中国科技论文统计源期刊 中文核心期刊
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖
, 金卫东
该文从临床角度出发,提出在使用抗抑郁药物过程中,常常出现药品不良反应,包括自杀、5-羟色胺综合征、性功能障碍、代谢综合征、心血管副作用、消化道副作用、转躁等,发生率为31%~60%,这些不良反应不仅仅引起用药依从性的降低,甚至会导致严重的药物不良事件或药源性疾病,应该引起高度关注。
抗抑郁药是目前使用范围最广的精神药物之一,在欧洲国家和美国,服用抗抑郁药的患者占总人口的6%~10%。常用的抗抑郁药物有选择性5-羟色胺(5-HT)再摄取抑制药(selective serotonin reuptake inhibitor,SSRI)、选择性5-HT去甲肾上腺素再摄取抑制药(serotonin and noradrenaline reuptake inhibitor,SNRIs)、去甲肾上腺素能和特异性5-HT受体拮抗药(NASSA)及其他新型类型。然而,抗抑郁药也可导致一系列不良反应,进而影响治疗依从性,甚至会出现严重不良反应或药源性疾病(drug-induced diseases,DID)。DID又称药物诱发性疾病,是由某种药物或数种药物之间相互作用而引起的与治疗作用无关的药物不良反应(adverse drug reactions,ADR)。在美国,DID 已成为第5 位导致死亡的疾病,每年因DID 死亡的病例约为10万例。ADR是指因药品质量问题或用药不当所引起的有害反应,包括副作用、毒性反应、后遗反应、变态反应、特异质反应、抗感染药物引起的二重感染、依赖性以及致癌、致畸、致突变作用等。
抗抑郁药物在治疗过程中副作用的发生率高,为31%~60%,其受到病情等多因素影响。事实上,临床医生严重低估抗抑郁药的不良反应,>80%患者至少出现1种不良反应,平均每例患者出现4种不良反应,其中很多不良反应对患者造成显著的困扰,甚至影响到日常功能。约20%患者使用抗抑郁药弊大于利,因此必须引起高度重视。笔者针对抗抑郁药在临床使用中出现的较为严重的或常见不良反应,综述如下。
抗抑郁药物引起患者自杀倾向最早来自于一家制药公司对已上市抗抑郁药物安全性进行Meta分析。该研究纳入抗抑郁药物不良事件报告的RCT研究25项,结果发现,与安慰药比较,抗抑郁药物引起儿童青少年自杀或增加自杀风险的概率明显增加[
一项针对瑞典年轻(15~24岁)女性的研究显示,自杀事件的增加趋势与抗抑郁药使用有关,在2013年自杀的年轻女性中,约52%在自杀前12个月内接受抗抑郁药治疗[3]。目前,相关药物研究均无法解释该现象,而从临床诊断考虑,认为其与疾病性质可能相关。因为在多数情况下,青少年更可能是双相障碍,或为混合发作,容易被认为是抑郁症,从而使用抗抑郁药物。在这种情况下,青少年患者更容易冲动、激越、激惹,从而发生冲动性自杀。已经有很多研究发现这些现象,包括某些循证医学的结论已经证明,提示医生对青少年使用抗抑郁药物时,应该关注青少年自杀倾向。当然,也有相关专家认为美国FDA应该彻底删除该警告,认为这些建议无意中阻止抑郁症患者寻求治疗和减少医生开具抗抑郁药处方的可能性[4]。
SS是伴随患者大量使用5-HT能抗抑郁药物而逐渐出现的综合征。近年来已引起临床重视,SS发生率不高,但也时有发生[5,6]。有报道显示,SS也出现在其他可能影响血清5-HT水平的药物,如曲马多等 [7,8,9]。SS主要表现焦虑、激越,也可能有意识模糊,可以有植物神经症状,与血清素过度增加有关,严重情况可导致死亡。因此,对于SS的早期识别应该重视。5-HT 能抗抑郁药与某些心境稳定药联合使用或身体不适的情况下使用更容易出现SS。目前,国内外尚未对 SS 的流行病学进行充分的研究。2002 年 美国 毒 物 暴 露 监 测 系 统(toxic exposure surveillance system)从门诊、 住院及急诊科收到服用SSRI患者 26 733 例,其中7349 例有明显毒性反应,死亡93 例[10]。根据一项药品上市后监督调查估计,在治疗剂量下,患者服用萘法唑酮(nefazodone),SS发生率为 0.4‰。 而在超量使用SSRI 患者中,14%~16%患者发生SS。SS的诊断主要根据以下标准,(1)在使用5-HT 能药物后或在增加药物剂量过程中发生,至少具备下列 3 项症状:①精神状态改变(意识错乱,轻躁狂);②激越;③肌阵挛;④腱反射亢进;⑤出汗;⑥寒战;⑦震颤;⑧腹泻;⑨共济失调;⑩发热。(2)排除其他原因。(3)上述症状出现前没有使用或没有加量使用 5-HT 能药物(即症状出现在使用或加量使用 5-HT 能药物之后)[11]。
在早期诊断SS后应作对症处理。停止使用抗抑郁药物是早期最主要的处理原则。另外,需要注意SS与抗精神病药物恶性综合征(neuroleptic malignant syndrome,NMS)相区别。SS表现与NMS有所不同,包括以下内容:①神经肌肉症状,如震颤和僵硬也出现在NMS中,但寒战、共济失调、肌阵挛、反射亢进和髌骨阵挛等特征有助于诊断SS; ②胃肠功能障碍,包括恶心、呕吐和腹泻,这是NMS不典型的独特特征。③精神状态和植物神经功能紊乱的变化相似,但体温升高幅度比NMS小; ④NMS中白细胞增多与血清肌酸磷酸激酶(creatine phosphokinase,CPK)和肝酶升高不一致,而SS最低; ⑤SS病程通常是良性的,多数患者在致病因素解除后1~7 d恢复,而NMS恢复可能需要2周以上时间[12]。
抗抑郁药物致性功能障碍是比较常见的副作用,也是患者相对关注度更高的副作用。抗抑郁药可导致性欲下降、性唤起困难、射精延迟、性感缺失及勃起功能障碍,不良反应发生率可高达80%。相比于去甲肾上腺素能药物,服用SSRIs患者出现性功能障碍可能性更大。一般而言,米氮平引起性功能障碍概率低,艾司西酞普兰和帕罗西汀引起性功能障碍概率最高。对于某些患者,上述不良反应可随药物减量而消失或减轻。若服用半衰期短的抗抑郁药,如舍曲林或帕罗西汀,可停药几天,这一方式可改善半数患者性功能及提高对性生活的满意度[13,14,15]。有研究提示,关注性功能时,建议首先考虑阿戈美拉汀、安非他酮、去甲文拉法辛、吗氯贝胺、曲唑酮、维拉佐酮和沃替西汀等[16]。
笔者做过类似的循证医学研究。采用固定效应模型法对符合纳入标准的米氮平与SSRIs治疗抑郁症的随机对照研究中药物致性功能障碍的差异进行Meta分析。结果显示,14项研究纳入患者1108例,米氮平组发生性功能障碍5例,SSRIs组106例,两组性功能障碍发生率分别是0.90%和19.2%,综合检验两组差异有统计学意义,
抗抑郁药引起代谢综合征发生率小于非典型抗精神病药物 [18]。但米氮平及有镇静作用的抗抑郁药可引起体质量增加,血糖、血脂升高。这些代谢综合征发生率不定,但某一二个指标异常很常见。抗抑郁药有增加代谢综合征的风险,其机制主要包括食欲改变/体质量的影响、镇静/嗜睡、饮食结构变化、胰岛素受体敏感性改变、葡萄糖转运蛋白改变效应、抗胆碱能活性、神经肽/脂肪因子(如瘦素和胰岛素抵抗)、皮质醇调节障碍(和其他反调节激素)、肝脂质生物合成增加/外周脂质减少利用、中枢/外周单胺受体调节的变化、促炎性网络的激活(例如细胞因子)等。其中帕罗西汀和米氮平对血糖、体质量、脂质代谢有一定影响,与代谢综合征关系更为密切[19]。但一般情况下,用药2~4年后有代谢综合征发生率增加[20]
通常情况下,SSRIs对心血管副作用轻微,与三环类抗抑郁药物(tricydic antidepressive agents,TCA)比较,引起各种心血管副作用可忽略不计,很少有引起心电图异常的报道。因此,对于冠心病伴发焦虑抑郁障碍,建议使用SSRI,尤其推荐舍曲林。对伴有心血管疾病的老年患者,坚持服用抗抑郁药物被证实能够降低病死率[21]。
一项针对德语系国家的大样本研究(1993—2010年使用抗抑郁药患者169 278 例,其中发生心血管不良反应198例)结果显示,治疗期间心血管不良反应的发生率,单胺氧化酶抑制剂为0.27%,TCAs为0.15%,SNRIs为0.14%,SSRIs为 0.08%明显较低。NASSA抗抑郁药米氮平(0.07%)心血管不良反应风险显著低于其他抗抑郁药。最常见的ADR是严重低血压,其次是高血压、心律失常,还有一些罕见的心力衰竭[22]。其结果与同类研究基本相似,并未提示存在人种差异。
抗抑郁药致消化道副作用发生率>10%,属于常见的不良反应。患者在服用新型抗抑郁药不久出现恶心发生率为25%。恶心更常见于服用文拉法辛及SSRIs患者,而安非他酮、米氮平及瑞波西汀则相对少见。大部分患者服药2~3周后症状即逐渐消失,但1/3患者这一症状可持续存在[27,28]。分次服药、与食物同服或将大部分剂量安排在临睡前服用有助于减轻这一症状,进食含姜的食物、服用雷尼替丁及奥美拉唑也有好处。另外,在治疗方案中加入小剂量米氮平,可能同样有效。
约15%患者在服药过程中可能出现腹泻。止泻药或许有用,但对于症状持续存在患者,需要考虑换药。5%患者存在便秘,这些患者可加强身体锻炼,多饮水及进食纤维素,必要时可使用泻药。
抗抑郁药物引起转躁,这一点有不少争议。认为这不是抗抑郁药物的副作用,而是由疾病或患者自身的特点决定。但无论如何,这与抑郁药物有关,无论是引起或相关,在抗抑郁药物治疗过程都需要注意[29]。因此,目前在抗抑郁药物治疗过程中,都需要评价和关注躁狂症状。
抗抑郁药物引起转躁主要表现为:轻躁狂、躁狂或混合发作状态及慢性激惹状态。为了明确“抗抑郁药物相关的心境障碍”的术语,国际双相障碍协会(ISBD)一直推荐使用“治疗性急性心境转换”来取代“抗抑郁药物导致的转相”。ISBD关于“治疗性急性心境转换”的定义提供操作性诊断标准,在将转相抗抑郁药物的使用之前,需要充分考虑到时间、病程、严重性等因素[30],但无论如何,这种病理现象的存在与抗抑郁药物有一定关系。
抗抑郁药会因治疗对象的不同呈现各种各样的副作用,因此,针对不同患者宜制定个性化的治疗方案,在遵循指南和专家共识的基础上进行调整。部分药物副作用是由于药物剂量过大和联合用药引起,尤其需要临床医生关注。此外,仍有可能还存有一些罕见或严重不良反应,需在临床治疗过程中加强关注。
The authors have declared that no competing interests exist.
| [1] |
|
| [2] |
|
| [3] |
OBJECTIVE: To establish whether the young women (15-24 year old) who committed suicide in Sweden (1999-2013) received antidepressant treatment or not, and to what extent, prior to and/or at the time of suicide. To investigate the belief that increased prescription of antidepressants would drastically reduce the number of suicides. METHODS: An analysis of data from the Swedish Prescribed Drug Register, the Causes of Death Register, with registers cross checked, and from the National Board of Forensic Medicine. RESULTS: This analysis shows a covariance between increased prescription of antidepressants and an increasing trend in the number of suicides among young women. In the period 1999-2003 antidepressants were found in toxicological analyses done in 23% of the young women who committed suicide, and in 39% of cases for 2009-2013. CONCLUSION: An increasingly larger proportion of young women who later committed suicide, had in the last few years been treated with antidepressants, prior to and at the time of the suicide. The previous assumptions that treatment with antidepressants would lead to a drastic reduction in suicide rates, are incorrect for the population of young women. On the contrary, it was found that an increasing tendency of completed suicides follow the increased prescription of antidepressants.
[本文引用:1]
|
| [4] |
Perspective from The New England Journal of Medicine — Antidepressants' Black-Box Warning — 10 Years Later
[本文引用:1]
|
| [5] |
|
| [6] |
|
| [7] |
|
| [8] |
Tramadol is commonly prescribed for pain control because it presents a lower risk for addiction and respiratory depression compared to other opioids. However, tramadol's serotonin and norepinephrine reuptake inhibitory effects result in a unique adverse effect profile. Two such adverse events are serotonin syndrome and seizures. The prevalence of tramadol-induced serotonin syndrome and seizures is modest in the general population but if left untreated, the morbidity and mortality can be high, and therefore prompt recognition and management is essential. Various risk factors such as medical comorbidities, use and/or abuse of supratherapeutic doses of tramadol, and concomitant administration of proconvulsant serotonergic cytochrome P-450 inhibitors will help clinicians identify individuals at an elevated risk for serotonin toxicity and seizures. Serotonin syndrome and seizures can be effectively treated by and administering benzodiazepines, providing supportive care, and discontinuing tramadol and other contributing agents. Cyproheptadine should be administered in moderate to severe cases of serotonin syndrome. Our objective is to summarize the literature on the pharmacology, epidemiology, risk factors, clinical presentations, and evidence-based management of tramadol-related seizures and serotonin syndrome.
[本文引用:1]
|
| [9] |
|
| [10] |
|
| [11] |
react-text: 170 This is an illustrative case of a patient with neuroleptic malignant syndrome whom we believe is the first described in the world's literature to have this syndrome on three occasions, each time after having received a different neuroleptic agent. /react-text react-text: 171 /react-text
[本文引用:1]
|
| [12] |
|
| [13] |
|
| [14] |
Introduction: Depression is one of the more prevalent mental disorders in the United States, with estimates as high as 6.7% of Americans affected annually. Consequently, antidepressant use in the United States is also widespread. Both depression and its treatments are associated with sexual dysfunction (SD) in men and women, including orgasm and arousal problems, hypoactive sexual desire, premature ejaculation, erectile difficulties, and dyspareunia. Sexual dysfunction is frequently cited as a reason for nonadherence or discontinuation of treatment for depression. Aim: The objective of our review is to aid physicians, including primary care physicians, psychiatrists, and urologists/gynecologists, in the multidisciplinary approach to treating patients with SD and depression. Methods: Our review focuses on articles published within the last 10 years on SD and depression in adults, with an emphasis on the relationship of treatments for depression on SD. Summary: Different classes of antidepressants vary in their ability to cause sexual side effects. Results: Treatment with selective serotonin reuptake inhibitors (SSRIs) and serotonin/norepinephrine reuptake inhibitors (SNRIs) is associated with SD. Use of other antidepressants, such as bupropion, mirtazapine, nefazodone, and vilazodone, have been associated with less SD compared with SSRIs; furthermore, some of the mentioned antidepressants have been used in the treatment of SD induced by SSRIs and SNRIs.
[本文引用:1]
|
| [15] |
Abstract Because 1 in 6 women in the United States takes antidepressants and a substantial proportion of patients report some disturbance of sexual function while taking these medications, it is a near certainty that the practicing clinician will need to know how to assess and manage antidepressant-related female sexual dysfunction. Adverse sexual effects can be complex because there are several potentially overlapping etiologies, including sexual dysfunction associated with the underlying mood disorder. As such, careful assessment of sexual function at the premedication visit followed by monitoring at subsequent visits is critical. Treatment of adverse sexual effects can be pharmacological (dose reduction, drug discontinuation or switching, augmentation, or using medications with lower adverse effect profiles), behavioral (exercising before sexual activity, scheduling sexual activity, vibratory stimulation, psychotherapy), complementary and integrative (acupuncture, nutraceuticals), or some combination of these modalities. Copyright 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
[本文引用:1]
|
| [16] |
Sexual dysfunction (SD) is pervasive and underreported, and its effects on quality of life are underestimated. Due in part to its bidirectional relationship with depression, SD can be difficult to diagnose; it is also a common side effect of many antidepressants, leading to treatment noncompliance. While physicians often count on patients to spontaneously report SD, treatment is optimized when the clinician instead performs a thorough assessment of sexual functioning before and during drug therapy using a standardized questionnaire such as the Arizona Sexual Experiences Scale (ASEX). Separating the effects of the disorder from those of medications is challenging; we present a concise, evidence-based schematic to assist physicians in minimizing treatment-emergent sexual dysfunction (TESD) while treating depression. Vascular, hormonal, neurogenic, and pharmacological factors should be considered when a patient presents with SD. We also recommend that physicians obtain patient information about baseline and historical sexual functioning before prescribing a drug that may lead to SD and follow up accordingly. When the goal is to treat depression while attenuating the risk of sexual symptoms, physicians may wish to consider agomelatine, bupropion, desvenlafaxine, moclobemide, trazodone, vilazodone, and vortioxetine.
[本文引用:1]
|
| [17] |
目的:分析国内文献米氮平与选择性5-羟色胺再摄取抑制剂(SSRI)治疗抑郁症引发性功能障碍的差异。方法:用关键词从中国生物医学数据库光盘检索,采用固定效应模型(FEM)法对符合纳入标准的米氮平与SSRI治疗抑郁症的随机对照研究文献中药物引发性功能障碍的差异进行Meta分析。结果:14项研究例数1108例,其中研究组556例,对照组552例,米氮平治疗组发生性功能障碍5例,SSRI治疗组发生性功能障碍106例,两组性功能障碍的发生率分别是0.90%和19.2%,综合检验两组差异有统计学意义,Z=8.03,P0.01;OR=0.07,95%CI:0.04～0.14。结论:在治疗抑郁症中,SSRI比米氮平更容易引发性功能障碍,应特别加以关注。
[本文引用:1]
|
| [18] |
|
| [19] |
DOI:10.1002/da.22512
URL
[本文引用:1]
|
| [20] |
Major depressive disorder is a prevalent recurrent medical syndrome associated with inter-episodic dysfunction. The metabolic syndrome is comprised of several established risk factors for cardiovascular disease (i.e. abdominal obesity, dyslipidaemia, dysglycaemia and hypertension). The criterion items of the metabolic syndrome collectively represent a multi-dimensional risk factor for cardiovascular disease and type 2 diabetes mellitus. Extant evidence indicates that both major depressive disorder and the metabolic syndrome, albeit distinct, often co-occur and are possibly subserved by overlapping pathophysiology and causative mechanisms. Conventional antidepressants exert variable effects on constituent elements of the metabolic syndrome, inviting the need for careful consideration prior to treatment selection and sequencing. Initiating and maintaining antidepressant therapy should include routine surveillance for clinical and/or biochemical evidence suggestive of the metabolic syndrome.
[本文引用:1]
|
| [21] |
Abstract BACKGROUND0002AND OBJECTIVE: Conflicting findings from studies evaluating the association between use of antidepressant drugs and mortality have been reported. We tested the hypothesis that better adherence to antidepressant therapy may reduce mortality. METHODS: The cohort included 29,845 individuals aged090009090906090009650002years from several Italian health units who were newly treated with antidepressant drugs after hospital discharge with a diagnosis for cardiovascular disease during 2008-2010. These individuals were observed from the first prescription until the end of data availability (i.e. 2012-2014, depending on the local database). During this period, information on (1) prescription of antidepressants and other medications and (2) death from any cause (outcome) was recorded. Proportional hazards models were fitted to estimate the association between better adherence to antidepressants (defined as proportion of days covered09000909090609000975%) and outcome, by adjusting and stratifying for several covariates. RESULTS: Patients with better adherence to antidepressants had a reduced mortality of 9% (95% CI 3-14). Patients who did not use other medicaments during follow-up had reduced mortality associated with better adherence to antidepressants of 21% (-00021-38), 14% (7-20), 20% (13-26) and 13% (7-19) for no users of antihypertensive agents, lipid-lowering agents, other cardiovascular drugs and antidiabetics, respectively. CONCLUSIONS: Better adherence to antidepressants is associated with reduced all-cause mortality, mainly in patients who did not use other pharmacological treatments. Behavioural changes to enhance adherence among the elderly with cardiovascular disease might offer important benefits in reducing their mortality.
[本文引用:1]
|
| [22] |
|
| [23] |
|
| [24] |
|
| [25] |
|
| [26] |
Abstract Patients with long QT syndrome (LQTS) are at a high risk of cardiac events. Many patients with LQTS are treated with antidepressant drugs (ADs). We investigated the LQTS genotype-specific risk of recurrent cardiac arrhythmic events (CAEs) associated with AD therapy. The study included 59 LQT1 and 72 LQT2 patients from the Rochester-based LQTS Registry with corrected QT (QT c ) prolongation and a history of AD therapy. Using multivariate Anderson-Gill models, we estimated the LQTS genotype-specific risk of recurrent CAEs (ventricular tachyarrhythmias, aborted cardiac arrest, or sudden cardiac death) associated with time-dependent ADs. Specifically, we examined the risk associated with all ADs, selective serotonin reuptake inhibitor (SSRI), and ADs classified on the CredibleMeds list (www.CredibleMeds.org) as "Conditional" or "Known risk of Torsades de pointes (TdP)." After adjusting for baseline QT c duration, sex, and time-dependent beta-blocker usage, there was an increased risk of recurrent CAEs associated with ADs in LQT1 patients (hazard ratio090009=0900093.67, 95% confidence interval 1.98-6.82, p090009<0900090.001) but not in LQT2 patients (hazard ratio090009=0900090.89, 95% confidence interval 0.49-1.64, p090009=0900090.716; LQT1 vs LQT2 interaction, p090009<0900090.001). Similarly, LQT1 patients who were on SSRIs or ADs with "Known risk of TdP" had a higher risk of recurrent CAEs than those patients off all ADs, whereas there was no association in LQT2 patients. ADs with "Conditional risk of TdP" were not associated with the risk of recurrent CAEs in any of the groups. In conclusion, the risk of recurrent CAEs associated with time-dependent ADs is higher in LQT1 patients but not in LQT2 patients. Results suggest a LQTS genotype-specific effect of ADs on the risk of arrhythmic events.
[本文引用:1]
|
| [27] |
|
| [28] |
|
| [29] |
The singular phenomenon of switching from depression to its opposite state of mania or hypomania, and vice versa, distinguishes bipolar disorder from all other psychiatric disorders. Despite the fact that it is a core aspect of the clinical presentation of bipolar disorder, the neurobiology of the switch process is still poorly understood. In this review, we summarize the clinical evidence regarding somatic interventions associated with switching, with a particular focus on the biologic underpinnings presumably involved in the switch process. Literature for this review was obtained through a search of the MEDLINE database (1966-2008) using the following keywords and phrases: switch, bipolar disorder, bipolar depression, antidepressant, SSRIs, tricyclic antidepressants, norepinephrine, serotonin, treatment emergent affective switch, mania, hypomania, HPA-axis, glucocorticoids, amphetamine, dopamine, and sleep deprivation. All English-language, peer-reviewed, published literature, including randomized controlled studies, naturalistic and open-label studies, and case reports, were eligible for inclusion. Converging evidence suggests that certain pharmacologic and nonpharmacologic interventions with very different mechanisms of action, such as sleep deprivation, exogenous corticosteroids, and dopaminergic agonists, can trigger mood episode switches in patients with bipolar disorder. The switch-inducing potential of antidepressants is unclear, although tricyclic antidepressants, which confer higher risk of switching than other classes of antidepressants, are a possible exception. Several neurobiological factors appear to be associated with both spontaneous and treatment-emergent mood episode switches; these include abnormalities in catecholamine levels, up-regulation of neurotrophic and neuroplastic factors, hypothalamic-pituitary-adrenal axis hyperactivity, and circadian rhythms. There is a clear need to improve our understanding of the neurobiology of the switch process; research in this field would benefit from the systematic and integrated assessment of variables associated with switching.
[本文引用:1]
|
| [30] |
|
| [31] |
|
| [32] |
|
| [33] |
|
| [34] |
Major depressive disorder (MDD) impacts health, quality of life and workplace productivity. Antidepressant treatment is the primary therapeutic intervention. This study assessed the efficacy and tolerability of new generation antidepressants and their cost-effectiveness in the Singapore healthcare system. We conducted a systematic search for head-to-head randomised controlled trials on ten antidepressants (agomelatine, duloxetine, escitalopram, fluvoxamine, fluoxetine, mirtazapine, paroxetine, sertraline, trazodone and venlafaxine) employed as monotherapy in acute MDD management. We performed a network meta-analysis to compare their relative efficacy. The outcome measures for efficacy were response and remission rate, and mean change in Hamilton Depression Rating Scale (HDRS) score; and for tolerability, study withdrawal rates due to adverse events. To evaluate their relative cost effectiveness, a decision tree simulating a cohort of MDD patients using antidepressant as monotherapy was constructed from a societal perspective over 6 months. We used effectiveness data from our network meta-analysis and local data on resource use for depression in Singapore. The incremental cost expected for each additional quality-adjusted life-year (QALY) gained was calculated and presented as the incremental cost-effectiveness ratio (ICER). We identified 76 relevant articles for the network meta-analysis. Of the ten agents included in the analysis, mirtazapine and agomelatine were most efficacious in achieving response and remission, respectively. Mirtazapine and duloxetine resulted in the greatest magnitude of change in the HDRS score. Agomelatine, escitalopram and sertraline were the best tolerated of the drugs analysed, while duloxetine was the least well tolerated drug. Using a composite outcome of efficacy (response and remission rates) and tolerability, agomelatine, escitalopram and mirtazapine were the favoured treatments. In the cost-effectiveness analysis, apart from agomelatine, all the treatments were dominated by mirtazapine. Against mirtazapine, agomelatine was not cost effective given that its ICER exceeded the threshold value. Agomelatine, escitalopram and mirtazapine had favourable balance between efficacy and tolerability. In addition, mirtazapine was a cost-effective option in the Singapore healthcare system.
[本文引用:1]
|
| [35] |
帕 罗西汀、氟西汀等选择性 5 羟色胺再摄取抑制剂 (ＳＳＲＩｓ)是近年来涌现出来的新型抗抑郁药物 ,具有作用快 ,抗胆碱能副作用轻 ,无镇静作用等优点 ,除对中枢 5 羟色胺 ( 5 ＨＴ)递质具有再摄取抑制作用外 ,对多巴胺 (ＤＡ)、组胺Ｈ1、乙酰胆碱(Ａｃｈ)等递质及受体无
[本文引用:2]
|
| [36] |
目的分析三环类抗抑郁药物(TCA)与选择性5-羟色胺再摄取抑制药(SSRI)治疗抑郁症引发失眠、焦虑、激越与躁狂的差异。方法应用循证医学的Meta分析,采用固定效应模型(fixed effects model,FEM)法对符合标准的63项对照研究文献进行评价。结果SSRI与TCA治疗抑郁症出现失眠、激越差异有显著性(16%和3.8%,OR=5.05,95%CI:4.06~6.30,χ2=181.7,P0.01;8.7%和3.5%,OR=2.80,95%CI:1.82~4.76,χ2=5.09,P0.01),但是焦虑、躁狂发作的差异无显著性(10.7%和8.9%,OR=1.75,95%CI:0.99~3.10,χ2=2.39,P0.05;2.2%和3.8%,OR=1.68,95%CI:0.90~3.13,χ2=1.90,P0.05)。结论在治疗抑郁症中,SSRI比TCA更可引发失眠、激越,应特别加以关注。
[本文引用:1]
|
