Prochlorperazine

开篇引入 在全球医学与药学高速发展的今天，药师的临床角色不断提升。药师不仅需要懂药，更需要理解疾病诊疗的整体思路，才能在多学科团队中真正发挥价值。 然而现实中，中国药师在临床教育和实践的衔接上仍存在不足： 缺乏系统的疾病诊治思维训练，难以在临床工作中有效参与和对话。 为此，北京药师协会和京健会联袂策划了全新专栏 —— ✨ 《药学前沿 · 国际视野》 ✨ 🎯  为什么要办这个专栏？ •补短板：帮助药师快速理解常见疾病的诊断与治疗路径，形成完整临床思维。 •看前沿：聚焦国际最新研究成果与循证指南，第一时间传递学术热点。 •重实践：将国际进展转化为药学服务可操作的工具与路径。 •促成长：打造药师持续学习与交流的平台，加速专业能力提升。 📚  专栏亮点 ✨ 覆盖领域广 糖尿病、心血管、消化系统、感染、肿瘤、免疫、神经精神、皮肤科、女性健康……全面梳理！ ✨ 内容形式多样 •前沿综述：系统总结最新循证与研究进展 •临床解读：聚焦诊疗路径与药师切入点 •案例分享：从实践出发，转化为日常经验 •互动沙龙：定期线上讨论，促进学术交流 ✨ 实用导向强 聚焦“能用、好用”，帮助药师在临床中真正落地。 👥  编辑团队 •专家顾问：国内外知名学者定期指导，确保权威与国际视野 •学术统筹：北京药师协会副理事长及学术交流工作组 •领域编辑：内分泌、心血管、感染、肿瘤、免疫、精神神经、皮肤、女性健康等领域临床药师 •青年药师组：负责文献搜集、病例整理、实践转化 🤝  互动邀请 我们诚挚邀请各位药师朋友： 📌 关注专栏，第一时间掌握国际前沿动态 📌 分享经验，让更多同行从中获益 📌 提出建议，推动专栏不断优化 👉 未来，北京药师协会还将根据大家的反馈，定期组织线上学术交流活动，共同探讨药学发展的新路径。 第七期 《女性健康和皮肤护理简报》 本期编者： 南京江宁莱宁门诊部 胡艳鹏  专家点评如下： 本期目录: （一）产后抑郁症的病理机制以及Zuranolone，FDA批准用于治疗该疾病的首款药物； （二）Elinzanetant，一种针对绝经期血管舒缩症状的新型药物； （三）子宫切除术和卵巢切除术与中风之间的联系； （四）阴道微生物群作为妇科癌症、子宫内膜异位症、多囊卵巢综合征、生育障碍、妊娠并发症和绝经期症状的诊断工具； （五）妊娠恶心和呕吐症状的药物治疗； （六）绝经前特发性骨质疏松症的病理机制及治疗 点评内容 （一）产后抑郁症的病理机制以及Zuranolone，FDA批准用于治疗该疾病的首款药物 1）产后抑郁（PPD）的发病机制与佐拉诺酮（zuranolone）的作用基础 •围产期神经类固醇撤退 → GABA 受体功能失衡。 妊娠晚期，体内内源性神经类固醇（如别孕酮，allopregnanolone）水平显著升高，这些物质是 GABA_A 受体的强效正向变构调节剂。分娩后其水平骤降，导致 抑制性神经传导不足、边缘-前额叶环路兴奋/抑制失衡，以及下丘脑-垂体-肾上腺轴（HPA）应激调节异常。这些病理改变被认为是产后抑郁的重要生物学机制。 •佐拉诺酮是一种 合成神经类固醇，通过正向调节突触和突触外的 GABA_A 受体，恢复抑制性信号，从而快速改善症状。 2）佐拉诺酮的临床证据与作用特点 •药物与适应证。 佐拉诺酮（商品名 ZURZUVAE）是 首个口服获 FDA 批准的产后抑郁治疗药物，疗程为 14 天，每日一次。 •关键研究（III 期 RCTs）。 两项多中心、随机、双盲试验证实：HAMD-17 评分在第 15 天显著优于安慰剂，且疗效 维持至第 45 天（即停药 4 周后）。 •起效与持久性。 在第 3–15 天即可见效，但长期数据（>45 天）有限，因此后续维持治疗需另行考虑（如合并抗抑郁药）。 3）给药方式与安全要点（FDA 标签） •推荐剂量。 晚餐后（需含 400–1000 千卡、25–50% 脂肪）口服 50 mg，每日一次，连用 14 天。若出现中枢抑制症状，可减至 40 mg。可 单用或合并口服抗抑郁药（SSRI/SNRI）。 •特殊人群与药物相互作用: •CYP3A4 强抑制剂：降至 30 mg/日；CYP3A4 强诱导剂禁用。 •肾功能不全（eGFR <60）或重度肝功能损害（Child-Pugh C）：30 mg/日。 •主要警告: •驾驶与警觉性受损：每次服药后 ≥12 小时禁止驾驶或操作危险机械。 •与酒精、苯二氮卓类、阿片类、三环类抗抑郁药等并用时中枢抑制作用叠加。 •妊娠与避孕。 存在潜在胎儿风险；治疗期间及停药后 1 周内需避孕。 •哺乳期。乳汁转移量极低（婴儿相对剂量 RID <1%）；ACOG 建议个体化决策，可继续哺乳、暂停或泵奶丢弃（疗程及停药后 1 周）。 •管制属性。属于 C-IV 类管制药物，滥用潜力接近阿普唑仑。 4）指南及专家共识中的定位 •ACOG 实践建议（2024 年 1 月更新） •建议在 分娩后 12 个月内，对于 妊娠三期或产后 4 周内起病的抑郁，可考虑佐拉诺酮。 •FDA 批准未区分严重程度，但临床试验多纳入 重度 PPD（HAMD-17 >26） 患者。 •使用方式：可单独或合并 SSRI/SNRI。 •哺乳期处理：根据 RID 数据和母婴需求，进行共同决策。 •AAFP 证据总结（2025）。 认为佐拉诺酮在 重度 PPD 有效（证据强度 A，基于 RCT Meta 分析）。 •英国 NICE。 正在进行技术评估，定位于 重度 PPD。 5）临床整合与决策逻辑 •适合使用佐拉诺酮的场景： •症状严重、需快速缓解（如影响母婴功能、照护能力）。 •不便住院接受 布瑞克酮（brexanolone，静脉 60h 输注）。 •需注意： •療效持久性有限 → 需配合 SSRI/SNRI 维持治疗 + 心理干预。 •轻中度 PPD 或有良好 SSRI 应答史 → 首选 SSRIs。 •存在驾驶需求、药物相互作用风险或物质滥用风险时，需谨慎选择。 6）处方前临床检查清单 1.明确起病时间（孕晚期或产后 ≤4 周），量化症状（EPDS/PHQ-9/HAMD-17）。 2.排查自杀风险、癫痫史、物质使用风险。 3.评估驾驶及日常照护安排（用药期间禁止夜间驾驶）。 4.药物相互作用检查（避免 CYP3A4 诱导剂，强抑制剂需降剂量）。 5.肾功能/肝功能评估（决定是否用 30 mg）。 6.避孕与妊娠咨询；孕期登记。 7.哺乳期决策（继续、暂停或泵奶丢弃）。 8.治疗中监测（不良反应、量表评分 Day 7–15、Day 45）。 总结： 佐拉诺酮是首个口服快速起效的 PPD 靶向治疗药物，作用机制符合产后抑郁的神经生物学特点。其临床定位主要是 中重度产后抑郁，尤其是 需快速改善功能的患者。由于长期疗效证据有限，通常建议 与 SSRIs/SNRIs 和心理治疗联合应用，同时遵循 驾驶禁令、避孕与哺乳管理、药物相互作用等安全要点。 （二）Elinzanetant，一种针对绝经期血管舒缩症状的新型药物 Elinzanetant 在更年期血管舒缩症状（VMS）中的作用机制、指南定位以及与其他药物的对比总结： 1. 发病机制与作用原理 •更年期VMS病理机制：雌激素下降 → 下丘脑KNDy神经元（Kisspeptin、Neurokinin B、Dynorphin）失衡 → •Neurokinin B（NKB）-NK3通路过度活跃 → 体温调节区热中性带变窄 → 潮热、盗汗。 •Substance P-NK1通路参与血管扩张、睡眠和情绪调节。 •Elinzanetant作用机制： •双重NK1/NK3拮抗剂，同时抑制 NKB/NK3（体温调节）和 SP/NK1（睡眠与情绪），因此不仅能缓解潮热，还可能改善睡眠障碍和情绪问题。 2. 治疗路径中的定位（指南与监管背景） •北美更年期学会（NAMS 2023）： •**雌激素±孕激素治疗（MHT）**是VMS最有效方案，推荐在风险可控人群中使用。 •对于不适合或不愿使用MHT者，推荐非激素方案，包括 SSRIs/SNRIs、加巴喷丁、可乐定； •同时认可 NK受体拮抗剂为有前景的靶向疗法，当时已有Fezolinetant获批。 •最新进展： •Elinzanetant（Lynkuet）于2025年7月8日获英国MHRA全球首批批准，适用于中重度VMS。 •在英国可作为 非激素一线治疗，尤其适合MHT禁忌或不耐受的女性。 •美国FDA仍在审评中。 临床定位总结： •首选MHT：若无禁忌且患者接受。 •非激素首选之一：MHT不适合或拒绝时，Elinzanetant可作为一线非激素治疗，尤其适合伴睡眠障碍的患者。 3. 疗效与安全性对比 (1)Elinzanetant •OASIS-1 & 2（III期，26周）：显著降低潮热频率与严重度（4周和12周起效），同时改善睡眠质量与生活质量。 •OASIS-3（长期研究）：疗效持续至52周，无子宫内膜增生信号。 •OASIS-4：在接受乳腺癌内分泌治疗的患者中同样有效。 •安全性：常见不良反应为头痛、疲劳、嗜睡；未见严重肝损伤信号。 (2)与其他药物比较 临床要点总结 •作用机制：Elinzanetant通过双重阻断NK1/NK3，同时改善潮热与睡眠，是机制上更全面的非激素疗法。 •疗效：与Fezolinetant类似，可显著降低潮热，但在睡眠改善方面优势更明显。 •安全性：无严重肝损伤警告，较Fezolinetant更具潜在安全优势；常见不良反应轻微。 •定位：在MHT禁忌或拒绝人群中，可作为一线非激素选择，尤其适合伴睡眠障碍的患者。 （三）子宫切除术和卵巢切除术与中风之间的联系 (1)最新研究发现 近期一项系统综述与Meta分析，以及基于美国NHANES（1999–2018）的队列研究，对相关风险有了新的认识。 其他发现： •分层分析显示：无论手术指征（良性/恶性）、卵巢是否保留、参考人群如何，风险升高趋势大体一致【LWW期刊】。 •在NHANES队列中，单纯子宫切除与卒中死亡并无显著关联；但综合多项研究的Meta分析确实发现卒中发生率升高。 •另一项研究（Shen R 等）分析14214例女性，调整了年龄、种族、社会经济因素、心血管健康指标、抑郁等混杂因素后发现，子宫切除（有或无卵巢切除）仍与卒中风险增加显著相关【PMC全文](https://pmc.ncbi.nlm.nih.gov/articles/PMC10233142/?utm_source=chatgpt.com)】。 (2)研究局限与不确定性 1.观察性研究为主：因果关系未被证实，残余混杂因素可能存在。 2.自我报告偏倚：部分研究依赖患者自述手术或卒中史，存在分类错误风险。 3.手术年龄：年轻时（如 <45–50岁）行卵巢切除或子宫切除，风险更高。 4.激素替代治疗（HRT）：HRT的使用与否、开始时间、方案等可能影响风险，但现有数据有限。 5.卒中类型区分不足：大多数研究未能明确区分缺血性卒中、出血性卒中或TIA。 6.随访时间不足：部分研究随访 <10年，长期影响有待进一步观察。 (3)可能的生物学机制 1.雌激素/卵巢激素缺乏：双侧卵巢切除导致性激素骤降，雌激素的血管保护作用（抗炎、抗动脉粥样硬化、改善血脂、血管舒张等）丧失。 2.过早或外科性绝经：提前绝经与高血压、血脂异常、糖耐量异常等心血管危险因素密切相关。 3.卵巢血供受损：即使保留卵巢，子宫切除术也可能损伤卵巢血流，加速卵巢功能衰退。 4.与传统危险因素叠加：接受手术的女性常合并肥胖、高血压、糖尿病等风险因素，手术可能放大其作用。 5.代谢改变：激素骤降可导致血脂不良、胰岛素抵抗、内脏脂肪增加，从而促进动脉粥样硬化。 (4)临床与实践启示 •术前告知：在决定子宫/卵巢切除时，尤其是年轻女性，应充分沟通其远期卒中及心血管风险。 •保留卵巢（若可行）：若无恶性肿瘤风险，保留卵巢可降低心血管风险。 •激素替代治疗：对年轻外科性绝经患者，HRT或有助于部分风险缓解，但仍需个体化权衡（卒中、乳腺癌、血栓等风险）。 •长期随访与风险控制：手术后女性应加强血压、血脂、血糖、体重等监测与干预。 •未来研究方向：需有更长期的前瞻性研究，明确不同卒中类型、手术年龄、HRT使用情况的具体影响。 总结 •子宫切除术本身与卒中风险有轻度升高的相关性； •双侧卵巢切除术风险更高； •子宫+双侧卵巢切除的风险最大（可达约50%升高）。 •虽然效应量相对温和（HR 1.1–1.5），但考虑到卒中在老龄女性中的高基线风险，临床意义不可忽视。 （四）阴道微生物群作为妇科癌症、子宫内膜异位症、多囊卵巢综合征、生育障碍、妊娠并发症和绝经期症状的诊断工具 阴道微生物组诊断在妇科癌症、子宫内膜异位症和腺肌症、多囊卵巢综合征、不孕不育、妊娠并发症和更年期症状 1）妇科癌症 现有证据 •宫颈/子宫内膜/卵巢：阴道微生态失调，尤其是 乳酸杆菌减少、厌氧菌（如 Gardnerella, Atopobium, Sneathia）增多，与 HPV 持续感染、宫颈上皮内瘤变及宫颈癌的发生风险密切相关。部分研究提示也可能影响子宫内膜癌和卵巢癌的炎症环境、代谢物及免疫反应。 •因果关系尚未证实，但关联性在不同研究中较为一致。 诊断意义 •乳酸杆菌不足的阴道环境 可能提示 HPV 持续存在和宫颈病变风险。当前仅作为研究级 风险分层工具，尚未进入临床指南。 2）子宫内膜异位症与腺肌症 1.现有证据 •子宫内膜异位症：研究发现患者阴道和肠道微生物组发生改变（↑ 多样性，特定菌群比例异常），但不同研究结果差异较大，因果关系尚不清楚。 •腺肌症：病例对照研究显示腺肌症患者阴道菌群组成与对照不同，并且在月经周期不同阶段差异更明显。部分研究探索通过 机器学习算法 对阴道菌群进行分类。 2.诊断意义 •目前仍属 科研探索阶段。若未来得到验证，基于阴道菌群的无创检测可能有助于 早期筛查 或 表型分型（如与疼痛、炎症相关的菌群模式），但 尚不能用于临床诊断。 3）多囊卵巢综合征（PCOS） 1.现有证据 •多项研究（2023–2024 年）提示 PCOS 患者的阴道菌群 多样性增加，且与对照人群相比存在菌群组成差异，包括病毒组/噬菌体群落的改变。但样本量较小，结果存在不一致性。 2.诊断意义 •尚不足以作为诊断或分型依据。阴道微生物组在 PCOS 中的作用仍属探索阶段，未来可能用于识别 炎症相关亚型 或感染易感性。 4）不孕与辅助生殖（ART/IVF） 1.现有证据 •多项研究发现 乳酸杆菌占优势的阴道菌群（尤其 L. crispatus） 与更好的 着床率、妊娠率和活产率 相关。 •相反，BV 或微生态失调与胚胎移植失败和流产相关。 •促排卵（COS）过程可能使部分女性的菌群转向失调。 2.诊断意义 •已有一定应用价值（辅助性）： •在 IVF 前进行阴道菌群检测（如 qPCR BV 面板），识别微生态失调并在移植前进行优化。 •检测结果可指导 BV 治疗 或 益生菌/活体生物制剂干预（在获批地区/条件下），并通过复测确认菌群恢复到乳酸杆菌优势。 •证据支持，但 尚未成为强制性指南推荐。 5）妊娠并发症 1.现有证据（最强） •早产（PTB）：多项系统评价和大型队列一致发现： •乳酸杆菌不足、厌氧菌（Gardnerella, Atopobium, Sneathia, Megasphaera, Shuttleworthia）增多，与早产风险增加相关； •L. crispatus 占优势，具有保护作用； •妊娠早期 L. iners 占优势 可能提示较高的复发性早产风险（因其容易转向失调）。 •其他并发症：有研究提示阴道菌群失调与 流产、子痫前期、绒毛膜羊膜炎、胎膜早破、妊娠期糖尿病 等相关，但结果尚不一致。 2.诊断意义 •最具应用前景的方向： •在 高危孕妇人群 中进行 早孕期阴道菌群检测和动态监测，有望用于 早产风险分层。 •对于检测结果异常者，可加强监测或进入干预性研究。 •目前尚未成为常规 人群筛查指南。 6）更年期症状（绝经相关泌尿生殖综合征，GSM） （1）现有证据 •随着雌激素水平下降：阴道上皮变薄，糖原减少，pH 升高，乳酸杆菌显著减少 → 与 阴道、性功能及泌尿症状 密切相关。 •临床研究表明 局部雌激素治疗 能恢复乳酸杆菌优势，改善症状；部分研究比较了雌激素与激光治疗对菌群的不同影响。 （2）诊断意义 •目前可作为辅助工具： •在更年期症状患者中，检测阴道菌群可用于 记录失调基线，并 监测局部雌激素或非激素治疗后的反应。 •不能单独作为诊断标准，但可增强治疗决策和随访。 （3）临床检测应用框架（现阶段） 最具现实价值的场景 1.辅助生殖/IVF 前评估 ——优化阴道微生态，提高成功率。 2.高危妊娠早产风险监测 ——早孕期检测并动态随访。 3.更年期症状管理 ——基线检测 + 治疗随访（局部雌激素或其他干预）。 （4）检测方式推荐 •首选 qPCR/BV 面板（可定量主要厌氧菌及乳酸杆菌）。 •16S/宏基因组测序 多用于科研或复杂病例。 （5）尚未成熟的应用 •妇科癌症筛查或预后判断 •PCOS 的诊断或分型 •子宫内膜异位症/腺肌症的无创检测 目前均属于研究阶段，尚未进入常规临床。 总结： 阴道微生物组诊断在 辅助生殖、妊娠并发症风险分层、更年期管理 中已初具应用价值；在 妇科肿瘤、PCOS、子宫内膜异位症/腺肌症 中仍处于探索阶段。未来结合 组学、人工智能和精准医学，有望成为妇产科个体化诊疗的重要工具。 （五）妊娠恶心和呕吐症状的药物治疗 妊娠期恶心呕吐（NVP）止吐药指南推荐 1. 总体原则 •一线处理：生活方式和饮食调整（少量多餐、避免诱因、生姜、穴位按压）。 •分步药物治疗：在确保安全性的前提下，逐步加用药物。 •目标是控制症状，预防脱水、电解质紊乱和体重下降等并发症。 2. 指南推荐的止吐药物 （1）一线药物 •吡哆醇（维生素B6） ± 多西拉敏 •ACOG：推荐为一线治疗。 •多西拉敏（H1受体拮抗剂）与吡哆醇联合制剂（Diclegis®，Xonvea®）已获 FDA 批准。 •各孕期均安全。 （2）二线药物（若一线无效） 1.抗组胺药 •苯海拉明、美克洛嗪、茶苯海明。 •有效、常用，畸形风险低。 2.多巴胺受体拮抗剂 •甲氧氯普胺（胃复安）：有效，但需警惕锥体外系反应；短期使用安全。 •吩噻嗪类（异丙嗪、丙氯拉嗪）：疗效确切，使用历史悠久。 （3）三线药物 / 难治性病例 1.5-HT3受体拮抗剂 •昂丹司琼（Ondansetron）：常用于难治性NVP。 •证据：疗效明确。 •安全性：大多数研究未见显著畸形风险，但有少数提示与口裂/心脏畸形轻度相关；仅在获益大于风险时使用。 •ACOG/RCOG 建议：在其他药物失败后考虑。 2.糖皮质激素 •甲泼尼龙、泼尼松龙可用于对常规治疗无效的妊娠剧吐。 •妊娠 <10 周时避免使用（可能增加唇裂/腭裂风险）。 3. 支持措施 •静脉补液：生理盐水 ± 钾盐。 •硫胺素补充：在输注葡萄糖前必须给予，防止 Wernicke 脑病。 •营养支持：严重、难治病例可考虑肠内/肠外营养。 4. 各国指南差异 •ACOG（美国）：分步——吡哆醇/多西拉敏 → 抗组胺/吩噻嗪/甲氧氯普胺 → 昂丹司琼 → 糖皮质激素。 •RCOG（英国）：推荐吡哆醇/多西拉敏；中重度NVP可用昂丹司琼。 •SOGC（加拿大）：因疗效确切、安全性较好，昂丹司琼在路径中使用更靠前。 •WHO：强调安全性、可及性，重症患者需补液和硫胺素。 5. 实用总结表 临床要点： •治疗流程：非药物措施 → 吡哆醇/多西拉敏 → 分步加药。 •硫胺素是妊娠剧吐长期患者在使用葡萄糖前必须补充的。 •昂丹司琼效果显著，但因部分研究提示风险，应留作难治病例。 •糖皮质激素仅用于严重、对常规治疗无效的妊娠剧吐。 （六）绝经前特发性骨质疏松症的病理机制及治疗 PIO 是一种罕见疾病，表现为绝经前女性在无继发性病因（如内分泌、营养、全身疾病、药物）的情况下出现低骨密度和脆性骨折。其病理生理尚未完全阐明，但提出了多种相互关联的机制： 1. 骨重建失衡 •正常情况：在绝经前女性中，骨代谢通常是平衡的，破骨细胞吸收与成骨细胞形成相匹配。 •在 PIO 中：出现骨重建失衡： •骨吸收正常或增加， •骨形成不足或受损。 → 结果是尽管年轻，仍出现进行性骨丢失。 2. 成骨细胞功能障碍 •研究提示 成骨细胞数量和功能受损，导致骨形成减少。 •骨钙素水平低、骨形成标志物下降。 •间充质干细胞分化异常，趋向脂肪生成而非成骨。 3. 破骨细胞活性与 RANKL/OPG 轴 •RANKL/OPG 比值异常，偏向于破骨细胞生成 → 骨吸收增加。 •部分患者骨吸收标志物升高（如血清 CTx）。 4. 胶原和骨基质异常 •骨胶原交联异常及细胞外基质质量缺陷可降低骨强度（独立于 BMD）。 •骨微结构缺陷：HR-pQCT 显示小梁变薄、连接性下降。 5. 激素与代谢因素 •雌激素水平在 PIO 中通常正常（区别于绝经后骨质疏松）。 •可能存在微妙异常： •维生素 D 代谢/受体异常， •PTH 敏感性改变， •IGF-1 信号低下。 6. 遗传易感性 •家族聚集现象与候选基因研究提示 遗传背景： •涉及 COL1A1, LRP5, WNT 信号通路, ESR1 等。 •影响胶原合成、成骨细胞活性、Wnt 信号。 7. 骨髓微环境 •骨髓脂肪增加与炎性细胞因子改变（如 IL-6, TNF-α）→ 有利于骨吸收。 8. 力学与局部因素 •机械负荷不足或 力学感受通路缺陷（如 Wnt/β-catenin, sclerostin 调控）→ 适应性骨形成受损。 总结 PIO 很可能是 异质性疾病。其发病机制包括： •成骨细胞功能障碍， •骨吸收过度或重建失衡， •骨基质微结构脆弱， •遗传和内分泌/代谢细微异常。 由于并非由雌激素缺乏驱动，PIO 与绝经后骨质疏松症存在根本区别，因此治疗策略不同（如避免过度使用单纯抗吸收药，强调促骨形成治疗）。 临床证据 1.特立帕肽在 PIO •II 期 RCT（41 例 PIO 女性，20 µg/天，24 个月）： •腰椎 BMD ↑ 约 13.2% •全髋、股骨颈 ↑ 约 5% •HR-pQCT：小梁数量↑、皮质厚度↑ •~18-20% 不应答（低骨形成率者） •延长研究：特立帕肽 24 个月 → 接 Denosumab 24 个月 → 腰椎 BMD ↑ ~22%，髋/股骨颈 ↑ ~9-10%。 2.罗莫苏单抗在 PIO •2025 年 II 期试验（29 例 PIO 女性，210 mg/月 ×12 个月 → 接 Denosumab）： •腰椎 BMD ↑ ~15% •髋/股骨颈 BMD ↑ ~5% •TBS ↑ ~3% •与历史特立帕肽队列对比：腰椎/远端桡骨 BMD 增益更大，尤其远端桡骨无下降（特立帕肽部分有下降）。 3.总结 •罗莫苏单抗：腰椎 BMD 提升更快更明显，远端桡骨无下降，疗程短（12 月），但 CV 风险需关注。 •特立帕肽：长期证据更多，微结构改善证据更充分，但应答率因骨形成水平而异，部分患者无明显反应。 •两者均需后续抗吸收药巩固。 •临床选择需结合患者基线骨代谢情况、风险因素、药物可及性与安全性。 点评专家 李达 莱佛士医疗中国区首席药师 北京大学药学院临床药学专业 研究生导师 北京药师协会副理事长 中国药理学会治疗药物监测专业委员会 常务委员 中国医促会药学信息化分会 委员 全国老年药学联盟 顾问 美国药师协会MTM（药物治疗管理）培训师 美国药师协会MTM（药物治疗管理）药师 美国药师协会Cardiovascular 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Continuous treatment with INGREZZA 40 mg for 48 weeks resulted in sustained, clinically meaningful improvements in tardive dyskinesia symptoms 90% of participants who completed 48 weeks of continuous treatment with INGREZZA 40 mg achieved a ≥50% improvement in the Abnormal Involuntary Movement Scale Total Score INGREZZA is the only vesicular monoamine transporter 2 (VMAT2) inhibitor that allows patients to start immediately at a therapeutic dose without required titration SAN DIEGO, Oct. 17, 2025 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced the presentation of a new post-hoc analysis from the Phase 3, open-label KINECT® 4 study, demonstrating that patients treated continuously for 48 weeks with the 40 mg dose of once-daily INGREZZA® (valbenazine) capsules experienced clinically meaningful improvements in tardive dyskinesia symptoms. Findings will be presented at the American Psychiatric Nurses Association 39th Annual Conference, taking place October 15-18 in New Orleans. "The KINECT 4 post-hoc analysis demonstrated the rapid, sustained, long-term clinical benefit of treatment with INGREZZA at the lowest available dose of 40 mg," said Sanjay Keswani, M.D., Chief Medical Officer, Neurocrine Biosciences. "INGREZZA is the only VMAT2 inhibitor that allows patients to start at a therapeutic dose, stay at that dose or adjust to 60 mg or 80 mg, based on individual response and tolerability. These findings add to previously published data supporting 40 mg as an effective, long-term treatment option." The KINECT 4 Phase 3, open-label study evaluated the long-term efficacy, safety and tolerability of INGREZZA in adults with tardive dyskinesia (TD). Participants in the post-hoc analysis received INGREZZA 40 mg once daily for the first four weeks, with the option to escalate to 80 mg daily at Week 4, based on tolerability and clinical response. From Week 4 through Week 48, dose reduction from 80 mg to 40 mg was permitted based on individual tolerability. This analysis included patients in the INGREZZA 40 mg group (n=45), who received 40 mg throughout the entire study, as well as patients in the INGREZZA 80/40 mg group (n=11), who increased to 80 mg at Week 4 and subsequently reduced to 40 mg. Efficacy was evaluated at all post-baseline visits through end of treatment (Week 48) using clinician- and patient-reported changes in TD severity, as measured by the Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression of Change-TD (CGI-TD) and Patient Global Impression of Change (PGIC). Efficacy outcomes demonstrated that clinically meaningful improvements in TD were sustained throughout the 48-week treatment period in both the INGREZZA 40 mg and INGREZZA 80/40 mg groups: At all post-baseline visits (Week 4 to Week 48), the mean change from baseline in AIMS total score exceeded the minimally clinical important difference threshold, demonstrating rapid and continuous improvements with INGREZZA treatment. Among those who received 40 mg throughout the entire study, the percentage of participants meeting the AIMS response threshold (≥50% total score improvement from baseline) generally increased over time, with 90% (18/20) of those completing 48 weeks reaching this threshold. The analysis also showed that patients who reduced their dose from 80 mg to 40 mg for tolerability reasons achieved similar therapeutic benefits. From Week 8 through Week 48, more than half of all participants across both treatment groups met the response threshold for CGI-TD and PGIC, with 90% (18/20) of participants on continuous INGREZZA 40 mg treatment being "much improved" or "very much improved" at Week 48 per clinician assessment (CGI-TD) and patient self-report (PGIC). Efficacy outcomes with INGREZZA 40 mg were comparable to those achieved with 80 mg in the original KINECT 4 study. In the study, safety and tolerability of treatment was consistent with the known profile of INGREZZA with no new concerns identified, and most treatment-emergent adverse events were mild or moderate in intensity. The most common side effects of INGREZZA in people with TD are sleepiness and tiredness. Additional presentations at the American Psychiatric Nurses Association 39th Annual Conference: Physical, Mental, and Socioemotional Functional Improvement Following Valbenazine Treatment for TD: A Case Series Estimation of the Minimal Clinically Important Difference and Longitudinal Change in the Tardive Dyskinesia Impact Scale, a Validated, Tardive Dyskinesia-Specific, Patient-Reported Outcome Measure Once-Daily Valbenazine Improves the Impacts and Symptoms of Tardive Dyskinesia in Patients: Results From the Phase 4 KINECT-PRO Study Valbenazine Improves Physical, Social, and Emotional Impacts on the Tardive Dyskinesia Impact Scale (TDIS): Post Hoc Analyses of KINECT-PRO Data About Tardive Dyskinesia Tardive dyskinesia (TD) is a movement disorder that is characterized by uncontrolled, abnormal and repetitive movements of the face, torso and/or other body parts, which may be disruptive and negatively impact patients. The condition is associated with taking certain kinds of mental health medicines (antipsychotics) that help control dopamine receptors in the brain. Taking antipsychotics commonly prescribed to treat mental illnesses such as major depressive disorder, bipolar disorder, schizophrenia and schizoaffective disorder and other prescription medicines (metoclopramide and prochlorperazine) used to treat gastrointestinal disorders are associated with TD. In patients with TD, these treatments are thought to result in irregular dopamine signaling in a region of the brain that controls movement. The symptoms of TD can be mild to severe and are often persistent and irreversible. TD is estimated to affect at least 800,000 adults in the U.S. About the KINECT 4 Phase 3 Study KINECT 4 is a Phase 3, open-label study in which 163 participants with moderate to severe TD and underlying schizophrenia, schizoaffective disorder or mood disorder (including bipolar disorder or major depressive disorder) received 48 weeks of open-label treatment with once-daily INGREZZA (40 mg or 80 mg capsules) followed by a four-week washout. Dosing was initiated at 40 mg/day in all participants, with escalation to 80 mg/day at Week 4 based on effectiveness and tolerability. Dose reduction to 40 mg was allowed in participants who could not tolerate the 80 mg dose. Patients were discontinued if the new dose was not tolerated. Participants experienced TD improvements during long-term treatment as demonstrated by mean change from baseline to Week 48 in AIMS total score (sum of items 1-7, evaluated by site raters) with INGREZZA 40 mg/day (-10.2) or 80 mg/day (-11.0). Consistent with previous studies, INGREZZA was generally well tolerated. After Week 4, treatment-emergent adverse events that occurred in ≥5% of all participants (combined dose groups) were urinary tract infection (8.5%) and headache (5.2%). Changes from baseline in psychiatric stability, vital signs, electrocardiogram parameters and laboratory test values were generally small and not clinically significant. About INGREZZA ® (valbenazine) Capsules and INGREZZA® SPRINKLE (valbenazine) Capsules INGREZZA is a selective vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of adults with tardive dyskinesia and the treatment of chorea associated with Huntington's disease (HD). Only INGREZZA offers a therapeutic dose from day one with no required titration. INGREZZA, developed by Neurocrine Biosciences, selectively inhibits VMAT2 with no appreciable binding affinity for VMAT1, dopaminergic (including D2), serotonergic, adrenergic, histaminergic or muscarinic receptors. While the specific way INGREZZA works to treat TD and HD chorea is not fully understood, INGREZZA is unique in that it selectively and specifically targets VMAT2 to inhibit the release of dopamine, a chemical in the brain that helps control movement. INGREZZA is believed to reduce extra dopamine signaling, which may lead to fewer uncontrollable movements. INGREZZA is studied across the widest range of patients. It is always one capsule, once daily and can be taken together with most stable mental health regimens such as antipsychotics or antidepressants. Only INGREZZA offers the benefit of a sprinkle formulation, INGREZZA SPRINKLE, for those who experience dysphagia, have difficulty swallowing or prefer not to swallow a pill. INGREZZA and INGREZZA SPRINKLE dosages approved for use are 40 mg, 60 mg and 80 mg capsules. Important Information Approved Uses INGREZZA® (valbenazine) capsules or INGREZZA® SPRINKLE (valbenazine) capsules are prescription medicines used to treat adults with: movements in the face, tongue, or other body parts that cannot be controlled (tardive dyskinesia). involuntary movements (chorea) of Huntington's disease. INGREZZA or INGREZZA SPRINKLE do not cure the cause of involuntary movements, and do not treat other symptoms of Huntington's disease, such as problems with thinking or emotions. It is not known if INGREZZA or INGREZZA SPRINKLE is safe and effective in children. IMPORTANT SAFETY INFORMATION INGREZZA or INGREZZA SPRINKLE can cause serious side effects in people with Huntington's disease, including: depression, suicidal thoughts, or suicidal actions. Tell your healthcare provider before you start taking INGREZZA or INGREZZA SPRINKLE if you have Huntington's disease and are depressed (have untreated depression or depression that is not well controlled by medicine) or have suicidal thoughts. Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings. This is especially important when INGREZZA or INGREZZA SPRINKLE is started and when the dose is changed. Call your healthcare provider right away if you become depressed, have unusual changes in mood or behavior, or have thoughts of hurting yourself. Do not take INGREZZA or INGREZZA SPRINKLE if you: are allergic to valbenazine, or any of the ingredients in INGREZZA or INGREZZA SPRINKLE. INGREZZA or INGREZZA SPRINKLE can cause serious side effects, including: Allergic reactions. Allergic reactions, including an allergic reaction that causes sudden swelling called angioedema, can happen after taking the first dose or after many doses of INGREZZA or INGREZZA SPRINKLE. Signs and symptoms of allergic reactions and angioedema include: trouble breathing or shortness of breath, swelling of your face, lips, eyelids, tongue, or throat, or other areas of your skin, trouble with swallowing, or rash, including raised, itchy red areas on your skin (hives). Swelling in the throat can be life-threatening and can lead to death. Stop taking INGREZZA or INGREZZA SPRINKLE and go to the nearest emergency room right away if you develop these signs and symptoms of allergic reactions and angioedema. Sleepiness and tiredness that could cause slow reaction times (somnolence and sedation). Do not drive a car or operate dangerous machinery until you know how INGREZZA or INGREZZA SPRINKLE affects you. Drinking alcohol and taking other medicines may also cause sleepiness during treatment with INGREZZA or INGREZZA SPRINKLE. Heart rhythm problems (QT prolongation). INGREZZA or INGREZZA SPRINKLE may cause a heart rhythm problem known as QT prolongation. You have a higher chance of getting QT prolongation if you also take certain other medicines during treatment with INGREZZA or INGREZZA SPRINKLE. Tell your healthcare provider right away if you develop any signs or symptoms of QT prolongation, including: fast, slow, or irregular heartbeat (heart palpitations), shortness of breath, dizziness or lightheadedness, or fainting or feeling like you are going to faint. Neuroleptic Malignant Syndrome (NMS). NMS is a serious condition that can lead to death. Call a healthcare provider right away or go to the nearest emergency room if you develop these symptoms and they do not have another obvious cause: high fever, stiff muscles, problems thinking, irregular pulse or blood pressure, increased sweating, or very fast or uneven heartbeat. Parkinson-like symptoms. Symptoms include: body stiffness, drooling, trouble moving or walking, trouble keeping your balance, shaking (tremors), or falls. Before taking INGREZZA or INGREZZA SPRINKLE, tell your healthcare provider about all of your medical conditions including if you: have liver or heart problems, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Make sure you tell all of your healthcare providers that you are taking INGREZZA or INGREZZA SPRINKLE. Taking INGREZZA or INGREZZA SPRINKLE with certain other medicines may cause serious side effects. Especially tell your healthcare provider if you: take digoxin or take or have taken a monoamine oxidase inhibitor (MAOI) medicine. You should not take INGREZZA or INGREZZA SPRINKLE if you are taking, or have stopped taking, a MAOI within the last 14 days. The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with tardive dyskinesia are sleepiness and tiredness. The most common side effects of INGREZZA or INGREZZA SPRINKLE in people with chorea associated with Huntington's disease include sleepiness and tiredness, raised itchy red areas on your skin (hives), rash, and trouble getting to sleep or staying asleep. These are not all of the possible side effects of INGREZZA or INGREZZA SPRINKLE. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit MedWatch at or call 1-800-FDA-1088. Dosage Forms and Strengths: INGREZZA and INGREZZA SPRINKLE are available in 40 mg, 60 mg, and 80 mg capsules. Please see full Prescribing Information, including Boxed Warning, and Medication Guide. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, classic congenital adrenal hyperplasia, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X and Facebook. (*in collaboration with AbbVie) The NEUROCRINE BIOSCIENCES Logo, NEUROCRINE, YOU DESERVE BRAVE SCIENCE, INGREZZA and KINECT are registered trademarks of Neurocrine Biosciences, Inc. KINECT-PRO and TDIS are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statements In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from INGREZZA and the value INGREZZA may bring to patients. Factors that could cause actual results to differ materially from those stated or implied in the forward-looking statements include, but are not limited to, the following: risks and uncertainties associated with Neurocrine Biosciences' business and finances in general, as well as risks and uncertainties associated with the commercialization of INGREZZA; whether INGREZZA receives adequate reimbursement from third-party payors; risks and uncertainties relating to competitive products and technological changes that may limit demand for INGREZZA; risks associated with the Company's dependence on third parties for development and manufacturing activities related to INGREZZA, and the ability of the Company to manage these third parties; risks that additional regulatory submissions for INGREZZA or other product candidates may not occur or be submitted in a timely manner; risks that the FDA or other regulatory authorities may make adverse decisions regarding INGREZZA; risks that post-approval INGREZZA commitments or requirements may be delayed; risks that INGREZZA may be precluded from commercialization by the proprietary or regulatory rights of third parties, or have unintended side effects, adverse reactions or incidents of misuse; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended June 30, 2025. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof other than required by law. © 2025 Neurocrine Biosciences, Inc. All Rights Reserved. CAP-VBZ-US-0084 10/2025 SOURCE Neurocrine Biosciences, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED