Evaluation of efficacy of duloxetine in stress urinary incontinence in women

Objective:

The purpose of this study has been to assess the efficacy of duloxetine, a selective inhibitor of serotonin and norepinephrine reuptake, in the treatment of stress urinary incontinence (SUI) in women.

Materials and Methods:

The study included 50 women aged above 18 years with a predominant symptom of stress urinary incontinence (SUI). The case definition included a predominant symptom of SUI with a weekly incontinence episode frequency (IEF) of seven or greater and a positive cough stress test. All the patients received duloxetine 20 mg twice daily for 12 weeks. The primary outcome variables included the IEF and improvement in quality of life. Paired Student''s ‘t’ test was used to analyze changes in IEF.

Results:

The improvement with duloxetine treatment was found in 40 out of 50 patients. Remaining 10 patients did not show any improvement with duloxetine and discontinued the treatment. In 40 patients, the mean baseline IEF was 12.5/week. At the end of three months treatment, IEF was six/week. This shows a statistically significant reduction in the IEF. Also, there was a good improvement in quality of life with 65% of patients in the “very much better” and “much better” categories according to PGI-I scale. In the remaining 10 patients, there was no significant improvement after one month of treatment and patients underwent surgery.

Conclusions:

The findings support duloxetine as a potential treatment for women with stress urinary incontinence.     

度洛西汀对抑郁症患者认知损害的汉语句子N400的影响

目的 探讨度洛西汀对抑郁症患者汉语句子事件相关电位N400的影响.方法 随机将年龄在18～60岁符合CCMD-3抑郁症诊断标准的60例患者分为阿米替林治疗组(实验组1,n=30)及度洛西汀治疗组(实验组2,n=30),选择30例健康者作为对照组.实验组治疗8周前后予汉密尔顿抑郁量表(HAMD)评分,各组分别予N400检测,分别比较N400潜伏期及波幅的差异.结果 实验组1、实验组2 Pz点潜伏期均比对照组延长,波幅均比对照组降低(P＜0.05及0.01).治疗后,实验组1、实验组2 Fz点潜伏期均比治疗前缩短,波幅均比治疗前升高(P＜0.05及0.01).实验组2 Pz点潜伏期比实验组1缩短,波幅均比实验组1升高(P＜0.05及0.01).治疗后,实验组1HAMD评分高于实验组2 (P＜0.01),实验组2显效率及总有效率明显高于实验组1(P＜0.01).结论 抑郁症患者存在与语言加工有关的认知损害,度洛西汀具有改善抑郁症患者认知功能的作用.     

度洛西汀对多西他赛化疗所致大鼠神经病理性疼痛的影响

目的 研究度洛西汀对多西他赛化疗所致大鼠神经病理性疼痛的作用。方法 24只SD雄性大鼠随机分为4组（n=6）：正常对照组、度洛西汀组、多西他赛模型组及度洛西汀治疗组。在治疗后第8天,检测大鼠的机械性痛阈、热痛阈、冷痛阈,以及L4~6脊髓背根神经节（dorsal root ganglia, DRG）P物质（substance P, SP）的释放。结果 多西他赛能够产生机械性痛觉异常（P=0.009）、热痛觉过敏（P<0.001）、冷痛觉异常（P<0.001）,以及L4~6脊髓DRG的SP释放（P=0.018）。而连续8天口服度洛西汀能有效降低多西他赛导致的神经病理性疼痛,减轻机械性痛觉异常（P=0.037）,热痛觉过敏（P=0.001）和冷痛觉异常（P=0.002）,但并没有减少P物质的释放（P=0.653）。结论 度洛西汀可能是一种潜在的有效减轻化疗诱导神经病理性疼痛的药物。     

度洛西汀对大鼠心肌缺血再灌注心律失常的影响及机制

目的 探讨度洛西汀对大鼠心脏缺血再灌注心律失常的影响及机制。方法 30只Sprague Dawley（SD）大鼠随机分为假手术组（Sham组）、缺血再灌注组（IR组）和度洛西汀组（Dulo组）。IR组大鼠左前降支结扎30min后再灌注120min,Dulo组大鼠结扎左前降支30min前腹腔注射盐酸度洛西汀40mg/kg,之后处理同IR组,Sham组仅暴露左前降支,未行结扎。二导联心电监测并记录3组心律失常发生情况,应用LabChart8软件分析心电图参数。Triphenyltetrazolium chloride（TTC）染色对比IR组及Dulo组大鼠心肌梗死面积。蛋白免疫印迹试验检测各组心脏组织Akt、细胞外调节蛋白激酶（extracellular regulated protein kinases,Erk）、caspase-3、超氧化物歧化酶（superoxide dismutase,SOD）1、SOD2和连接蛋白43（connexin 43,Cx 43）蛋白改变。结果 与IR组比较,缺血期Dulo组大鼠室性期前收缩次数和室性心动过速次数减少（P<0.05）;再灌注期Dulo组的室性心动过速减少（P<0.05）,室性期前收缩次数差异无统计学意义（P>0.05）。度洛西汀抑制缺血和再灌注所致校正后Q-T间期（QTc）的延长（P<0.05）,并减小心肌梗死面积（P<0.05）。度洛西汀抑制Akt和Erk蛋白的磷酸化,减少cleaved caspase-3、cytochrome C蛋白表达并增加SOD1、SOD2和Cx43蛋白表达。结论 度洛西汀降低Akt和Erk蛋白磷酸化,抑制氧化应激及细胞凋亡,减低心脏缺血再灌注损伤过程中室性心律失常发生,减少梗死面积。     

The Effect of Initial Duloxetine Dosing Strategy on Nausea in Korean Patients with Major Depressive Disorder

Objective

To assess the relative severity of nausea in patients from Korea with major depressive disorder (MDD) who were treated with duloxetine at low (30 mg) or high (60 mg) doses, with or without food, for the first week of an 8 week treatment.

Methods

Adult patients (n=249), with MDD and a 17-item Hamilton Rating Scale for Depression (HAMD₁₇) score of ≥15, received open-label once daily duloxetine. At Week 0, patients were randomized to 4 groups: 30 mg with food (n=63), 60 mg with food (n=59), 30 mg without food (n=64), and 60 mg without food (n=63). At Week 1, all patients switched to duloxetine 60 mg for 7 weeks. The primary outcome measure was item 112 (nausea) of the Association for Methodology and Documentation in Psychiatry adverse event scale. Effectiveness was assessed by change in HAMD₁₇ total score.

Results

Overall, 94.4% (235/249) of patients completed Week 1 and 55.0% (137/249) of patients completed the study. For Week 1, nausea was significantly less severe for patients who received 30 mg compared with 60 mg duloxetine (p=0.003), regardless of food intake. In all groups, nausea severity was highest at Week 1 and declined throughout the study. HAMD₁₇ score was reduced in all groups and the most common adverse event reported was nausea (145/249; 58.2%).

Conclusion

To minimize nausea, Korean patients with MDD who require duloxetine treatment could be given 30 mg once daily, regardless of food, for the first week followed by 60 mg once daily for the course of therapy.     

Duloxetine,a centrally acting analgesic,in the treatment of patients with osteoarthritis knee pain: A 13-week,randomized, placebo-controlled trial

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 ? .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).     

度洛西汀临床不良反应分析

目的通过对文献报道度罗西汀引起的不良反应进行统计分析,了解度罗西汀的临床用药安全。方法通过对《中国知识资源总库》中文献报道度罗西汀引起的226例不良反应进行统计分析,以便帮助临床医生更好的把握患者的状况,调整治疗方案,以利于医生对药物应用的把握。结果分析表明度洛西汀不良反应偶有发生,大多数都比较轻微,患者都能够承受其副作用。结论临床应继续加强度洛西汀的不良反应检测与上报工作,以便确保患者用药安全。     

Topological network mechanisms of clinical response to antidepressant treatment in drug-naive major depressive disorder

AimThere is rapidly increasing evidence that remission of MDD is associated with substantial changes in functional brain connectivity. These New data have provided a holistic view on the mechanism of antidepressants on multiple levels that goes beyond their conventional effects on neurotransmitters.MethodThe study was approved by the Local Ethics Committee of Istanbul Medipol University (10840098-604.01.01-E.65129) and followed the Helsinki Declaration principles. In our study, we have evaluated the effect of six weeks of treatment with antidepressants (escitalopram and duloxetine), and tested the underlying brain functional connectivity through a Graph analysis approach in a well-defined first-episode, drug-naive, and non-comorbid population with MDD.ResultsBeyond indicating that there was a significant correlation between the antidepressant response and topological characteristics of the brain, our results suggested that global rather than regional network alterations may be implicated in the antidepressant effect.ConclusionDespite the small-sample size and non-controlled study design, our study provides important and relevant clinical data regarding the underlying mechanisms of the antidepressants on topological dynamics in the human brain.     

芬太尼透皮贴剂伍用度洛西汀治疗晚期重度癌痛的临床观察

目的探讨芬太尼透皮贴伍用度洛西汀治疗晚期重度癌痛患者的疼痛缓解程度、芬太尼透皮贴剂量、不良反应及患者生存质量变化。方法选择晚期重度癌痛患者100例,随机分为2组,每组50例,FD组给予芬太尼透皮贴伍用度洛西汀口服,F组仅给予芬太尼透皮贴剂镇痛治疗。分别记录治疗前及治疗后1、4、8周时患者的疼痛程度评分、芬太尼透皮贴剂量、镇静评分、不良反应、生活质量及满意度情况。结果用药1周后,两组患者疼痛控制均满意,NRS≤3;FD组患者芬太尼用量少于F组(P<0.05),治疗后8周,两组用量分别为(18.8±4.9)、(26.3±5.8)mg;FD组恶心呕吐、瘙痒等不良反应发生率低于F组(P<0.05);生活质量高于F组(P<0.05)。两组均无严重并发症发生。结论肿瘤晚期重度疼痛患者伍用度洛西汀治疗,可以减少芬太尼用量,减少恶心呕吐、瘙痒等不良反应,改善睡眠,增加患者满意度,推荐临床使用。     

度洛西汀和氟哌噻吨美利曲辛片治疗抑郁症伴躯体疼痛障碍的疗效比较

目的比较度洛西汀和氟哌噻吨美利曲辛片治疗抑郁症伴躯体疼痛障碍的临床疗效。方法选取2013年6月—2016年12月在北京市石景山区五里坨医院接受治疗的抑郁症伴躯体疼痛障碍患者128例,随机分为对照组和治疗组,每组各64例。脱落10例,实际完成118例,对照组58例,治疗组60例。对照组患者口服氟哌噻吨美利曲辛片,起始剂量为1片/d,2周内加至治疗剂量4片/d。治疗组在对照组的基础上口服度洛西汀肠溶片,起始剂量为10 mg/d,2周内加至治疗剂量60mg/d。两组患者均连续治疗8周。观察两组的临床疗效,比较两组的HAMD和HAMA评分、SF-MPQ评分和不良反应情况。结果治疗后,对照组和治疗组的显效率分别为17.24%、86.76%,有效率分别为87.93%、96.76%,两组显效率比较差异有统计学意义(P0.01),两组有效率比较差异无统计学意义。治疗8周后,对照组的HAMD和HAMA评分均显著降低,治疗4、8周后,治疗组HAMD和HAMA评分均显著降低,治疗前后比较差异具有统计学意义(P0.01);且治疗组的上述评分显著低于同期对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组的情感PRI评分和总PRI评分均显著降低,且治疗组的感觉PRI评分、VAS评分和PPI评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.01);且治疗后治疗组的SF-MPQ评分低于对照组,两组比较差异具有统计学意义(P0.05)。两组均未出现严重药物不良反应。结论与氟哌噻吨美利曲辛片相比,度洛西汀治疗抑郁症伴躯体疼痛起效快,药效更好,药物安全性高。