亨利·纳斯鲁拉博士
CURESZ 基金会科学总监

精神病复发的七大灾难性后果

It is very unfortunate when individuals with schizophrenia relapse repeatedly.  The #1 cause for the recurrence of psychosis is either inconsistent adherence to antipsychotic (AP) medications or total non-adherence (1).  The reasons for poor adherence in schizophrenia are related to the illness itself, and patients should not be blamed.

导致依从性 (2) 的精神分裂症症状包括：1) 失认症, or the lack of insight that one is very sick with delusions and hallucinations, leading to patient rejection of medication 2) 认知困难 包括严重的记忆障碍，导致忘记参加 AP，3) 阴性症状, including apathy, lack of motivation (avolition) and loss of the ability to do many things, including taking medications every day, 4) 多疑 AP 药物的常见副作用是中毒的证据，5) 酒精和药物使用 which are very common in persons with schizophrenia living in the community, and being intoxicated or stoned precludes taking prescription medication.  The combination of all those factors inevitably leads to a high rate of medication nonadherence after discharge from the first hospitalization.

就像 1 型糖尿病或高血压一样，必须每天服药否则有复发的风险，精神分裂症患者必须每天不间断地服用口服药。一项已发表的研究表明，AP 血液水平仅下降 25%（这意味着每 4 天缺少一次剂量）就足以导致精神分裂症复发 (3)。

Long-acting injectable (LAI) APs were developed in the 1970’s, precisely to solve the problem of non-adherence with oral medication.  However, due to the delay in scientific advances about the brain-damaging effects of psychosis (which appeared 3 decades later), clinicians back then were completely unaware that psychosis is associated with the dangers of recurring psychosis and resultant brain damage. They also believed that patients should “make their own decisions,” despite the well-known fact that the decision-making region of the brain (frontal lobe) is impaired in schizophrenia. Patients were even led to regard LAI treatment as “stigmatizing” and as a “punishment” for multiple relapses, so they resisted the LAIs. Now LAIs are regarded as a most compassionate and effective therapeutic approach to save patients with schizophrenia from psychosis-induced brain damage.

大约在 2000 年，精神病学神经科学研究表明，由于神经炎症和自由基 (5) 这两者都会损害灰质和白质，精神病会破坏脑组织并导致脑萎缩 (4)。每次精神病复发都会导致大脑结构和功能恶化。这可以防止患有精神分裂症的人恢复到首发精神病 (FEP) 之前的基线水平，这对于青春期后期或 20 岁出头的年轻人来说是非常悲惨的。

以下是由于依从性差导致的精神病反复发作 (6) 的 7 种灾难性后果：

  • 连接所有大脑区域并形成自我统一体的广泛的有髓纤维网络（约 137,000 英里）的脑组织丢失和脑萎缩以及解体。
  • Treatment-resistance patients respond to low doses of AP in the first-episode of psychosis (FEP) but need higher and higher dose with each psychotic relapse until eventually they become completely treatment-resistant (and will need Clozapine, which most patients never have access to). The brain structure deteriorates successively with each episode and that’s why APs that previously worked no longer do so.
  • 功能障碍，以及无法返回学校或大学或工作，无论患者在 FEP 之前做什么。因此，随着反复复发，这些年轻人变得完全残疾，而不是成为社会的生产性成员。
  • When individuals with schizophrenia become psychotic and behave erratically, sometimes they are killed by police, and many more are arrested and jailed, and often sentenced to prison. They no longer get admitted to state hospitals (because they have all been shuttered), and so are surrounded by armed guards instead of doctors, nurses and social workers who compassionately provide them with medical care instead of being thrown into a prison with murderers and rapists.
  • 许多人并没有意识到患有精神分裂症的年轻人在复发时的自杀率非常高。一些研究报告称，与普通人群中同龄年轻人相比，自杀死亡率高出 10,000% (7)。
  • Non-adherence can lead to drug abuse, a chaotic lifestyle and living on the sidewalks of large cities, with risk of becoming victims of crime.
  • Psychosis can cause unusual behavior, and poor dress and grooming, which intensify the public’s negative bias against serious mental illness.

然而，与这种令人沮丧的结果相反，精神分裂症患者却看到了希望和好消息。尽早使用 LAI，即在第一次住院后立即使用，可以在防止恶化方面产生巨大差异。有已发表的研究表明，如果开始 LAI，FEP 后第一年的复发率 650% 低于接受口服 AP 的患者的复发率 (8)。我个人有一些患者在改用可注射 AP 后连续 5 年没有复发。预防复发至关重要，因为最近的研究表明残疾实际上是在复发后开始的 第二, 不是精神病的第一集 (9)。因此，预防二次发作是精神分裂症缓解和康复的关键。因此，在精神分裂症首次住院后立即使用 LAI AP 可以预防大多数患者的精神分裂症恶化和恶化过程 (10)。

使用第二代 LAI 配方还有其他重要优势。 24 项已发表的研究报告称，它们 神经保护 （即帮助保持脑组织的完整性）（11）。此外，瑞典的一项为期 7 年的后续研究报告称，第二代 LAI 抗精神病药物与 最低死亡率 从所有原因（12）。鉴于精神分裂症的过早死亡率很高，这一点非常重要。

In summary, until a cure for schizophrenia is discovered, the best way to give patients a chance to return to their baseline and avoid the tragic, life-altering consequences, is to use second-generation LAIs immediately after discharge from the first hospitalization. Yet, inexplicably, this is rarely done, and 99% of clinicians in the country prescribe pills and do not use LAI APs for several years until patients have already relapsed several times.  By that time, the patients have already lost substantial amounts of brain tissue and have become disabled and criminalized and incarcerated.  Imagine how much different the landscape of schizophrenia would be if clinicians prevented any further episode of psychosis after the first one.  Many young people with a diagnosis of schizophrenia may be able to return to their baseline, further their education, get a job, get married, raise a family and exercise their constitutional right to pursue happiness (13).

亨利·A·纳斯鲁拉，

科学主任

参考：

  1. Valligan DI 等人： 患者更喜欢依从性 11:449-468, 2018
  2. 纳斯鲁拉哈： 目前的精神病学 16:4-7, 2017
  3. Subotnik KL 等人： 美国精神病学杂志 168:286-292, 2011
  4. Cahn W 等人： Arch Gen 精神病学 59:1002-1010, 2002
  5. Kohler-Torsberg O 等人： 精神病学前沿 11:1-3, 2020
  6. 纳斯鲁拉哈： 目前的精神病学 20:9-12, 2021
  7. Zaheer J 等人： 精神分裂症研究 222:282-38, 2020
  8. Subotnik KL 等人： 美国医学会精神病学 72:822-829, 2015
  9. Taipale H 等人： 柳叶刀精神病学 9:271-279, 2022
  10. 纳斯鲁拉哈： 目前的精神病学 21:6-9, 2022
  11. Chen AT 等人： 精神分裂症研究 208:1-7, 2019
  12. Taipale H 等人： 精神分裂症研究 197:274-280, 2018
  13. Nasrallah HA 等人： 目前的精神病学 20:14-16, 202