Nortriptyline Hydrochloride

点击上方“蓝字”关注我们吧！ 帕金森病情绪障碍       帕金森病是一种复杂的神经退行性疾病，同时伴有运动和非运动症状，越来越多的研究证实非运动症状通常发生在运动症状之前，如情绪低落、疼痛、疲劳和睡眠障碍等。在非运动症状中，情绪障碍发生在多达35%的帕金森病患者中，这对患者及其护理人员的生活质量产生了实质性的负面影响。情绪障碍给经济、社会和个人带来了严重的负担。因此，为了优化患者治疗效果，需要对情绪障碍进行积极管理。1        2024年《Lancet》上发表的《Medical, surgical, and physical treatments for Parkinson's disease》，对情绪障碍的治疗选择进行了归纳总结。 常见的情绪障碍 焦虑和抑郁 抑郁是帕金森病常见的非运动症状，发生率为2.7%～90.0%，可贯穿帕金森病全病程，有时可在运动症状出现之前发生，是帕金森病的前驱症状之一。抑郁症既可随运动波动而变化，表现为“关”期抑郁，也可与运动症状无明确相关。帕金森病焦虑主要表现为广泛性焦虑、惊恐障碍和社交障碍，并以两者居多，常与抑郁症状相伴。2     淡漠     淡漠是指缺乏动力和进取心，对外界事物漠不关心的状态。帕金森病患者中淡漠发生率约39.8%，可与抑郁、疲劳和认知功能障碍等症状伴发，也可单独出现。2 治疗选择 焦虑和抑郁 对于有焦虑、抑郁的患者，在出现运动症状时开始使用多巴胺能治疗，也能减轻其抑郁和焦虑。单胺氧化酶B（MAO-BIs）可能缓解早期帕金森病的抑郁，但似乎晚期作用较弱。多巴胺受体激动剂（DAs）作为抗抑郁药时，对抑郁症的益处大于对改善运动症状的作用，而多巴胺受体激动剂的副作用会限制其临床应用，包括冲动控制障碍、睡眠功能障碍等。 三环类抗抑郁药、5-羟色胺选择性再摄取抑制剂（SSRIs）和5-羟色胺-去甲肾上腺素再摄取抑制剂（SNRIs）在治疗帕金森病患者抑郁症方面的疗效，虽在少数几个试验中评估的结果不相同，但总体上是积极的，不过迄今为止，在帕金森病患者中尚无这几类抗抑郁药的大型比较试验。一项纳入408名帕金森病患者的随机对照试验目前正在进行中，比较了艾司西酞普兰、去甲替林和安慰剂治疗8周，随访12个月对于帕金森病患者抑郁的效果，这项试验可能为帕金森病抑郁症状的治疗选择提供新的证据。 帕金森病焦虑治疗的循证医学证据不足，同时意味着目前药物治疗依赖于广泛使用的抗焦虑药，包括苯二氮䓬类药物和抗抑郁药。 （图表源自参考资料3） 近年来，情绪的非药物治疗选择有所增加。在抑郁方面，重复经颅磁刺激对非帕金森病抑郁症的老年患者有效，但帕金森病相关抑郁症的患者使用较少；认知行为疗法，包括使用线上的方式，已经显示出对抑郁和焦虑的益处；光照疗法可能对抑郁症有好处，并可能对睡眠有额外作用。在焦虑方面，最近有报道称，经过8周的针灸后可以改善焦虑；由于外部压力因素（如离开熟悉的环境）而加剧的焦虑也需要加以管理；此外，由于帕金森病患者容易产生社会孤立感，社会处方（例如参与社会活动等）也被认为是一种有效的非药物治疗方式，能够显著改善患者的焦虑症状。3     淡漠     淡漠在帕金森病患者中可能很普遍，但治疗起来非常困难，尚缺乏足够的循证医学证据。多巴胺受体激动剂中，吡贝地尔可能有效，罗替高汀需要进一步研究。胆碱酯酶抑制剂中，卡巴拉汀在临床上是有效的。 同时职业疗法对个体的益处也很重要，除能改善身体活动、书写、日常生活活动和生活质量以外。职业疗法对于解决非运动症状也很重要，包括认知障碍、焦虑、疲劳、睡眠障碍和淡漠。3 新药获批 2024年12月1日，甲磺酸沙非胺片获国家药品监督管理局（NMPA）批准用于治疗原发性帕金森病伴症状波动（包括剂末恶化和开-关现象）成人患者的联合治疗！甲磺酸沙非胺片具有多巴胺能和非多巴胺能双重机制，可显著改善帕金森病患者症状波动、运动症状、非运动症状，并且能长期有效提高生活质量。 诸多文献提示伴随情绪障碍的帕金森病患者的有效治疗仍然是一个亟待解决的问题，而越来越多的证据表明谷氨酸系统功能障碍直接参与其中。沙非胺正是一种兼具单胺氧化酶B可逆抑制和通过状态依赖性钠通道阻断过度谷氨酸释放作用的帕金森病治疗药物。 一项016研究和018研究数据的事后分析，评估了100mg沙非胺与安慰剂相比，对PDQ-39“情绪健康”域得分、GRID-HAMD量表得分和报告抑郁不良事件的患者比例的影响，证实了沙非胺对帕金森病患者的情绪健康有显著的临床获益。 该分析显示，与安慰剂相比，在治疗6个月时，沙非胺100mg明显改善PDQ-39“情绪健康”域评分3.77分(95% CI: -6.49，-1.05; p = 0.0067)，并可长期维持疗效（2年），在治疗24个月时，改善PDQ-39“情绪健康”域评分4.66分(95% CI: -7.30，-2.02; p = 0.0006)。 （图表源自参考资料1） 在抑郁方面，与安慰剂组相比，在治疗6个月时，沙芬胺100mg能改善GRID-HAMD评分0.57分（95% CI: -1.13，-0.02; p = 0.0408)，同样该疗效可长期维持（2年），在治疗24个月时，改善GRID-HAMD评分0.87分（95% CI: -1.44， -0.30; p = 0.0027)。 （图表源自参考资料1） 在报告抑郁不良事件的患者比例方面，与安慰剂相比，在治疗6个月时，服用沙非胺100mg患者报告的抑郁不良事件显著减少(分别为1.8% vs 5.4%，p = 0.0444)，并且服用沙非胺的患者报告抑郁不良事件的比例在长期内保持稳定，而安慰剂组则有所增加(在24个月时，分别为1.7% vs 8.0%，p = 0.0057)。1 （图表源自参考资料1） 值得关注的是沙非胺还在非运动症状综合管理方面表现出多维度的治疗获益，包括但不限于情绪、疼痛、睡眠障碍、自主神经功能调节改善等，有望能为帕金森病全程管理提供新的治疗范式，为改善帕金森病患者的生活质量带来显显改善。4 参考文献 1.Cattaneo C, Müller T, Bonizzoni E, Lazzeri G, Kottakis I, Keywood C. Long-Term Effects of Safinamide on Mood Fluctuations in Parkinson's Disease. J Parkinsons Dis. 2017;7(4):629-634. 2.中华医学会神经病学分会帕金森病及运动障碍学组,中国医师协会神经内科分会帕金森病及运动障碍学组. 帕金森病非运动症状管理专家共识（2020）[J]. 中华医学杂志,2020,100(27)：2084-2091. 3.Foltynie T, Bruno V, Fox S, Kühn AA, Lindop F, Lees AJ. Medical, surgical, and physical treatments for Parkinson's disease. Lancet. 2024 Jan 20;403(10423):305-324.  4.Santos García D, Labandeira Guerra C, Yáñez Baña R, Cimas Hernando MI, Cabo López I, Paz Gonález JM, Alonso Losada MG, González Palmás MJ, Martínez Miró C. Safinamide Improves Non-Motor Symptoms Burden in Parkinson's Disease: An Open-Label Prospective Study. Brain Sci. 2021 Mar 2;11(3):316. 提示：本材料仅供医疗卫生专业人士进行医学科学交流，不用于推广目的。

FRIDAY, March 24, 2023 -- Endless worry, irritability and insomnia are all symptoms of a possible anxiety disorder . Luckily, there are numerous anxiety medications that can help ease the condition. Joy Alonzo , a specialist in the pharmacotherapy of mental disorders at Texas A&M's College of Pharmacy, said recently, “If you understand the different types of medication, then you can become a better advocate for your anxiety treatment. Anxiety is one of the most under-treated mental illnesses, and we need to talk more about it.” So, what medications can bring relief from crippling anxiety? According to the Anxiety & Depression Association of America (ADAA), the most common classes of drugs for the treatment of anxiety include: Selective serotonin reuptake inhibitors (SSRIs) Serotonin-norepinephrine reuptake inhibitors (SNRIs) Benzodiazepines Tricyclic antidepressants Here is a rundown on medications for anxiety. Selective serotonin reuptake i nhibitors (SSRIs) SSRIs work by preventing the body from reabsorbing serotonin, which leaves more available for use. The ADAA describes serotonin as a neurotransmitter that plays a role in feelings of well-being and happiness. SSRIs are considered the first-line treatment for all types of anxiety disorders. A higher dose may be required when treating obsessive-compulsive disorder (OCD). Common side effects : Insomnia Sleepiness Sexual dysfunction Weight gain Dry mouth Common SSRIs: Citalopram ( Celexa ) Escitalopram ( Lexapro ) Fluoxetine ( Prozac , Sarafem ) Paroxetine ( Paxil , Paxil CR , Pexeva , Brisdelle ) Sertraline ( Zoloft ) What else you should know about SSRIs: SSRIs may make it easier to engage in psychotherapy and other wellness activities They may help improve other symptoms of anxiety, including headaches and sleep disturbances Initial side effects typically disappear after four to eight weeks SSRIs are safe for long-term use Check with your provider before stopping their use or changing your dose Serotonin-norepinephrine reuptake inhibitors (SNRIs) This class of medication is also a first-line treatment for anxiety disorders, except for OCD. It works by inhibiting the brain cells' reabsorption of both serotonin and norepinephrine. Serotonin is the neurotransmitter that helps with a sense of well-being. According to Anxiety.org , norepinephrine is considered important for its role in the body’s stress response. Common side effects: Anxiety.org states that SNRIs may have more side effects because they affect serotonin and norepinephrine. These side effects may include: Dry mouth Nausea Nervousness Insomnia Drowsiness Dizziness Headache Sexual dysfunction Loss of appetite Agitation Common SNRIs: Venlafaxine (Effexor) Desvenlafaxine ( Pristiq ) Duloxetine ( Cymbalta ) What else you should know about SNRIs Anxiety.org reports that these medications promote neuroplasticity in the brain. This may make your brain more flexible. There is evidence that these medications work best in combination with psychotherapy. But there is one important caveat. “SSRIs and SNRIs are not an instant fix for symptoms associated with an anxiety disorder, nor do they even provide immediate relief,” Alonzo said. “They work by interacting with the neurotransmitters and receptors in your brain, which can help regulate mood, sleep and energy levels. It is important for patients to understand that these medications may take four to six weeks for full effect.” Benzodiazepines Benzodiazepines are considered a second-line therapy for the treatment of generalized anxiety disorder. According to the ADAA, they work by strengthening the GABA neurotransmitter. This neurotransmitter plays a primary role in feeling calm, muscle relaxation, reduction in brain activity and sleep. Most common side effects: Drowsiness Confusion Dizziness Depression Impaired coordination Vision problems Common benzodiazepines: Alprazolam ( Xanax ) Lorazepam ( Ativan ) Diazepam ( Valium ) What else you should know about benzodiazepines for the treatment of anxiety: They act quickly, but do not stay in the system for long They are not safe for continuous use, and can be addictive May be initiated with a first-line treatment, and then tapered off Do not operate heavy equipment while taking Do not mix with alcohol Not recommended for people with suicidal or addictive tendencies Tricyclic antidepressants According to the Mayo Clinic , tricyclic antidepressants are among the earliest antidepressants. They are often recommended when newer drugs have not been effective. They are not typically used for social anxiety disorder or OCD. They also work by blocking the reabsorption of serotonin and norepinephrine, but their mechanism of action is different and they typically cause more side effects than newer treatments. Common tricyclic antidepressants: Imipramine (Tofranil) Nortriptyline (Pamelor) Desipramine (Norpramin) Clomipramine (Anafranil) Common side effects: Drowsiness Blurred vision Constipation Dry mouth Drop in blood pressure when going from sitting to standing Urine retention Weight loss/weight gain Excessive sweating Tremor Sexual dysfunction What else you should know about tricyclic antidepressants: You should not stop taking these medications abruptly You may need to have blood work done to determine the correct dose Disorientation can occur in older people at higher doses May cause a rapid or irregular heart rate Can increase seizure activity if prone to seizures When to seek treatment for anxiety The National Institute of Mental Health lists these as common symptoms of anxiety: Feeling restless, wound up or on edge Being easily fatigued Having difficulty concentrating Being irritable Having headaches, muscle aches, stomach aches or unexplained pains Difficulty controlling feelings of worry Having sleep problems, such as difficulty falling or staying asleep The ADAA recommends seeking medication for anxiety when you are having physical symptoms, are unable to do what you want because of how you feel or are unable to make life choices because of fear. It is never too early to start treatment. Anxiety treatment can be more effective when used with therapy. It is essential to keep all your appointments with your provider. Do not stop your medication or change the dose without discussing it with your provider. If the side effects affect your daily activities, inform your provider immediately. If, at any time, you feel as though you may be suicidal, reach out to your provider or go to the nearest emergency room. You can also call or text the national suicide prevention hotline at 988. Posted March 2023