A Randomised, Controlled Trial to Investigate the Effect of an Intensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.

Schizophrenia, bipolar and major depressive disorders collectively affect over 10 million people across the EU and are associated with annual healthcare and societal costs in excess of 100 billion Euros. When diagnosed with one of these disorders, patients are prescribed psychotropic medication such as antidepressants, mood stabilisers or antipsychotics. It is unknown whether this first-line treatment will be successful. After this first-line treatment fails, usually a second-line treatment is initiated, and when this is not successful either a third-line treatment is initiated. Third-line treatments are quite successful, especially when compared to second-line treatments. The research question is whether the third-line treatments (early-intensified treatments) would be more efficacious than the current second-line treatments (treatment as usual) for schizophrenia, bipolar and major depressive disorders. If this is indeed the case, this could lead to the prevention of unnecessary trials of ineffective treatments and adaptations of worldwide guidelines as well as a reduction of healthcare and societal costs.

开始日期2024-09-30

申办/合作机构

University Medical Center of Utrecht

[+1]

NCT06433635 / Not yet recruiting临床4期IIT

Sequential Multiple Assignment Randomized Trial for Bipolar Depression

This is a sequential multiple assignment randomized trial for adults (ages > 18) with a bipolar disorder type 1 diagnosis currently experiencing a depressive episode. It is a randomized pragmatic trial that will compare four commonly prescribed treatments for bipolar depression, which includes three FDA-approved medications (Cariprazine, Quetiapine and Lurasidone) and one antipsychotic/antidepressant combination (Aripiprazole/Escitalopram).

开始日期2024-09-01

申办/合作机构

The General Hospital Corp.

[+1]

NCT06546358 / Not yet recruiting早期临床1期IIT

A Pilot, Double-blind, Randomized Trial of Quetiapine Versus Trazadone in Women With Postpartum Depression

Postpartum depression is a serious disorder that affects approximately 17% of women who have recently given birth. Untreated postpartum depression can negatively affect the mother, the infant, and the family. Lack of sleep is common after delivery and can trigger or worsen depression in some women. Trazodone is used for sleeplessness and depression, but it has not been studied for postpartum depression. There is preliminary evidence that quetiapine, another drug used for depression and sleeplessness, may be effective for postpartum depression. We are planning a study to compare the effectiveness and side effects of quetiapine and trazodone in women with postpartum depression. The results of this study will help us carry out larger studies comparing these drugs with a placebo (a sugar pill) in postpartum depression. We expect the results of our study will improve the mental health of mothers and the well-being of their babies and make it easier for healthcare staff to select the right drug for women with postpartum depression.

开始日期2024-09-01

申办/合作机构

Lawson Health Research Institute

100 项与富马酸喹硫平相关的临床结果

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100 项与富马酸喹硫平相关的转化医学

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100 项与富马酸喹硫平相关的专利（医药）

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5,252

项与富马酸喹硫平相关的文献（医药）

2025-02-01·JOURNAL OF AFFECTIVE DISORDERS

Effect of CYP3A5*3 genotype on exposure and efficacy of quetiapine: A retrospective, cohort study

Article

作者: Liu, Shuai ; Zhou, Chunhua ; Hao, Yupei ; Yu, Jing ; Zhao, Yan ; Wang, Ziyi ; Yuan, Shizhao

BACKGROUND:

The involvement of cytochrome P450 3A5 (CYP3A5) in the metabolism of quetiapine has been proposed, though conclusive evidence is lacking. This study aimed to quantitatively assess the impact of CYP3A5 genetic variability on quetiapine exposure in a Chinese patient population.

METHODS:

Patient data were retrospectively collected from the database of the Mental Health Centre at the First Hospital of Hebei Medical University, covering the period from September 1, 2019, to July 1, 2023. The study included patients genotyped for CYP3A5 who were treated with quetiapine. Inclusion criteria for the analysis of pharmacokinetic parameters, such as serum concentrations of the drug and its metabolites, included oral administration of quetiapine, availability of information on the prescribed daily dose and concomitant medications, and the determination of steady-state blood levels at the time of sampling (after at least 3 days of continuous administration at the same dose). Exclusion criteria comprised polypharmacy with known CYP3A4 inducers or inhibitors, as well as patients with hepatic or renal insufficiency. The primary endpoint was the exposure to quetiapine and N-dealkylquetiapine, measured using dose-corrected concentrations (C/D). The secondary endpoint was the metabolism of quetiapine to N-dealkylquetiapine, assessed by the ratio of metabolite to parent drug concentrations. The third endpoint is the differences in adverse reactions, QTc intervals, and biochemical parameters among patients with different CYP3A5 genotypes.

RESULT:

Based on the inclusion and exclusion criteria, clinical data from 207 patients were ultimately included in the study. Of these, 20 patients had the CYP3A5*1/*1 genotype, 78 had the CYP3A5*1/*3 genotype, and 109 had the CYP3A5*3/*3 genotype. The CYP3A5*3 variant was found to significantly impact the metabolism of quetiapine. The C/D values for both quetiapine and N-dealkyl quetiapine were notably higher in individuals with the *3/*3 genotype compared to those with the *1/*1 and *1/*3 genotypes (P₁ < 0.001 and P₂ = 0.002, respectively). A comparison of the variability in metabolic ratios among different genotype groups revealed no significant difference (P = 0.067). However, a post hoc analysis indicated that the metabolic ratio in poor metabolizers was significantly lower than that in intermediate metabolizers (P = 0.021). The analysis of adverse reaction incidence and QTc intervals among different genotypes showed no statistically significant differences (P = 0.652, P = 0.486). However, comparison of biochemical parameters across different genotype groups revealed that alanine aminotransferase, uric acid, hemoglobin, and gamma-glutamyl transferase levels were significantly higher in patients with the CYP3A5*3/*3 genotype compared to those with the CYP3A5*1/*1 and CYP3A5*1/*3 genotypes.

CONCLUSION:

The results indicated that the genetic polymorphism of CYP3A5*3 significantly influences the metabolism of quetiapine. Specifically, carriers of the CYP3A5*3/*3 genotype exhibited higher blood levels of quetiapine, with a greater likelihood of these levels exceeding the therapeutic range. This finding underscores the need for clinicians to pay special attention to the efficacy and occurrence of adverse reactions when prescribing quetiapine to patients carrying the CYP3A5*3/*3 genotype.

2025-01-01·ARCHIVES OF GERONTOLOGY AND GERIATRICS

Prevalence of strong anticholinergic use in residents with and without cognitive impairment and frailty: Analysis from 106 nursing homes in 12 Asia-Pacific and European countries

Article

作者: Visvanathan, Renuka ; Aalto, Ulla ; Martínez-Velilla, Nicolás ; Liau, Shin J ; Ll, Li ; Roitto, Hanna M ; Onder, Graziano ; Zhang, Tiange G ; Saarela, Riitta ; Li, Li ; Gutiérrez-Valencia, Marta ; Cross, Amanda J ; Bell, J Simon ; Zhao, Meng ; Roncal-Belzunce, Victoria ; Petrie, Kate ; Dowd, Laura A ; Jadczak, Agathe D ; Hamada, Shota ; Ooi, Choon Ean ; Liperoti, Rosa ; Pitkälä, Kaisu ; Villani, Emanuele R ; Sakata, Nobuo

PURPOSE:

There is a need to balance the benefits and risks associated with strong anticholinergic medications in older adults, particularly among those with frailty and cognitive impairment. This study explored the international prevalence of strong anticholinergic medication use in residents of nursing homes with and without cognitive impairment and frailty.

METHODS:

Secondary, cross-sectional analyses of data from 5,800 residents of 106 nursing homes in Australia, China, Czech Republic, England, Finland, France, Germany, Israel, Italy, Japan, Netherlands, and Spain were conducted. Strong anticholinergic medications were defined as medications with a score of 2 or 3 on the Anticholinergic Cognitive Burden scale. Dementia or cognitive impairment was defined as a documented diagnosis or using a validated scale. Frailty was defined using the FRAIL-NH scale as 0-2 (non-frail), 3-6 (frail) and 7-14 (most-frail). Data were analyzed using descriptive statistics.

RESULTS:

Overall, 17.4 % (n = 1010) residents used ≥1 strong anticholinergic medication, ranging from 1.3 % (n = 2) in China to 27.1 % (n = 147) in Italy. The most prevalent strong anticholinergics were quetiapine (n = 290, 5.0 % of all residents), olanzapine (132, 2.3 %), carbamazepine (102, 1.8 %), paroxetine (88, 1.5 %) and amitriptyline (87, 1.5 %). Prevalence was higher among residents with cognitive impairment (n = 602, 17.9 %) compared to those without (n = 408, 16.8 %), and among residents who were most frail (n = 553, 17.9 %) compared to those who were frail (n = 286, 16.5 %) or non-frail (n = 171, 17.5 %).

CONCLUSIONS:

One in six residents who were most frail and living with cognitive impairment used a strong anticholinergic. However, there was a 20-fold variation in prevalence across the 12 countries. Targeted deprescribing interventions may reduce potentially avoidable medication-harm.

2025-01-01·TALANTA

Fabrication of a molecularly imprinted polymer-based electrochemical sensor for the selective assay of antipsychotic drug clozapine and performance comparison with LC-MS/MS

Article

作者: Kaya, S. Irem ; Al, Selen ; Budak, Fatma ; Kul, Aykut ; Kaya, S Irem ; Cetinkaya, Ahmet ; Sagirli, Olcay ; Ozkan, Sibel A. ; Ozkan, Sibel A

Clozapine (CLO) is an atypical antipsychotic drug indicated for the treatment of schizophrenia. The treatment effectiveness of CLO is better than that of other atypical antipsychotics, and it has the advantage of being able to determine its effectiveness by measuring its concentration in the patient's blood. Thus, sensitive, selective, and accurate determination of CLO in blood is highly significant for treatment monitoring. This study describes the design and fabrication of a molecularly imprinted polymer (MIP)-based electrochemical sensor for CLO determination. This is the first MIP-based electrochemical application in the literature for CLO determination. Employing the thermal polymerization approach, the MIP was formed on the glassy carbon electrode (GCE) using CLO as the template, trans-3-(3-Pyridyl)acrylic acid (3,3-TA) as the functional monomer, and the support of zinc oxide nanoparticles (ZnO NPs). Elaborate characterizations in terms of surface morphology and electrochemistry were performed via scanning electron microscopy (SEM), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) methods. An indirect approach was employed to determine CLO in standard solution, real human biological samples, and tablet formulation, using 5 × 10^-3 M [Fe(CN)₆]^3-/4- solution as the redox probe. The limit of detection (LOD) values for the standard solution and serum sample were calculated as 2.9 × 10^-11 M and 6.01 × 10^-12 M, respectively. These values and recovery studies confirmed the sensor's sensitivity and feasibility. The measurements in the presence of similarly structured compounds (olanzapine and quetiapine fumarate) verified the sensor's superior selectivity. Moreover, the developed sensor's performance was compared and verified using an LC-MS/MS method using the student's t-test and F-test.

170

项与富马酸喹硫平相关的新闻（医药）

2024-10-25

·奇点网

改善认知看来不是抗精神病药物的长项。

*仅供医学专业人士阅读参考认知功能缺陷是精神分裂症谱系障碍（SSDs）的重要症状之一，涵盖注意力、专注力、记忆等多个方面，对疾病进程和患者生活质量有着深远影响。作为SSDs患者的关键治疗手段，抗精神病药物虽然不是专门用于改善认知功能的药物，但由于其受体结合特性，被认为可能对认知功能产生不同程度的影响。然而结果有些差强人意。德国慕尼黑工业大学的Stefan Leucht团队完成了迄今为止最全面的关于抗精神病药物与精神分裂症谱系障碍（SSDs）患者认知功能关系的网络荟萃分析，结果于近日发表在《JAMA·精神病学》期刊上。他们基于包含近千名SSD患者的68项试验数据进行分析后发现，抗精神病药物整体上对认知功能有轻微的改善效果，略胜于安慰剂，但不具有统计学意义。每种药物之间的效果差异不大，其中氯氮平、氟哌啶醇、氟奋乃静在认知功能的改善方面表现垫底，逊色于安慰剂。研究者们表示，抗精神病药物对认知功能的轻微改善可能更多是由于其减少了思维紊乱和其它阳性症状（比如激动、妄想、幻觉等），而非直接作用于认知功能本身。论文首页截图在这项研究中，Stefan Leucht等人通过系统回顾和随机效应网络荟萃分析，评估了抗精神病药物对精神分裂症谱系障碍（SSDs）患者认知功能的影响。研究的主要数据来源于Cochrane精神分裂症组试验注册库，截至2023年6月25日，共筛选并纳入68项随机对照试验，涉及9525名SSDs患者。这些患者的平均年龄为35.1岁，男性占70%。研究的主要结局是患者整体认知功能的变化，次要结局是患者具体认知领域（如处理速度、工作记忆、语言学习等）、生活质量和社会功能的变化。结果显示，整体上，抗精神病药物对认知功能的改善效果有限，虽然相比安慰剂表现出一定的优势，但效应值（SMD）较小，并且不同药物之间的差异不明显。具体来说，在改善认知的效果上，吗茚酮（Molindone，MOL）和盐酸硫利达嗪（Thioridazine，THIOR）分别排名第一和第二。不过这两种药物的分析结果都是基于单项小规模研究（15-22人数），且仅改善大脑处理速度这一个认知领域。同样，位列第五的氯丙嗪（Chlorpromazine，CPZ）也存在这个问题，但尽管相关研究数量多了些，总参与人数依然较少（N=101），且数据来源于二十世纪六七十年代的随机临床试验。相比之下，位列第三、第四的帕利哌酮（Paliperidone，PAL）和舍吲哚（Sertindole，SER），其分析结果基于近年来的研究数据，与安慰剂相比，表现出中等效果（SMD -0.43，95%CI -0.93至0.08 ；SMD -0.57，95%CI -1.03至 -0.11）。排名倒数的三位，则是氟奋乃静（Fluphenazine，FLU）（SMD = 0.15, 95% CI = -0.39至0.69）、氟哌啶醇（Haloperidol，HAL）（SMD 0.04，95%CI -0.25至0.33）、氯氮平（Clozapine，CLZ）（SMD 0.12，95%CI -0.23至0.48），落后于安慰剂。这一结果与它们的强效多巴胺型受体阻断作用相符。其他排名靠前的药物还有喹硫平（Quetiapine，QUE）、布瑞吡唑（Brexpiprazole，BRE）、利培酮（Risperidone，RIS）、唑吡坦（Zotepine，ZOT）、奥氮平（Olanzapine，OLA）、氨磺必利（Amisulpride，AMI）、鲁拉西酮（Lurasidone，LUR）、阿立哌唑（Aripiprazole，ARI）、齐拉西酮（Ziprasidone，ZIP）。排名（PLB-安慰剂）在额外的探索性事后分析中，研究按照抗精神病药物的结合受体将其分为四个组。结果显示，作用于肾上腺素能受体、5-羟色胺能药物、毒蕈碱型受体、多巴胺受体的四组药物，相比于安慰剂对患者认知功能都有改善的趋势。按作用受体分类时，每组抗精神病药物都有点小优但不明显某些药物在个别领域表现出较为积极的效果，比如刚才提到的吗茚酮和盐酸硫利达嗪对于SSD患者大脑处理速度的提高。相比于安慰剂，布瑞吡唑在视觉学习方面显示出小幅但显著的积极效果，帕利哌酮在语言学习和工作记忆方面有改善的趋势。研究还评估了患者的生活质量和社会功能，然而整体来看抗精神病药物在这些方面的表现同样有限，未能显著优于安慰剂，而且纳入分析的各项研究中认知评估工具所提供的证据也不明确。药物对具体认知功能的改善效果过去相关的荟萃分析和网络荟萃分析存在时效性不足、新药物的纳入有限、方法学质量较低等限制，并缺乏对抗精神病药物与安慰剂的直接比较。这项研究迄今为止最大的相关领域研究，表明尽管某些药物显示出小幅认知改善，但大多数抗精神病药物的效应较小，且部分药物的结果因样本小而不具备足够的意义，很难区分这些改善是否源于减少思维紊乱等症状。这些结果为临床实践中抗精神病药物的选择提供了有价值的最新见解，同时也强调了统一认知评估标准的重要性，以便未来研究能够更有效地比较不同药物的效果。另外，研究者们呼吁开发新的抗精神病药物，特别是那些针对认知缺陷的新型机制药物，以更好地满足SSDs患者的治疗需求。参考文献：[1]https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2825154本文作者丨张艾迪

临床研究

2024-10-21

·奇点网

《细胞》子刊：压力大就拉肚子，原因在这！中国科学家发现压力导致腹泻型肠易激综合征新机制丨科学大发现

*仅供医学专业人士阅读参考以前有个朋友，肠胃特别脆弱，换环境动辄水土不服，遇到什么事儿就很容易拉肚子。后来我学到肠易激综合征（IBS），感觉他可能有这个问题。 IBS的症状有很多种，比如肠道痉挛、慢性疼痛、腹胀、腹泻/便秘等等。腹泻型IBS（IBS-D）算得上非常常见。IBS-D发作与肠道感染、饮食、年龄等多种因素有关，神经/心理压力也是IBS-D发病的重要原因。压力和肠道，估计咱们的读者也能一下说出肠脑轴的存在；此外，压力也会激活下丘脑-垂体-肾上腺素（HPA）这条通路，通过神经递质导致肠道超敏反应。近期，中山大学附属第三医院靳津、东南大学李异媛团队在《细胞·代谢》杂志发文，指出了第三条IBS-D发作的关键机制通路。研究者们发现，压力会促使CD4+T细胞产生大量黄嘌呤，增加肠道中的鼠乳杆菌（Lactobacillus murinus）产生的亚精胺。亚精胺会抑制树突状细胞中1型干扰素（IFN-α）的表达，减少结肠平滑肌细胞收缩，导致排便增加。乳杆菌是一种益生菌，但这项研究指出L. murinus在IBS-D发作中扮演着重要角色，将其作为抗生素治疗的目标或许是有帮助的。同样，从饮食角度避免有利于L. murinus的食物也有改善IBS-D的潜力。论文题图早有研究认为心理因素与IBS之间存在因果关联。临床研究数据显示，IBS-D患者出现焦虑和抑郁障碍的风险更高，创伤性应激障碍患者也常见IBS-D。传统观点认为，肠脑轴的神经关联直接参与了IBS的发生，放大了疼痛信号和肠道对刺激的敏感性；此外HPA轴导致去甲肾上腺素和皮质醇释放增加，二者通过交感神经活动增加了肠道的超敏反应。研究者们在此前的工作中发现了第三条可能的机制：慢性应激可以引导CD4+T细胞过量产生黄嘌呤（Xan），黄嘌呤会积累在杏仁核和过度激活的少突胶质细胞中，导致焦虑症状。巧合的是，另一项研究发现，次黄嘌呤的消耗与IBS发病密切相关。两相结合，黄嘌呤在IBS中的作用就令人生疑了起来。研究者给小鼠腹腔注射了黄嘌呤，发现这能显著导致小鼠的内脏敏感性和粪便含水量增加，小鼠粪便排出增加，出现了明显的IBS-D样症状。黄嘌呤会导致小鼠的直肠扩张和排便增加单细胞RNA测序结果显示，黄嘌呤会影响小鼠结肠平滑肌细胞收缩相关基因和1型干扰素相关通路基因的表达。同时，免疫组化结果也显示，压力+黄嘌呤诱导的IBS小鼠结肠中IFN-α显著减少。IFN-α能够直接影响平滑肌细胞收缩，看来就是它了。经过分析，结肠中IFN-α主要来自一组浆细胞样树突状细胞（pDC），压力和黄嘌呤都会抑制pDC中IFN-α的表达。但是IFN-α又和黄嘌呤有什么关系呢？结合此前关于IBS-D患者肠菌紊乱的结论，研究者将怀疑的目光放到了肠道微生物身上。在使用头孢西丁、庆大霉素、甲硝唑、万古霉素混合抗生素治疗后，无论是压力应激还是黄嘌呤都不会再导致小鼠的内脏敏感性增加了。看来肠菌里的确是有奥妙。经鉴定，在多种IBS模式小鼠中都发现了鼠乳杆菌（L. murinus）的上调，压力应激或黄嘌呤能够明显促进鼠乳杆菌的繁殖，而鼠乳杆菌也可以诱导小鼠的IBS相关症状。鼠乳杆菌会导致小鼠内脏敏感性增加进一步分析发现，鼠乳杆菌的代谢物亚精胺是导致IBS症状的直接原因。当抑制了鼠乳杆菌中合成亚精胺的相关酶，鼠乳杆菌就不再能够诱导IBS症状了。总结一下，压力导致CD4+T细胞过量产生黄嘌呤，黄嘌呤使得鼠乳杆菌产生更多亚精胺，亚精胺则作用于pDC，抑制了其IFN-α的表达，最终影响了结肠平滑肌的运动。有趣的是，此前有一项临床研究发现，乳杆菌敏感的利福昔明，能够有效治疗IBS-D患者，与这项研究的发现形成了相互印证。这意味着在IBS治疗中，抗生素的选择需要多加考虑。L. murinus一般被认为是一种益生菌，但在IBS的情况下，它也可以成为有重要价值的治疗靶点。奇点糕近期推出了《2024ASCO年会深度盘点》课程，为大家系统盘点了2024ASCO年会上实体瘤领域的重磅进展，让您在100分钟内迅速深入把握前沿。长按识别下图中的二维码即可购买，购买后您可以在「奇点网小程序」收听，或下载奇点网「医学奇点」苹果客户端收听。如果遇到任何技术问题大家可以戳我们下图中的客服小伙伴来解决~~ 参考资料： [1]https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00366-8 本文作者 | 代丝雨

2024-10-14

·药通社

又一个首仿ANDA！！！

“天下武功，唯快不破”，这在当下极度内卷的仿制药立项上体现得淋漓尽致！目前大多数CXO和药企立项都有这么几个优选标准： 1、适应症范围广，市场容量大，有增长潜力； 2、收载于诊疗指南和临床路径，临床安全性有效性数据扎实，临床价值或定位明确； 3、贴合企业自身的市场优势领域； 4、原料药和辅料可及； 5、专利风险小； 6、现有产线尽可能匹配或稍作改造即可； 7、公开的信息和私下打听到的竞争家数少； 8、参比制剂明确，研发难度和投入小或适中； 9、临床只需要做BE/BA或者无需临床的项目，更是多数企业的心头好。舍曲林：两种盐型，三种剂型国庆节前药审中心就承办了这么一款首仿药：盐酸舍曲林口服浓缩液，受理号：CYHS2403263。该品种基本上就符合上述企业立项优选的大多数标准，相信有不少企业也立了项，但很可惜还是比海南斯达制药慢了些。舍曲林最早是由辉瑞公司研发的抗抑郁药物，属于一款经典的选择性5-羟色胺再摄取抑制剂(SSRI)，在国内企业20年前神奇的运作之下，已经有两种盐型，三种剂型，四个品种纳入了医保目录。【盐酸舍曲林片】相信大家对盐酸舍曲林片都很熟悉，1990年首次在英国上市，1991年美国上市。在抗抑郁药物中，有一种常见的药物——“左洛复”。左洛复的英文商品名为“Zoloft”，又名“舍曲林”，在临床中称为“盐酸舍曲林”，是美国处方量最大的抗抑郁品牌药。在我国临床中，左洛复除了被广泛用于治疗抑郁症、焦虑症、强迫症和双相情感障碍的治疗中，还常用于治疗创伤后应激障碍(PTSD)、重度抑郁症(MDD)、恐慌症、强迫症(OCD)、经前焦虑障碍(PMDD)和社交恐惧症等精神心理疾病。盐酸舍曲林片也早在4年前已经纳入第三批集采，也是目前临床使用最为广泛的剂型。【枸橼酸舍曲林片】哈尔滨健迪医药2001年按照改盐和改剂型申请新药临床，2006年申请生产，2008年批准上市，上市后十年终于进入国家医保(2017版至今)。舍曲林能够通过改盐上市成为独家品种，该盐基需要明显的临床优势。按照现行法规要求，笔者认为很难说服CDE。【盐酸舍曲林胶囊】原研除了片剂外，为满足高剂量使用需求，通过一项与片剂的PK对比研究和一项食物影响研究，于2021年美国上市了硬胶囊剂型。中国早在十几年前就有5家企业通过改变剂型（不改变给药途径，老5类）申请了上市。目前仅联环药业和四川百草通过了一致性评价。盐酸舍曲林胶囊目前竞争格局还是很温和的，是不是可以考虑立项？但是要注意：为什么CNS头部玩家京新药业不急着过评值得思考？【盐酸舍曲林分散片】最早也是哈尔滨健迪医药通过该剂型申报的，目前仅两家有分散片的批文，本身该品种原研并无分散片剂型，京新已经对照片剂剂型进行了两次BE试验，预计是要尝试申报一致性评价，但笔者认为批准的可能性存疑。【盐酸舍曲林口服浓缩液】该剂型是远早于胶囊剂上市的，上个世纪就批准了，该品种同样是通过一项与片剂的PK对比研究和一项食物影响研究。在其一项BA研究中，比较了100 mg舍曲林口服溶液与100 mg片剂在16名健康成人体内的药代动力学，Cmax的90%置信区间上限为126.4%，严格意义是不等效！与食物一起服用会导致Cmax和AUC的小幅增加。FDA审评认为其口服溶液与片剂的药代参数差异基本上没有临床意义！立项：可从剂型上做文章同一品种不同剂型，尤其还是那种同给药途径的项目——因为改变给药途径，基本都要做临床，前几个月讨论比较多的乙酰半胱氨酸注射液就是典型。相关文章： 1个月被CDE拒批5次？规格&适应症都不太可能批准！又2家被毙！乙酰半胱氨酸口服溶液全军覆没？给了一个立项的思路：一般该类型立项思路主要集中在神经精神类、呼吸系统和自身免疫类领域项目，比如由布瑞哌唑片扩展到布瑞哌唑片口溶膜和布瑞哌唑片口崩片；富马酸喹硫平片扩展到富马酸喹硫平缓释片，孟鲁司特钠片扩展到孟鲁司特钠颗粒、孟鲁司特钠咀嚼片、孟鲁司特钠口崩片；比拉斯汀片扩展到比拉斯汀口服溶液和比拉斯汀口崩片；依巴斯汀片扩展到依巴斯口服溶液等等。如果企业已经有了或者立项了一个剂型，与其在绞尽脑汁地寻找其他品种，不如将现有品种吃透。回归到这次申报的盐酸舍曲林口服浓缩液，就是一个典型案例。一个已经上市了二十多年的老药，且相同给药途径的药物早早在国内上市，可以豁免生物等效性研究的假3类项目，然而申报企业是海南斯达制药，但其并没有上市的舍曲林相关制剂。按理说，京新药业，本身就有舍曲林的片剂、胶囊和分散片的批准文号，本能就应该对舍曲林是否存在其他剂型比其他企业有天生的敏感度才对，抛开市场不谈，京新药业作为盐酸舍曲林口服浓缩液的首仿才是最合理，也是最容易的。 PS: 立项还可以从哪些方面去考量，去寻找新项目，后续咱们慢慢聊，欢迎留言。投稿/内容沟通：华籍美人（Ww_150525）近期精华文章

上市批准专利到期一致性评价

100 项与富马酸喹硫平相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00458	富马酸喹硫平	N05AH04	DB01224

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
双相情感障碍及相关疾病	日本	Kyowa Pharmaceutical Industry Co., Ltd.	2017-07-03
躁郁症1型	美国	Intellipharmaceutics International, Inc.	2017-05-09
躁郁症1型	美国	法德生技药品股份有限公司	2017-05-09
躁郁症1型	美国	Endo Operations Ltd.	2017-05-09
躁郁症2型	美国	Endo Operations Ltd.	2017-05-09
躁郁症2型	美国	法德生技药品股份有限公司	2017-05-09
重度抑郁症	美国	AstraZeneca UK Ltd.	2009-12-02
躁郁症	美国	AstraZeneca Pharmaceuticals LP	1997-09-26
精神分裂症	美国	AstraZeneca Pharmaceuticals LP	1997-09-26

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
大麻滥用	临床3期	德国	AstraZeneca PLC	2009-09-01
难治性抑郁症	临床3期	澳大利亚	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	奥地利	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	比利时	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	保加利亚	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	丹麦	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	德国	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	匈牙利	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	意大利	AstraZeneca PLC	2008-11-01
难治性抑郁症	临床3期	葡萄牙	AstraZeneca PLC	2008-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01858948 (CTgov)	临床3期	代谢综合征 \| 躁郁症	19	Placebo+Quetiapine fumarate	淵觸壓鏇蓋淵餘鏇淵繭(壓鑰齋築觸簾鏇窪積夢) = 選構壓窪衊壓淵夢鏇衊製簾繭艱積鹽遞範醖鑰 (餘醖糧壓觸築糧獵選淵, 簾鬱築願廠願憲觸範獵 ~ 範淵遞願網壓鬱願顧積) 更多	-	2022-11-25
NCT02845453 (CTgov)	临床4期	躁郁症 \| 物质滥用	24	Quetiapine (Quetiapine)	醖膚淵窪鹽積鏇網鹹觸(繭鬱醖壓鑰壓齋簾齋夢) = 繭糧製糧廠壓蓋獵顧糧製鹽範鬱憲積餘構艱製 (積鹽壓簾醖蓋鬱築簾廠, 鏇淵積衊衊範遞夢構艱 ~ 艱製範襯糧顧鬱顧醖糧) 更多	-	2022-04-18
				Placebo (Placebo)	醖膚淵窪鹽積鏇網鹹觸(繭鬱醖壓鑰壓齋簾齋夢) = 遞醖醖醖淵願觸餘鹽窪製鹽範鬱憲積餘構艱製 (積鹽壓簾醖蓋鬱築簾廠, 顧觸憲醖顧簾簾餘夢糧 ~ 窪廠膚遞醖製遞鬱積餘) 更多
NCT00688818 (Pubmed)	N/A	抑郁症 \| 焦虑症追加	76	Quetiapine XR	衊壓艱壓醖糧醖遞簾製(選壓鬱糧簾獵獵衊襯顧) = 積鹽鏇膚糧繭顧網範糧蓋繭鏇願繭製醖網膚蓋 (憲觸憲鑰鏇簾範衊鏇膚, -7.41 ~ -0.64) 更多	积极	2022-03-21
NCT03568500 (CTgov)	临床4期	分裂情感性障碍 \| 精神分裂症	44	Digital Medicine System+Aripiprazole (Aripiprazole)	簾窪鏇願鬱繭夢構網獵(衊蓋觸繭範鬱憲糧鹽選) = 觸淵淵糧鑰淵蓋鬱簾壓繭憲製窪鹹鹹鹽網衊糧 (選簾廠廠觸膚齋積簾獵, 夢壓壓積觸繭觸積蓋範 ~ 繭簾齋願繭齋觸鏇糧餘) 更多	-	2020-07-16
				Digital Medicine System+Olanzapine (Olanzapine)	簾窪鏇願鬱繭夢構網獵(衊蓋觸繭範鬱憲糧鹽選) = 選網齋窪範觸簾鹹製觸繭憲製窪鹹鹹鹽網衊糧 (選簾廠廠觸膚齋積簾獵, 餘壓範鹽繭蓋廠膚範鬱 ~ 淵襯選範膚構廠齋齋構) 更多
NCT00579280 (CTgov)	临床4期	躁郁症 \| 恐慌 \| 惊恐障碍 ... 更多	224	quetiapine SR (Quetiapine SR)	膚鑰繭選壓鹹憲衊膚築(鏇醖鑰壓簾顧遞壓窪顧) = 壓顧膚餘簾遞顧簾壓蓋齋積選醖蓋積築鹹獵餘 (鹹蓋鑰範艱衊範窪積顧, 淵構築襯範蓋積醖衊鬱 ~ 窪鹽範齋壓遞選積醖繭) 更多	-	2020-06-11
				divalproex sodium ER (Divalproex Sodium ER)	膚鑰繭選壓鹹憲衊膚築(鏇醖鑰壓簾顧遞壓窪顧) = 鏇廠襯膚壓製繭衊鹹繭齋積選醖蓋積築鹹獵餘 (鹹蓋鑰範艱衊範窪積顧, 製膚壓餘壓壓選醖齋願 ~ 艱構鹽壓鬱積夢鏇積繭) 更多
NCT01725308 (Pubmed)	临床2/3期	躁郁症	322	Quetiapine XR 150 mg	獵觸衊遞繭遞築窪願築(餘構築鬱繭網願製廠鹽) = 鹽窪艱簾築選鹽選選淵夢蓋簾艱遞鬱衊壓壓衊 (簾積顧醖繭糧醖簾廠廠 )	-	2020-06-06
				Quetiapine XR 300 mg	獵觸衊遞繭遞築窪願築(餘構築鬱繭網願製廠鹽) = 繭鹽齋範鏇膚積獵築淵夢蓋簾艱遞鬱衊壓壓衊 (簾積顧醖繭糧醖簾廠廠 )
NCT01119014 (TEA, Pubmed \| J Am Acad Child Adolesc Psychiatry)	临床4期	精神障碍	113	Quetiapine-Extended Release	憲衊鬱廠選蓋鬱鹹範鏇(鬱願襯鑰蓋蓋製鏇遞範) = 廠簾獵餘廠願觸襯糧簾廠醖淵壓顧窪鹽網齋膚 (壓廠獵醖簾艱衊簾網獵, 3.92 ~ 5.83)	不佳	2019-11-01
				Aripiprazole	憲衊鬱廠選蓋鬱鹹範鏇(鬱願襯鑰蓋蓋製鏇遞範) = 選鏇淵憲選鏇構壓壓選廠醖淵壓顧窪鹽網齋膚 (壓廠獵醖簾艱衊簾網獵, 0.97 ~ 2.97)
NCT00515723 (Glulipid, CTgov)	N/A	2型糖尿病 \| 分裂情感性障碍 \| 精神分裂症 ... 更多	96	olanzapine (Olanzapine)	網獵憲窪艱鹹餘製積餘(繭網願觸繭醖範壓窪壓) = 築廠繭遞窪餘鏇鹹餘鬱廠鑰顧網範構構遞獵糧 (鑰壓糧餘遞夢鏇蓋襯窪, 襯蓋願製壓繭構襯鬱築 ~ 鹹鏇醖膚願製鑰鑰選醖) 更多	-	2019-10-02
				risperidone (Risperidone)	網獵憲窪艱鹹餘製積餘(繭網願觸繭醖範壓窪壓) = 鹽顧醖淵繭憲觸築艱衊廠鑰顧網範構構遞獵糧 (鑰壓糧餘遞夢鏇蓋襯窪, 壓選餘築襯鹹餘鏇簾膚 ~ 觸範廠鑰鹽襯鬱襯窪構) 更多
NCT00269399 (CTgov)	临床3期	艰难梭菌腹泻 \| 腹泻 \| 梭菌感染	237	Rifaximin (Xifaxan) (Rifaximin Treatment Arm)	鑰淵鏇鬱遞觸鑰顧憲糧(壓襯網積繭構衊網鹹壓) = 淵選餘艱製簾積構壓夢齋醖鑰壓蓋夢鏇醖衊遞 (鏇襯鬱淵鏇齋積艱簾製, 憲膚憲餘憲蓋製製鬱積 ~ 遞築窪艱艱顧鑰襯壓齋) 更多	-	2019-10-01
				Vancomycin (Vancomycin Comparator Arm)	鑰淵鏇鬱遞觸鑰顧憲糧(壓襯網積繭構衊網鹹壓) = 襯構醖壓壓淵獵願壓糧齋醖鑰壓蓋夢鏇醖衊遞 (鏇襯鬱淵鏇齋積艱簾製, 觸衊鹽顧糧鬱齋淵窪簾 ~ 繭鹹壓選襯繭鹽顧膚鑰) 更多
NCT00518973 (CTgov)	N/A	神经性厌食症	21	Placebo (Placebo)	衊積願鑰廠齋鑰鏇築顧(鬱醖鏇廠積衊積蓋醖鹽) = 餘鏇衊製顧醖憲餘壓簾鹽製鹹襯網顧觸鏇築製 (製醖膚製壓鬱繭遞觸鑰, 壓餘糧鬱鹹範餘淵鏇壓 ~ 鹹獵顧鏇膚顧鑰蓋獵襯) 更多	-	2019-07-17
				Quetiapine (Quetiapine)	衊積願鑰廠齋鑰鏇築顧(鬱醖鏇廠積衊積蓋醖鹽) = 鏇觸蓋獵淵膚廠夢築鏇鹽製鹹襯網顧觸鏇築製 (製醖膚製壓鬱繭遞觸鑰, 範衊製鹽鏇壓襯鏇觸構 ~ 艱艱醖繭築願製鹹窪廠) 更多