埃里克·梅萨莫尔 是东北俄亥俄医科大学的精神病学家和精神病学副教授。他担任大学精神分裂症治疗最佳实践 (BeST) 中心的医学主任。他拥有药理学医学博士和博士学位。 Messamore 博士还曾在 CURESZ 基金会董事会任职。

氯氮平以其他药物无法做到的方式挽救生命并改善生活质量。氯氮平是治疗约 20% 精神分裂症患者的最佳药物，但在美国仅用于 4%。这意味着大约 16% 的精神分裂症患者（将近 50 万人）无法享受这种无与伦比的药物所能实现的生活质量。我曾经在一家州立医院工作，成为一位患有精神分裂症的女士的医生。让我们称她为“安娜”。大约 20 年来，她一直生病，辗转于医院、街头，有时甚至是监狱。作为一个患有严重精神疾病的无家可归者，她经历了许多非常可怕的创伤。安娜从未尝试过氯氮平，因为：1) 医生认为她不会定期服药，或者她的“生活方式”太混乱以至于无法参加每周的血液检查； 2) 她非常害怕打针，所以无论如何都会拒绝氯氮平。

To address her fear of needles, I prescribed an anesthetic cream that we would rub into the spot where we were would draw blood. The anesthetic cream numbed the skin and helped Anna feel comfortable with blood testing so she agreed to try clozapine.

不到两个月，我们就见到了真正的安娜。她是一位令人愉快的女士，有幽默感。自生病以来，她第一次能够积极参与她的出院计划。

她定期服药，因为她觉得这真的对她有帮助。 （她之所以停止服用之前的药物，是因为它们并没有真正以对她重要的方式提供帮助。）她继续拥有自己的公寓，并开始过上自己想要的生活。氯氮平帮助她打破了疾病和无家可归的恶性循环，让安娜重新过上了她能掌控的生活。

出于各种原因，美国的许多医生不向他们的精神分裂症患者提供氯氮平。这些天我的部分工作是协助医生或精神科执业护士使用氯氮平，让他们亲眼看到像安娜这样的成功案例实际上很常见这种独特有效的药物。

I’m not a fan of labels like “wonder drug” for medications. The most successful outcomes are usually the result of treatment that combines multiple approaches like psychotherapy, environmental modification, bolstering social support, and helping people to reconnect to the things in life that give them meaning, purpose, and joy. Labeling a particular medication “miraculous” creates a risk of over-focusing on one approach even when others are also valuable. On the other hand, clozapine does appear to have a higher level of treatment effectiveness than any other medication for schizophrenia and can be uniquely effective in cases where other medications have failed. The average patient will have spent several years dealing with inadequately effective medications before she or he is offered clozapine. To someone who has struggled with symptoms for so long, finally being on a truly effective medication certainly can feel miraculous.

通用形式的氯氮平在 1990 年代末上市。当一种药物作为仿制药上市时，制药公司就不再积极宣传它。专业期刊上不再有广告，会议上不再有宣传，也没有人来您的办公室帮忙解答问题。大约在同一时间，其他几种新的“第二代”或“非典型”药物进入市场，这些新药物得到了制造商的广泛推广。企业对氯氮平的宣传消失了，而对效果较差的新药的宣传却大行其道。你会认为医学院和培训精神科医生的项目会弥补这一不足。但这并没有全面发生。规定该国住院医师培训课程的国家组织并没有专门针对氯氮平的指导。特定培训计划是否提供针对氯氮平的培训取决于具体计划。这不是国家标准。因此，新的精神科医生完全有可能在没有第一手经验的情况下开出氯氮平处方并观察其通常显着的益处。如果没有这种经验，新任精神科医生可能会在没有准备好使用这种药物的情况下进入实践。精神科执业护士的情况也是如此。这些培训方面的差距造成了我所说的迷茫的一代临床医生，他们对使用氯氮平犹豫不决。

Not all schizophrenias are alike. Understanding that there are different kinds of schizophrenia helps to explain why clozapine appears uniquely effective. Most schizophrenias should probably be renamed “dopamine psychosis”. Scientists have shown that many people with schizophrenia have unusually high dopamine signals in key brain circuits. These findings explain why antipsychotic medications are effective. Most all of them are designed to adjust the elevated dopamine signals.

About two thirds of people with schizophrenia will have one of these high-dopamine forms of illness and will find relief from dopamine-adjusting medications. But there are other forms of schizophrenia where the dopamine signal appears entirely normal. A variety of neurochemical studies, including some recent PET scan work, has shown that people with these normal-dopamine schizophrenias don’t get much symptom relief from the first-line, dopamine-adjusting schizophrenia medications. This makes sense. Why would we expect that dopamine-focused medications would benefit someone without a high-dopamine brain? “Treatment-resistant schizophrenia” is the name that the field has sort of settled on to refer to the forms of schizophrenia that don’t respond to non-clozapine medications. This label is unfortunate, in my opinion, because it is both discouraging and misleading. The majority of so-called treatment-resistant cases actually respond beautifully to clozapine. It’s not that these illnesses were resistant to treatment. It’s that these folks have a normal-dopamine form of schizophrenia that won’t be served by dopamine-adjusting meds. Clozapine works in the majority of these schizophrenias because clozapine is not a dopamine-adjusting medication. Clozapine is the only thing we know of that works well for normal-dopamine schizophrenia.

可以测量人类的多巴胺信号，但这些技术在研究之外是不可用的。另一方面，药物反应模式可能是有用的指南。如果症状对多巴胺信号调节药物有反应，则精神病很可能属于高多巴胺类型。另一方面，如果尽管服用了足够剂量的多巴胺信号调节药物，症状仍没有太大改善，那么很可能是正常多巴胺精神病。注意药物反应是一种间接的方法，可以判断某人是否患有高多巴胺精神分裂症或正常多巴胺精神分裂症。

大多数人担心氯氮平可能会抑制白细胞计数。因为白细胞是抵御感染的第一道防线，它们数量的急剧减少会导致非常严重的感染。虽然白细胞计数的小幅下降相对常见，但大多数是暂时的且无关紧要的。氯氮平引起医学上严重的白细胞抑制实际上是罕见的（低于 1%）。由于经常测量白细胞计数，因此因这种抑制而感染的情况更为罕见。氯氮平最常见的严重医学并发症与便秘有关。在更严重的情况下，便秘会导致医疗紧急情况。重要的是要注意排便的频率，并在必要时服用药物以确保定期排便。在我职业生涯的大部分时间里，我一直是一名心理咨询师。我看到的患者仅部分受益于许多先前的治疗尝试。在我的职业生涯中，我可能已经看到了氯氮平的所有可能的副作用，但这是因为我主要与患有最复杂疾病的患者打交道。氯氮平的许多副作用可以通过不使用高剂量来预防，并通过注意停用一旦氯氮平达到治疗水平就不再需要的药物。体重增加是氯氮平的一个风险，但可以通过饮食和运动来最小化或预防，可能与促进体重减轻的药物如二甲双胍或利拉鲁肽结合使用。对于氯氮平的其他几种可能的副作用，也有类似的变通方法。知道要寻找什么可以及早发现潜在的严重副作用和及早干预以防止伤害。

Don’t delay. The research is clear: the longer someone experiences psychosis, the lower their prospects for long-term recovery. So, getting someone into remission as soon as possible is one of the most important goals in the care of individuals suffering from acute psychosis. Patients with recent-onset schizophrenia should go into remission (or be well on their way to remission) within no more than 8 months of treatment with antipsychotic medication (up to four months with medication #1, and up to four months with medication #2 if medication #1 failed to work). If delusions or hallucinations are not controlled by two different antipsychotic medications, the likelihood that the patient will respond to a third medication is minuscule, unless that medication is clozapine – where the response rate is more than 50%. Delaying the initiation of clozapine is equivalent to prolonging the duration of psychosis. And prolonged duration of psychosis has been shown to reduce quality of life in both the short-term and long-term.

许多人讨厌经常抽血，因此可能拒绝考虑使用氯氮平。局部麻醉药膏，用于麻痹抽血部位的皮肤，对于那些可能因为白细胞检测要求而不考虑使用氯氮平的人来说真的很有帮助。