Antidepressive Agents, Second-Generation

抗抑郁药,第二代
  • 文章类型: Journal Article
    重度抑郁症(MDD)是一种常见的以悲伤为特征的心理健康障碍,绝望,和快感缺乏症。存在各种疗法,但效果有限。氢溴酸右美沙芬与盐酸安非他酮(Auvelity®)联合使用是最近批准的治疗成人这种疾病的替代品。
    这篇综述总结了重度抑郁症的神经生物学,并深入研究了其药理学,功效,安全,右美沙芬加安非他酮对成年患者的耐受性。它是基于观察性研究,临床试验,以及其他通过系统文献检索获得的次要研究。
    安非他酮和右美沙芬的组合作为一种新的心理健康药物疗法是可用于MDD的治疗选择的有趣补充。该组合可以在一系列场景中使用,包括作为一线治疗,作为第二种选择,当患者使用5-羟色胺靶向剂未能达到缓解时,和治疗难治性抑郁症。其他适应症的进一步研究,包括成瘾症,可以提供令人兴奋的结果。虽然是一个新的组合,临床医生会非常熟悉这两种药物,提高他们的可接受性。这种药物疗法还可以为发现可能具有有益协同作用的其他组合带来增加的动力。
    UNASSIGNED: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults.
    UNASSIGNED: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches.
    UNASSIGNED: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.
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  • 文章类型: Journal Article
    背景:健康相关生活质量(HRQL)是重度抑郁症(MDD)患者的重要目标,但抗抑郁药是否能改善这些患者的HRQL尚不清楚.这里,我们描述了曲唑酮每日一次(TzOAD)和选择性5-羟色胺再摄取抑制剂(SSRI)治疗对MDD成人患者HRQL和功能的实际影响.
    方法:这个为期8周的前瞻性,观察,开放标签,多中心研究是在中度或重度MDD的成人中进行的,其中TzOAD或SSRI被规定为单药治疗.主要结果是从基线到第8周,通过患者报告的生活质量享受和满意度问卷简表(Q-LES-Q-SF)评估生活享受和满意度。次要结果包括Q-LES-Q-SF从基线到第1周和第2周的变化;使用蒙哥马利奥斯贝格抑郁量表(MADRS)的抑郁症状严重程度和通过PROMISSF-SD8b问卷在第1、2和8周的睡眠障碍;以及通过Sheehan残疾量表(SDS)的整体功能,使用Snaith-Hamilton快乐量表(SHAPS)的享乐能力,在基线和第8周使用感知缺陷问卷(PDQ-5)和认知功能障碍。
    结果:该研究包括208名患有MDD的成年人(平均[SD]年龄=50.2[14.3]岁;68.6%为女性;98.4%为白人)。从基线到第8周,两个治疗组的生活享受和满意度都得到了改善:SSRI组的Q-LES-Q-SF均值(SD)评分为27.5(20.4),TzOAD组为39.0(22.1)。抑郁症状和睡眠障碍也从基线降低到第8周:MADRS(SSRI,-15.7[8.3];TzOAD,-21.0[9.8]);PROMISSF-SD8b(SSRI,-9.9[12.6];TzOAD,-22.0[12.6])。Q-LES-Q-SF中的平均变化分数,MADRS,两组的PROMISSF-SD8b最早在第1周改善。在SDS上,从基线到第8周的平均得分也有所改善(SSRI,-9.2[7.4];TzOAD,-14.3[7.5]),SHAPS(SSRI,-6.6[4.3];TzOAD,-8.3[4.4]),和PDQ-5(SSRI,-5.8[4.5];TzOAD,-7.7[5.0])。
    结论:在接受TzOAD或SSRIs的患有MDD的成年人中,整体和个体HQRL域迅速改善,同时改善抑郁症状,在TzOAD组中观察到稍大的改善。
    BACKGROUND: Health-related quality of life (HRQL) is an important goal for patients with major depressive disorder (MDD), but whether antidepressants improve HRQL in these patients is unclear. Here, we describe the real-world effects of trazodone once-a-day (TzOAD) and selective serotonin reuptake inhibitor (SSRI) treatments on HRQL and functioning in adults with MDD.
    METHODS: This 8-week prospective, observational, open-label, multicenter study was conducted in adults with moderate or severe MDD for whom TzOAD or SSRI were prescribed as monotherapy. The primary outcome was life enjoyment and satisfaction assessed via the patient-reported Quality-of-Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) from baseline to week 8. Secondary outcomes included change in Q-LES-Q-SF from baseline to weeks 1 and 2; severity of depressive symptoms using the Montgomery Åsberg Depression Rating Scale (MADRS) and sleep disturbance via the PROMIS SF-SD 8b questionnaire at weeks 1, 2, and 8; and overall functioning via the Sheehan Disability Scale (SDS), hedonic capacity using the Snaith-Hamilton Pleasure Scale (SHAPS), and cognitive dysfunction using the Perceived Deficits Questionnaire (PDQ-5) at baseline and week 8.
    RESULTS: The study included 208 adults with MDD (mean [SD] age = 50.2 [14.3] years; 68.6% female; 98.4% White). Life enjoyment and satisfaction improved from baseline to week 8 for both treatment groups: Q-LES-Q-SF mean (SD) scores were 27.5 (20.4) for the SSRI group and 39.0 (22.1) for the TzOAD group. Depressive symptoms and sleep disturbances also reduced from baseline to week 8: MADRS (SSRI, -15.7 [8.3]; TzOAD, -21.0 [9.8]); PROMIS SF-SD 8b (SSRI, -9.9 [12.6]; TzOAD, -22.0 [12.6]). Mean change scores in Q-LES-Q-SF, MADRS, and PROMIS SF-SD 8b improved as early as week 1 in both groups. Mean scores also improved from baseline to week 8 on SDS (SSRI, -9.2 [7.4]; TzOAD, -14.3 [7.5]), SHAPS (SSRI, -6.6 [4.3]; TzOAD, -8.3 [4.4]), and PDQ-5 (SSRI, -5.8 [4.5]; TzOAD, -7.7 [5.0]).
    CONCLUSIONS: In adults with MDD who received TzOAD or SSRIs, overall and individual HQRL domains improved rapidly and in parallel with improvements in depressive symptoms, with a slightly greater improvement observed in the TzOAD group.
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    文章类型: Journal Article
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  • 文章类型: Case Reports
    曲唑酮是一种被批准用于治疗重度抑郁症的抗抑郁药,并且由于其镇静作用也被用于治疗失眠。在少数情况下,曲唑酮与帕金森病有关。在这里,我们描述了短暂暴露于中等剂量曲唑酮后的帕金森病病例。
    描述一例曲唑酮诱发的帕金森病患者,在排除其他常见和严重原因后怀疑诊断。
    曲唑酮致帕金森病1例报告.
    一名有睡眠问题的58岁男性在睡前每天服用50毫克曲唑酮。一周后,受试者在没有医疗建议的情况下将剂量加倍。曲唑酮治疗14天后,他开始感到上肢活动困难和反复跌倒。神经影像学,电诊断研究,实验室考试并不引人注目。曲唑酮停产了,病人完全康复了.值得注意的是,曲唑酮再激发后,患者出现运动症状复发.
    我们的病例显示,在短期摄入治疗失眠的中等剂量曲唑酮后,可逆转诱发帕金森病。曲唑酮停药后,患者完全康复。值得注意的是,再次使用曲唑酮后症状复发.
    UNASSIGNED: Trazodone is an antidepressant agent approved for treating major depressive disorders and is also prescribed for insomnia due to its sedative effect. In a few cases, trazodone was associated with parkinsonism. Herein, we describe a case of parkinsonism after a brief exposure to a moderate dose of trazodone.
    UNASSIGNED: To describe a case of a patient with trazodone-induced parkinsonism in which the diagnosis was suspected after the exclusion of other common and serious causes.
    UNASSIGNED: A case report of trazodone-induced parkinsonism.
    UNASSIGNED: A 58-year-old male with sleeping problems was prescribed trazodone 50 mg daily at bedtime. The subject doubled the dosage without medical advice a week later. After 14 days of trazodone treatment, he started to experience difficulty in moving his upper limbs and recurrent falling. Neuroimaging, electrodiagnostic studies, and laboratory exams were unremarkable. Trazodone was discontinued, and the patient fully recovered. Noteworthy, the patient developed a recurrence of the motor symptoms with trazodone-rechallenge.
    UNASSIGNED: Our case showed reversibly induced parkinsonism after a short intake of a moderate dose of trazodone which was prescribed for insomnia. The patient had a complete recovery after trazodone withdrawal. Noteworthy, the symptoms recurred upon trazodone-rechallenge.
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  • 文章类型: Journal Article
    曲唑酮对抑郁症的几种精神病理学方面的功效已在文献中显示。曲唑酮已广泛用于一些临床环境(例如用于老年人的失眠和抑郁症)。然而,曲唑酮在抑郁症几个方面的作用尚不清楚。
    来自意大利各地学术和医疗中心的八名专家开会,以确定在评估和管理重度抑郁症的日常临床实践中面临的困难和障碍,以及曲唑酮的使用如何解决一些未满足的需求。专家会议和本文件的目的是增加对曲唑酮治疗特定领域的了解。
    曲唑酮在伴有焦虑症状的重度抑郁症患者中作用的证据,失眠,激动,认知缺陷,酒精使用障碍,身体合并症,已经确定了自杀风险,显示曲唑酮在重度抑郁症的不同表现中的有效性。已经确定了曲唑酮似乎最有效的抑郁症患者的主要特征,为临床医生提供有关该药物在此类患者人群中可能使用的信息。
    UNASSIGNED: The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical contexts (e.g. for insomnia and depression in the elderly). However, the role of trazodone in several aspects of depression is not well known.
    UNASSIGNED: Eight experts from academic and medical centers across Italy met to identify the difficulties and barriers faced in daily clinical practice in the assessment and management of major depressive disorder and how the use of trazodone could address some unmet needs. The objective of the expert meetings and the present document was to increase knowledge of particular areas of treatment with trazodone.
    UNASSIGNED: Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder. The main characteristics of patients with depression for whom trazodone seems to be most effective have been identified, providing clinicians with information on possible uses of this drug in such population of patients.
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  • 文章类型: Journal Article
    背景:Habenula,控制单胺能脑中枢的中枢脑区域,已与重度抑郁症(MDD)有关,并可能作为抗抑郁反应的目标。然而,抗抑郁药物治疗对鞍状体积的影响尚不清楚.本研究的目的是研究MDD患者抗抑郁治疗后的a体体积变化,并评估其是否与临床改善相关。
    方法:在MDD的背景下,50名当前患有重度抑郁发作(MDE)的患者,至少1个月无抗抑郁药,在连续3个月的文拉法辛抗抑郁治疗之前和之后,评估了hu子体积(3TMRI与手动分割)。
    结果:观察到总hu体体积显着增加2.3%(绝对体积:P=0.0013;相对体积:P=0.0055)和左hu体体积显着增加3.3%(绝对体积:P=0.00080;相对体积:P=0.0028)。与女性患者相比,男性患者(4.8%)的变化明显更大。没有观察到hu体体积变化与反应和缓解之间的关联。一些hu子体积的变化与嗅觉愉悦的改善有关。
    结论:抑郁症患者接受文拉法辛治疗3个月后,Habenular体积增加。进一步的研究应评估这些体积变化中是否暗示了细胞增殖和密度或树突状结构的变化。
    BACKGROUND: Habenula, a hub brain region controlling monoaminergic brain center, has been implicated in major depressive disorder (MDD) and as a possible target of antidepressant response. Nevertheless, the effect of antidepressant drug treatment on habenular volumes remains unknown. The objective of the present research was to study habenular volume change after antidepressant treatment in patients with MDD, and assess whether it is associated with clinical improvement.
    METHODS: Fifty patients with a current major depressive episode (MDE) in the context of MDD, and antidepressant-free for at least 1 month, were assessed for habenula volume (3T MRI with manual segmentation) before and after a 3 months sequence of venlafaxine antidepressant treatment.
    RESULTS: A 2.3% significant increase in total habenular volume (absolute volume: P = 0.0013; relative volume: P = 0.0055) and a 3.3% significant increase in left habenular volume (absolute volume: P = 0.00080; relative volume: P = 0.0028) were observed. A significant greater variation was observed in male patients (4.8%) compared to female patients. No association was observed between habenular volume changes and response and remission. Some habenula volume changes were associated with improvement of olfactory pleasantness.
    CONCLUSIONS: Habenular volumes increased after 3 months of venlafaxine treatment in depressed patients. Further studies should assess whether cell proliferation and density or dendritic structure variations are implied in these volume changes.
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  • 文章类型: Journal Article
    抑郁症是最常见的精神疾病之一。纳米技术已经出现以优化药理学响应。因此,这项工作的目的是开发和表征含有盐酸帕罗西汀的脂质体和纳米胶囊,并使用小鼠的开放视野和尾部悬浮试验评估其抗抑郁样效果。使用反相蒸发和纳米沉淀方法制备脂质体和纳米胶囊,分别。制剂的粒径范围为121.81至310.73nm,多分散指数从0.096到0.303,ζ电位从-11.94到-34.50mV,pH从5.31到7.38,药物含量从80.82到94.36%,关联效率为98%。10小时后,与纳米胶囊(95.59%)相比,与脂质体(43.82%)缔合时,盐酸帕罗西汀显示出较慢的释放。在Vero细胞中,体外毒性对盐酸帕罗西汀纳米结构有浓度依赖性作用.两种纳米结构均在2.5mg/kg时降低了TST中的不动时间,而不影响开放场测试中的交叉次数,提示帕罗西汀的抗抑郁作用.此外,纳米胶囊减少了修饰的数量,加强这种药物的抗焦虑作用。这些结果表明,即使在低剂量下,纳米结构也能有效保持盐酸帕罗西汀的抗抑郁样作用。
    Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.
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  • 文章类型: Journal Article
    背景:糖尿病和抑郁症是全球十大健康负担之一。它们经常共存并表现出强烈的双向关系。抑郁症导致对自我护理活动的依从性下降。这会影响血糖控制并恶化2型糖尿病(T2D)。两种情况都有协同作用,并导致更大的并发症,住院治疗,医疗支出和更差的生活质量。在管理患有T2D和抑郁症的人方面没有共识。安非他酮是一种有效的抗抑郁药,具有许多适用于患有抑郁症的T2D的特性,包括良好的代谢特征,持续的体重减轻和性功能障碍的改善。我们将评估附加安非他酮的疗效和安全性与T2D和轻度抑郁症患者的标准治疗相比。这项研究可以为管理T2D和抑郁症的多发病率提供有价值的见解。这可以帮助减轻健康,这两种疾病的社会和经济负担。
    方法:这项交叉随机对照试验将招募患有T2D(5年或更长时间)的轻度抑郁症患者。他们将被随机分配给安非他酮和标准护理。治疗3个月后,将有1个月的冲洗期(不添加安非他酮,而标准治疗将继续)。在此之后,这两个手臂将被交换。参与者将被评估为糖化血红蛋白,坚持糖尿病自我护理活动,血脂谱,尿白蛋白与肌酐的比值,自主神经功能,性功能,生活质量和不良事件。
    背景:全印度医学科学研究所的机构伦理委员会,焦特布尔已批准本研究(AIIMS/IEC/2022/4172,2022年9月19日)。我们计划在研究现场通过封闭的小组讨论传播研究结果,科学会议,同行评审出版的手稿和社交媒体。
    背景:CTRI/2022/10/046411。
    BACKGROUND: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases.
    METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events.
    BACKGROUND: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media.
    BACKGROUND: CTRI/2022/10/046411.
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  • 文章类型: Journal Article
    安非他酮是一种流行的抗抑郁药,因为它具有良好的副作用和戒烟和减肥的适应症。由于安非他酮过量后延迟发作癫痫发作和其他不良后果的可能性,患者通常在怀疑摄入后12-24小时内观察.心动过速是一种临床预测因子,有望将癫痫发作风险病例与不需要长期观察的低风险病例区分开来。这项研究评估了在出现的前八小时内的心率是否可以识别不需要长期观察的病例。
    这是2010年至2022年间来自两个医院系统的所有超治疗安非他酮病例的回顾性队列研究。
    包含216张图表的数据。癫痫发作,低血压,心律失常发生在19%(n=41),1.4%(n=3),分别为0.9%(n=2)。一名患者死亡。延迟的不良反应很少见(n=4);它们发生在摄入后14小时至28小时。8小时内的最大心率与不良后果的风险相关。(赔率比,1.07;95%置信区间:1.05至1.09;P<0.001)。八小时最大心率阈值为104次/分钟,对于延迟不良反应的发生,其阴性预测值为100%(95%置信区间:96.7%至100%)。所有延迟作用的患者在急诊科到达后的五个小时内都有心动过速。
    癫痫发作的延迟不良结局,低血压,心律失常,死亡在这个队列中并不常见。在观察的前八小时内,心率作为筛查测试可靠地进行,以识别延迟不良结局的低风险患者。这项研究受到其回顾性性质的限制,无法确定大多数情况下的摄入时间和缺乏验证性实验室测试。
    本研究支持在没有其他临床毒性迹象需要入院时,如果没有共同摄入或给予掩盖心动过速的物质,则使用8小时观察期。
    UNASSIGNED: Bupropion is a popular antidepressant due to its favorable side effect profile and indications for smoking cessation and weight loss. Due to the possibility of delayed onset seizure and other adverse outcomes after bupropion overdose, patients are often observed for periods of 12-24 hours following suspected ingestion. Tachycardia is a clinical predictor that holds promise in differentiating cases at risk for seizures from low-risk cases that do not require prolonged observation. This study assessed whether heart rate within the first eight hours of presentation can identify cases that do not require extended observation.
    UNASSIGNED: This is a retrospective cohort study of all supra-therapeutic bupropion cases from two hospital systems between 2010 and 2022.
    UNASSIGNED: Data from 216 charts were included. Seizures, hypotension, and dysrhythmias occurred in 19 percent (n = 41), 1.4 percent (n = 3), 0.9 percent (n = 2) respectively. One patient died. Delayed adverse effects were rare (n = 4); they occurred from 14 hours to 28 hours post-ingestion. Maximum heart rate in eight hours was associated with a risk of adverse outcomes. (odds ratio, 1.07; 95 percent confidence interval: 1.05 to 1.09; P < 0.001). An eight hour maximum heart rate threshold of 104 beats/minute had a negative predictive value of 100 percent (95 percent confidence interval: 96.7 percent to 100 percent) for the occurrence of delayed adverse effects. All patients with delayed effects had tachycardia within five hours of emergency department arrival.
    UNASSIGNED: Delayed adverse outcomes of seizures, hypotension, dysrhythmia, and death were uncommon in this cohort. Heart rate during the first eight hours of observation performs reliably as a screening test to identify patients at low risk for delayed adverse outcomes. This study is limited by its retrospective nature, the inability to ascertain time of ingestion for most cases and the lack of confirmatory laboratory testing.
    UNASSIGNED: This study supports the use of an eight hour observation period when there are no other clinical signs of toxicity to warrant admission and if no co-ingestion or administration of substances that mask tachycardia are present.
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