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Study of 2,197 patients with resistant depression finds 95 percent improved once parasympathetic and sympathetic imbalances were identified and corrected What we found, again and again, was that these patients were not treatment resistant in any meaningful psychiatric sense. Their brains were being starved of blood.” — Dr. Joe Colombo, Franklin Cardiovascular, Sicklerville, New Jersey, USA SICKLERVILLE, NJ, UNITED STATES, March 31, 2026 / EINPresswire.com / -- Consider a house with the water main half shut. The faucets sputter. The toilet runs all night. The garden wilts. You could call a plumber for the faucet, a landscaper for the garden, a different plumber for the toilet, and every one of them would fix something while fixing nothing. The water main stays half shut. The house stays thirsty. Something analogous, and far more consequential, has been happening inside the bodies of millions of people diagnosed with depression. They arrive at psychiatry offices carrying years of pharmaceutical sediment: SSRIs layered over SNRIs layered over atypical antipsychotics, dosages revised and stacked and titrated upward until the side effects rival the illness itself. Eventually somebody writes the words "treatment resistant" in a chart, and the search, for too many, ends there. A new peer-reviewed study published in Brain Medicine suggests the search has been ending in the wrong place. Blood, gravity, and the brain that cannot wait form the central narrative of the research. The study, conducted across three clinical practices in the Philadelphia, Memphis, and New York City areas over six years, followed 8,128 consecutive patients with documented autonomic dysfunction, a condition in which the involuntary nervous system fails to properly regulate basic bodily functions. Of those, 2,197 carried prior diagnoses of depression or depression-like symptoms. They were, on average, 49.5 years old. Just under 58 percent were female. They arrived burdened not with one or two complaints but with an average of 23.2 out of 28 possible autonomic symptoms: fatigue so dense it felt architectural, brain fog that swallowed nouns mid-sentence, lightheadedness upon standing, sleep that never restored, memory lapses, gastrointestinal chaos, hormone dysregulation (especially in women's health), chronic pain, chronic headache or migraines, rashes, and sensory disturbances that made light too bright and sound too loud. Every single one of them, at baseline, demonstrated measurable dysfunction of the parasympathetic and sympathetic nervous systems, the two branches of the autonomic system that together orchestrate every involuntary function the body performs. Two specific derangements emerged as the primary villains. Alpha-sympathetic withdrawal, present in 79.5 percent of the depression subpopulation, causes blood to pool in the lower extremities when a patient stands or sits up. The brain, perched at the top of the body like a penthouse apartment at the end of a failing water main, gets shorted. Parasympathetic excess, found in 54.6 percent, triggers inappropriate vasodilation (the vessels relaxing when they should be holding firm), forcing the heart to labor harder merely to keep the brain adequately supplied. Note that this can worsen in susceptible women during the menstrual cycle because fluctuations in estrogen and progesterone alter vascular tone and autonomic regulation, sometimes making it harder for the cardiovascular system to maintain adequate blood flow to the brain in the upright position. A third dysfunction, beta-sympathetic excess (27.8 percent), appeared largely as a compensatory response: the cardiac engine revving to fight gravity. All three conspire toward the same destination. Poor cerebral perfusion. A brain running on less oxygen and glucose than it requires to think, to feel, to distinguish Wednesday from the end of the world. Understanding why the old instruments heard the wrong song requires a critical methodological distinction. Standard autonomic monitoring techniques, the kind used in most cardiology and neurology labs, measure total autonomic activity. They take the combined signal from parasympathetic and sympathetic outputs and attempt to infer each branch by approximation. It is, roughly speaking, like trying to hear two musicians in a duet by listening to the recording through a single speaker and guessing which notes belong to the violin and which to the cello. The study team employed a different approach. P&S Monitoring adds an independent measure of respiratory activity to the standard heart rate variability signal, mathematically separating the parasympathetic from the sympathetic contribution without assumptions or approximations. The distinction is not academic. Without it, a clinician cannot determine whether the sympathetic system is genuinely overactive or merely compensating for a parasympathetic problem. Get that wrong, and your treatment does not just fail. It makes things worse. A nervous system cannot be rushed, which is why treatment followed what the authors call a "low-and-slow" philosophy. Higher doses of medication, in this population, do not accelerate recovery. They cause more autonomic dysfunction and thereby more symptoms. The nervous system must be coaxed, not bludgeoned. Prescription options included low-dose Midodrine (2.5 mg three times daily) for sympathetic withdrawal and low-dose Nortriptyline (10 mg, taken twelve hours before waking) for parasympathetic excess, both at homeostatic rather than therapeutic doses. For patients who could not tolerate pharmaceuticals, R-alpha-lipoic acid (600 mg three times daily) addressed sympathetic withdrawal by healing mitochondria and restoring nerve function, while six months of gentle, structured walking, no faster than two miles per hour, targeted parasympathetic excess. That walking protocol was originally developed for astronauts returning from space with deconditioned hearts. The parallel is not poetic license. The autonomic dysfunction in these patients causes the heart to behave as if it were living in zero gravity. Note, this is why many of these patients do not receive the restorative and refreshing sleep they desire. For as soon as they lie down, their brains receive all the blood they want and "wake up and want to play," the patient wants to fall asleep. This merely exacerbates the "wired-tired" feeling most autonomic patients report. Within three months, patients reported improved sleep. That matters enormously in a population running on empty; a single night of restorative rest can shift the entire horizon of what feels possible. Over six to nine months, most physiological symptoms receded. By the end of treatment, averaging 9 to 12 months, the average symptom count had fallen from 23.2 to 5.2 (W = 0.00, p < .001). Fatigue was relieved in 77.4 percent of patients. Sleep difficulties in 77.2 percent. Brain fog in 69.0 percent. And 33 percent of patients finished treatment with three or fewer symptoms remaining. Three. Out of twenty-eight. "We compare the process to breaking a bad habit and establishing a good one. You cannot rush nerve retraining any more than you can rush a fracture. But when patients understand the physiology behind their suffering, when they see that their fatigue and fog have a measurable, mechanical cause, something shifts. They find hope. And hope is what keeps a person in treatment long enough for the nervous system to heal," added Dr. Colombo. Autonomic expert, Adjunct Professor of Internal Medicine, Rowan-Virtua School of Osteopathic Medicine. The long COVID shadow looms large over these findings. Nearly half of the study cohort (48.3 percent) had been diagnosed with long- or post-COVID syndrome, a population now recognized as a vast and troubled reservoir of autonomic dysfunction. Other prominent conditions included orthostatic dysfunction (36.9 percent), hypertension (39.6 percent), and type 2 diabetes (16.9 percent). In many of these patients, the elevated blood pressure that had been medicated as a standalone cardiac problem was, in fact, compensatory, the heart working overtime to push blood past autonomic resistance and up to the brain. Treat the blood pressure without addressing the underlying imbalance, and you lower the number on the cuff while the brain goes hungrier still. Recovery demands a kind of patience that modern medicine rarely rewards. Full rebalancing of the parasympathetic and sympathetic systems requires 15 to 24 months, and the process is fragile, easily set back by stress or illness. Only 9.6 percent of patients abandoned the program, however. The authors attribute this persistence, at least partly, to the early improvement in sleep quality and to the simple, radical act of telling patients that they were believed. What remains uncertain deserves candid acknowledgment. The authors are forthright about the boundaries of what they can claim. This is an observational, single-group design with no explicit control group. Depressive symptoms were assessed not with standardized psychiatric rating scales such as the PHQ-9 or Hamilton but with a 28-item autonomic symptom questionnaire that overlaps with depression. The study carries referral bias, since all patients were seen in specialized autonomic dysfunction practices. It carries survivor and engagement bias, since individuals who remained in treatment for up to two years may differ fundamentally from those who left. The intensive clinician contact and explicit coaching about hope and long timelines may have introduced expectation or placebo effects. The authors themselves recommend what should come next: a blinded, randomized, controlled, crossover study comparing P&S-guided therapy plus usual care versus usual care alone, using standardized depression scales and autonomic endpoints. "For too long, psychiatry has accepted the label of treatment-resistant depression as a verdict rather than a question. This research compels us to ask what we are actually treating. If a significant proportion of patients carrying that diagnosis have measurable autonomic dysfunction fueling their symptoms, then we have a responsibility to screen for it, to measure it, and to address it before concluding that a patient has failed treatment. Perhaps it was not the patient who failed. Perhaps the diagnostic framework failed them," said Dr. Michele T. Pato, first author of the study, from the Department of Psychiatry at Rutgers, The State University of New Jersey. The body must be heard before the mind can be read. What this study describes is not a replacement for psychiatric care. It is something potentially more consequential: a physiological foundation that must be laid before psychiatric care can land where it belongs. Once autonomic function is restored and cerebral perfusion normalized, any symptoms that remain are, by definition, true end-organ psychiatric illness, and they can finally be treated in a focused and individualized manner. The mind, it turns out, cannot be accurately read while the body is still shouting. The work spans cardiology, neurology, and autonomic medicine, and it points toward a future in which the borders between those disciplines and psychiatry grow thinner. For the millions of patients currently warehoused behind the label treatment resistant, that thinning cannot arrive soon enough. The peer-reviewed research article in Brain Medicine titled "Is it really treatment-resistant depression? Parasympathetic and sympathetic dysfunction as a treatable contributor to depressive symptoms," is freely available via Open Access, starting on 31 March 2026 in Brain Medicine at the following hyperlink: https://doi.org/10.61373/bm026r.0024 The full reference for citation purposes is: Pato MT, DePace NL, Weintraub MI, Murray GL, Lill R, Munoz R et al. Is it really treatment-resistant depression? Parasympathetic and sympathetic dysfunction as a treatable contributor to depressive symptoms. Brain Medicine 2026. DOI: https://doi.org/10.61373/bm026r.0024 . Epub 2026 Mar 31. About Brain Medicine: Brain Medicine (ISSN: 2997-2639, online and 2997-2647, print) is a peer-reviewed medical research journal published by Genomic Press , New York. Brain Medicine is a new home for the cross-disciplinary pathway from innovation in fundamental neuroscience to translational initiatives in brain medicine. The journal's scope includes the underlying science, causes, outcomes, treatments, and societal impact of brain disorders, across all clinical disciplines and their interface. Visit the Genomic Press Virtual Library: https://issues.genomicpress.com/bookcase/gtvov/ Our media website is at: https://media.genomicpress.com/ Our full website is at: https://genomicpress.com/ Ma-Li Wong Genomic Press mali.wong@genomicpress.com Visit us on social media: X LinkedIn Bluesky Instagram Facebook Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. 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2025年12月7日，以岭药业的创新中药-芪防鼻通片通过国家医保谈判，首次被纳入《国家医保目录》。该产品是以岭药业自主研发的Ⅰ类中药创新药，用于治疗持续性变应性鼻炎，公司拥有独立完整的知识产品。据公司发布的公告披露，芪防鼻通片于2025年1月获得中国国家药品监督管理局批准上市，2025年7月通过澳门药物监督管理局注册审批，成为首个在澳门获批注册的创新中药。 作为主营专利创新中药的医药企业，以岭药业在专注创新中药的同时，积极布局化生药和健康产业，打造独具特色的中药研发体系。在持续对药品研发高投入的基础上，公司在专利创新中药和化学生物药领域取得丰硕的成果。 一、专利创新中药 以岭药业以络病理论指导临床重大疾病治疗研究，带动专利新药研发，形成了“理论-临床-新药-实验-循证”的产学研一体化新模式。公司围绕重大难治性疾病、中医特色优势、市场需求广泛的产品布局，开发系列拥有自主知识产权的专利中药，在医药行业形成了独具特色的产品阵列优势。 公司目前拥有专利中药17个，覆盖8大临床疾病系统，其中心脑血管系统和感冒呼吸系统疾病用药领域已处于行业领先地位，有11个产品列入国家医保目录，5个产品列入国家基本药物目录。凭借强大的科研实力，公司先后多次承担国家及省部级科研计划项目，荣获国家科技进步一等奖1项、国家科技进步二等奖4项、国家技术发明二等奖1项和省部级科技奖励20余项。 公司与河北以岭医院（三级甲等中医院）开展新药临床合作，以岭医院拥有一百多种院内制剂，是公司开发创新中药的主要产品储备来源。 创新中药研发成果 产品名称 注册分类 适应症或功能主治 注册进展 芪防鼻通片 中药创新药1.1类 过敏性鼻炎 新药批准上市 柴黄利胆胶囊 中药创新药1.1类 慢性胆囊炎 申报新药（撤回申请） 芪桂络痹通片 中药创新药1.1类 类风湿性关节炎 申报新药 半夏白术天麻颗粒 中药新药3.1类 风痰上扰证 申报新药 小儿连花清感颗粒 中药创新药1.1类 儿童感冒 申报新药 柴芩通淋片 中药创新药1.1类 反复发作尿路感染 Ⅱ期临床研究 参蓉颗粒 中药创新药1.1类 肌萎缩侧索硬化症 Ⅱ期临床研究 藿夏感冒颗粒 中药创新药1.1类 感冒风邪夹湿证 Ⅱ期临床研究 连花清咳颗粒 中药改良型新药2.2类 儿童气管-支气管炎 Ⅱ期临床研究 连花御屏颗粒 中药创新药1.1类 感冒气虚证 Ⅱ期临床研究 芪龙定喘片 中药创新药1.1类 慢性阻塞性肺疾病 临床试验申请获批 二、化学生物药 在化学生物药板块，以岭药业制定了“转移加工-仿制药国际国内双注册-专利新药研发国际注册全球销售”齐步走的发展战略。 1.转移加工 在化学生物药业务方面，公司在石家庄、北京建立了普通口服固体制剂、非细胞毒性口服抗肿瘤固体制剂研发生产基地，以及抗肿瘤药物、控缓释剂研发平台，生产车间已通过中国、美国、英国、加拿大、澳大利亚、新西兰等国家的GMP认证。 在合同转移加工业务方面，公司已经成为国内制剂出口欧美等规范市场规模较大的企业之一，产品出口至英国、加拿大、新西兰、澳大利亚等多个国家和地区。 2.仿制药注册 在仿制药业务方面，公司已持有15个美国ANDA产品的批文，并全部在美国上市，1个FDA审评的产品。在中国市场，有13个产品通过一致性评价，有3个美国ANDA产品根据共线生产途径取得国内批文。 在产业链方面，公司在衡水建立了以岭万洋中间体及原料药生产基地，打造了原料及制剂一体化的生产平台，可提供原料药及制剂CDMO服务，还可利用国际注册团队，协助客户完成国际市场的注册及认证工作。 美国ANDA产品获批情况 序号 产品名称 治疗领域 状态 备注 1 阿昔洛韦片 抗病毒 已批准 自研 2 阿昔洛韦胶囊 抗病毒 已批准 自研 3 环丙沙星片 抗生素 已批准 自研 4 非洛地平缓释片 高血压 已批准 自研 5 阿那曲唑片 抗肿瘤 已批准 自研 6 来曲唑片 抗肿瘤 已批准 自研 7 拉莫三嗪缓释片 抗癫痫 已批准 自研 8 伐昔洛韦片 抗病毒 已批准 自研 9 塞来昔布胶囊 抗炎镇痛 已批准 自研 10 帕罗西汀片 抗抑郁 已批准 自研 11 盐酸美金刚片 阿尔兹海默型痴呆 已批准 外购 12 普瑞巴林胶囊 带状疱疹后神经痛 已批准 外购 13 辛伐他汀片 降血脂 已批准 自研 14 喹硫平缓释片 抗精神病 评审中 自研 15 巴氯芬片 肌肉痉挛 已批准 外购 16 米多君片 体位性低血压 已批准 外购 国内通过一致性评价的产品情况 序号 产品名称 治疗领域 状态 备注 1 酒石酸美托洛尔片 高血压 已批准 一致性评价 2 单硝酸异山梨酯片 冠心病 已批准 一致性评价 3 盐酸二甲双胍片 糖尿病 已批准 一致性评价 4 盐酸环丙沙星片 抗生素 已批准 一致性评价 5 卡托普利片 高血压 已批准 一致性评价 6 氢溴酸右美沙芬片 镇咳 已批准 一致性评价 7 格列喹酮片 糖尿病 已批准 一致性评价 8 阿奇霉素片 抗生素 已批准 一致性评价 9 克拉霉素片 抗生素 已批准 一致性评价 10 格列吡嗪片 糖尿病 已批准 一致性评价 11 替硝唑片 抗生素 已批准 一致性评价 12 罗红霉素片 抗生素 已批准 一致性评价 13 厄贝沙坦分散片 高血压 已批准 一致性评价 14 来曲唑片 抗肿瘤 已批准 中美共线生产 15 阿那曲唑片 抗肿瘤 已批准 中美共线生产 16 塞来昔布胶囊 抗炎镇痛 已批准 中美共线生产 国内ANDA产品获批情况 序号 产品名称 治疗领域 状态 备注 1 盐酸伐昔洛韦片 带状疱疹 已批准 自研 3.化学专利新药研发 公司继续加大一类化学创新药研发力度，寻找成熟的和早起介入的青苗类合作项目，构建核心竞争优势，形成一类化学创新药、505B（2）、高端仿制药的优势产品群，以原料药基地做保障，奠定化药核心竞争优势地位。 化药临床新药研发情况 序号 产品名称 适应症或功能主治 注册进展 1 苯胺洛芬注射液 术后疼痛（化药2.1类、2.2类） 批准上市 2 XY0206片 实体瘤、急性髓性白血病 三期临床 3 XY03-EA片 缺血性脑卒中 临床2b阶段 4 G201胶囊 辅助生殖 临床2期阶段 4.化学原料药 公司在河北省衡水县投入建设原料药生产基地，目前已经完成一期建设，主要生产医药中间体、大宗原料药、特色原料药等产品。 原料注册批件 序号 产品名称 适应症或功能主治 注册进展 1 来曲唑片 乳腺癌 原料药批准上市 2 达格列净 糖尿病 原料药批准上市 3 盐酸美金刚 阿尔兹海默型痴呆 原料药批准上市 4 阿那曲唑 雌激素相关肿瘤 原料药批准上市 三、研发投入情况 公司每年投入大量资金用于科研创新，研发投入占比较高，处于同行业领先水平。 2025年上半年 2024年 2023年 2022年 研发投入金额（亿元） 3.99 9.08 9.35 8.95 研发投入占营业收入比例 9.87% 13.94% 9.06% 7.15% 研发投入占净资产比例 3.67% 8.90% 8.17% 8.20% 四、研发人员情况 2024年 2023年 2022年 研发人员数量（人） 1516 1807 1908 研发人员数量占比 12.94% 12.95% 12.66% 研发人员学历结构 本科 1156 1417 1496 硕士 335 363 383 博士 25 27 29 研发人员年龄构成 30岁以下 735 836 883 30-40岁 650 741 782 40-50岁 118 205 216 50-60岁 13 25 27 五、总结 研发创新是医药企业发展和持续增长的核心驱动力，以岭药业通过“高投入+强转化”的模式，在创新中药、仿制药、化学专利新药研发和原料药等领域同时布局，构建了“上市一批、申报一批、研发一批”的研发管线梯队，产品结构丰富，兼顾中长期布局，确保未来多年增长动力不断。 短期来看，自主研发的Ⅰ类中药创新药芪防鼻通片，2025年1月获得中国国家药品监督管理局批准上市，2025年7月通过澳门药物监督管理局注册审批，成为首个在澳门获批注册的创新中药。芪桂络痹通片（类风湿关节炎）、小儿连花清感颗粒（⼉童感冒）、半夏白术天麻颗粒（经典名方）等4款中药新药已提交上市申请，即将进⼊商业化阶段，其中小儿连花清感颗粒将填补⼉童呼吸领域空白，进⼀步完善”大呼吸“矩阵。 中期来看，有5款中药、3款化药处于临床阶段，覆盖尿路感染、胃肠型感冒等多个适应症；长期来看，上百个院内制剂构成新药研发的”储备军“，形成可持续的创新梯队。 对于化学药及原料药，公司已有1个创新药品种获得批准上市，3个创新药品种进入临床阶段，多个创新药处于临床前研究阶段，4个化学原料药获得批准上市。 在国际化布局方面，通心络胶囊、参松养心胶囊、连花清瘟、八子补肾等产品进入50多个国家和地区，芪防鼻通片的澳门获批为中药创新出海提供范本。百余个海内外络病专业委员会的建立，构建了全球学术交流与成果转化的平台。