sexual dysfunction in Duloxetine- and paroxetine-treated patients was 46.5% and 62.8%, respectively. During the 6-month continuation phase, Duloxetine (80 and 120 mg/day) and paroxetine treatment groups demonstrated significant improvement in HAMD17 total score. Treatment-emergent adverse events occurring most frequently in each active treatment group during the continuation phase were viral infection (Duloxetine 80 mg/day), diarrhea (Duloxetine 120 mg/day), and headache (paroxetine 20 mg QD). Conclusion: These data support previous findings that Duloxetine is safe, efficacious, and well tolerated in the acute treatment of MDD. Furthermore, these data provide the first demonstration under double-blind, placebo-controlled conditions that the efficacy and tolerability of Duloxetine are maintained during chronic treatment.
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effects of Duloxetine on painful physical symptoms associated with depression
Psychosomatics, 2004Co-Authors: David J Goldstein, Michael J Detke, Smriti Iyengar, James I Hudson, Mark A DemitrackAbstract:Painful physical symptoms are common features of major depressive disorder and may be the presenting complaints in primary care settings. The effect of the dual serotonin (5-HT) and norepinephrine reuptake inhibitor Duloxetine on emotional and painful physical symptoms in outpatients with major depressive disorder was evaluated in three randomized, double-blind, placebo-controlled trials. The trials' primary objective was to evaluate the effect of Duloxetine on mood, and subjects were not enrolled on the basis of presence, type, or severity of pain. However, the pain-relieving effects of Duloxetine were evaluated by a priori defined analyses of results from a visual analogue scale and the Somatic Symptom Inventory. Compared with placebo, Duloxetine was associated with significant reduction in pain severity. The authors concluded that Duloxetine reduces the painful physical symptoms of depression.
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Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression
Journal of Psychiatric Research, 2002Co-Authors: Michael J Detke, Robert K Mcnamara, David J Goldstein, Mark A DemitrackAbstract:Existing therapies for major depressive disorder (MDD) have either limited efficacy and/or poor tolerability. The present study examined the effects of Duloxetine, a potent and balanced dual reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE), in patients with MDD. Adult patients (N = 267) with MDD were randomly assigned to receive Duloxetine (60 mg/day) or placebo in this 9-week, multi-center, double-blind, parallel-group clinical trial. Efficacy was evaluated using the 17-item Hamilton Depression Rating Scale (HAMD(17)), Visual Analog Scales (VAS) for pain, Clinical Global Impression of Severity (CGI-S), Patient's Global Impression of Improvement (PGI-I), and Quality of Life in Depression Scale (QLDS). Safety was evaluated by assessing discontinuation rates, adverse event rates, vital signs, and laboratory tests. Duloxetine (60 mg QD) significantly reduced the HAMD(17) total score compared with placebo at the end of 9-week therapy. Estimated probabilities of response and remission were 65 and 43%, respectively, for Duloxetine compared with 42 and 28% for placebo. Duloxetine also reduced overall pain, back pain, shoulder pain and time in pain while awake significantly more than placebo. Global measures of improvement, including PGI-I and QLDS, were significantly improved by Duloxetine compared with placebo. Discontinuations due to adverse events were more frequent for Duloxetine-treated patients (12.5%) than for placebo-treated patients (4.3%). Nausea, dry mouth, dizziness, and constipation were more frequent for Duloxetine than placebo. There was no significant incidence of hypertension, nor any other safety issues. Duloxetine 60 mg administered once daily appears to be a safe and effective treatment for MDD.
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Duloxetine 60 mg once daily for major depressive disorder a randomized double blind placebo controlled trial
The Journal of Clinical Psychiatry, 2002Co-Authors: Michael J Detke, David J Goldstein, John R Hayes, Mark A DemitrackAbstract:BACKGROUND: Despite treatment advances, major depressive disorder (MDD) is still a significant cause of morbidity and mortality. Current therapies frequently fall short of providing full remission. In addition, physical symptoms are commonly seen in MDD patients, increasing overall morbidity and health care utilization. Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for efficacy and tolerability/safety in the treatment of MDD and associated physical symptoms. METHOD: In this multicenter, double-blind, parallel-group study, adult patients with DSM-IV MDD were randomly assigned to receive placebo (N = 122) or Duloxetine (60 mg/day, N = 123) for 9 weeks. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score. Painful physical symptoms were assessed using visual analog scales, and global illness and quality of life were evaluated using the Clinical Global Impressions-Severity scale, the Patient Global Impressions-Improvement scale, and the Quality of Life in Depression Scale. Safety and tolerability were determined by monitoring discontinuation rates, adverse events, vital signs, and laboratory results. RESULTS: Duloxetine was significantly superior to placebo (p < .001) in reducing HAM-D-17 total scores, starting at week 2. The estimated probability of remission for Duloxetine-treated patients (44%) was almost 3 times that of placebo patients (16%). Duloxetine significantly reduced painful physical symptoms in comparison with placebo. Discontinuation due to adverse events for Duloxetine-treated patients (13.8%) compared favorably with the rates reported for SSRIs in other studies. Nausea, dry mouth, and somnolence were the most common adverse events; no significant incidence of hypertension was seen. CONCLUSION: Duloxetine, 60 mg/day, is a well-tolerated and effective treatment for MDD that reduces painful physical symptoms. These findings suggest that Duloxetine may be a first-line treatment for patients with MDD and associated painful physical symptoms.
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Duloxetine in the treatment of major depressive disorder a double blind clinical trial
The Journal of Clinical Psychiatry, 2002Co-Authors: David J Goldstein, Craig H Mallinckrodt, Mark A DemitrackAbstract:BACKGROUND: Duloxetine hydrochloride, a dual reuptake inhibitor of serotonin and norepinephrine, was evaluated for therapeutic efficacy and safety/tolerability in the treatment of major depression. METHOD: In an 8-week multicenter, double-blind, placebo-controlled study, 173 patients (aged 18-65 years) with DSM-IV major depressive disorder were randomly allocated to receive placebo (N = 70), Duloxetine (N = 70), or fluoxetine, 20 mg q.d. (N = 33). Duloxetine dose was titrated in the first 3 weeks in a forced-titration regimen from 40 mg (20 mg b.i.d.) to 120 mg/day (60 mg b.i.d.). Patients were required to have a Clinical Global Impressions (CGI)-Severity of Illness scale score of at least moderate severity (> or = 4) and a 17-item Hamilton Rating Scale for Depression (HAM-D-17) total score of at least 15. Patients could not have had any current primary DSM-IV Axis I diagnosis other than major depressive disorder, or any anxiety disorder as a primary diagnosis within the past year, excluding specific phobias. The primary efficacy measurement was the HAM-D-17 total score, and secondary measures included the Montgomery-Asberg Depression Rating Scale, CGI-Severity of Illness and CGI-Improvement, and Patient Global Impression of Improvement. Safety was evaluated by recording the occurrence of discontinuation rates and treatment-emergent adverse events and by measurement of vital signs and laboratory analytes. RESULTS: Duloxetine was superior to placebo in change on the HAM-D-17 (p = .009). Estimated probabilities of response and remission were 64% and 56%, respectively, for Duloxetine, compared with 52% and 30% for fluoxetine and 48% and 32% for placebo. Duloxetine was numerically superior to fluoxetine on the primary and most of the secondary outcome measures. In general, Duloxetine was well tolerated; 76% of patients achieved the maximum dose, and insomnia and asthenia were the only adverse events reported statistically significantly (p < .05) more frequently by Duloxetine-treated patients compared with placebo-treated patients. CONCLUSION: These data indicate that Duloxetine is efficacious for the treatment of major depressive disorder and is well tolerated and safe.
