新干预可改善无家可归精神病患者的结局

佛罗里达州好莱坞——一项小型前瞻性观察研究显示，包括采取定制化增强依从性措施和使用长效抗精神病注射剂的社会心理干预，可显著改善城市中无家可归的精神分裂症患者对口服药物的依从性、精神分裂症症状以及功能状态。

美国凯斯西储大学的Martha Sajatovic博士在由美国国立精神卫生研究所主办的临床新药评价单元会议上报告称，不仅如此，这种干预还改善了患者的居住条件，而这是通常精神分裂症研究中不太关注的，对于患者及其家人而言却是最实际的问题之一。

居住条件不佳——住在室外或监狱——的时间，由参加研究之前6个月的56%，下降至干预头3个月的41%，在干预3~6个月期间进一步降至14%。“我认为关于居住条件的数据是本项研究中最有趣的，因为事实上我们并未施加任何与居住条件有关的干预。”

定制化增强依从性措施(CAE)是由Sajatovic博士及其同事设计的，以需求为出发点、灵活确定药物剂量的社会心理干预手段，最初用于提高接受抗精神病治疗的双相障碍患者对药物治疗的依从性。一项随访6个月的研究表明CAE对这一患者群有益(Bipolar Disord. 2012;14:291-300)，随后Sajatovic博士等人便将经过改良的CAE用于一个尤其难以处理的患者群：患有精神分裂症/分裂情感障碍、对医生开具的口服抗精神病药物依从性差的无家可归患者。


Martha Sajatovic博士

这项为期6个月的观察性非对照研究纳入了30例无家可归的精神分裂症患者。这些患者的平均年龄为42岁，大约半数为女性，97%有物质滥用史，97%曾被关押。大多数患者尚未读完高中，70%为单身或从未结过婚。

CAE的内容包括：针对基线时确定的导致依从性差的关键因素，每月进行1次简短干预；开展个体化心理教育；采取改良的动机增强治疗；指导其与医务人员沟通日常生活与治疗事宜。

在开展每月1次的CEA时，还会对患者注射1剂长效抗精神病药物。由于这项研究是由一家小型非营利性慈善机构资助的，研究者选用了最便宜的长效抗精神病药物——癸酸氟哌啶醇肌内注射剂。该药的副作用较强，最明显的是40%的患者因失静症而显得坐立不安，33%的患者口干，33%的患者肌肉颤搐。24周时，平均每月给药剂量为68 mg，范围为50~100 mg。

结果显示，所有患者均在每月注射长效抗精神病药物的同时坚持使用口服药物。在6个月干预期间，患者对口服药物的依从性急剧上升：基线时，患者在参加研究前1个月内漏服了46%的口服药物，而在25周后漏服率仅为10%。患者对长效注射剂治疗的依从性也较为理想：6个月时依从率为76%。

患者在多个指标上表现出明显进步：依从行为、治疗态度、精神症状和功能状态等(见表)。



在这30例患者中，有20例完成了6个月研究。在10例未完成研究的患者中，3例被收押，2例搬到别处居住，1例因药物引起的失静症而停药，4例失随访。

Sajatovic博士指出：“本项研究对我们的最大启示在于，当考虑依从性时，我们可能会想到复发，然而在此类患者中很难将复发当做一个结局指标，因为复发只是第一步。因此我们还得考虑患者及其家人真正看重的结局指标，例如功能状态和居住条件。”

特邀评论员、加州大学洛杉矶分校神经精神研究所的Stephen R. Marder博士赞同这一观点：“依从性本身并不一定是目标，而是通往更佳结局的路径。关注一些与复发和症状关系不大的事物——例如居住条件——有一些优势。我们需要告诉患者，预防复发只是提高依从性的原因之一，依从性较好的患者似乎具有更好的居住、工作、学业或独立生活等长期结局。有了依从性才能开始康复。”

Marder博士担任多家药企的顾问或获得其提供的研究资助。Sajatovic博士报告称无相关利益冲突。

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By: BRUCE JANCIN, Internal Medicine News Digital Network

HOLLYWOOD, FLA. – A manualized psychosocial intervention known as customized adherence enhancement coupled with long-acting injectable antipsychotic medication produced marked improvement in adherence to concomitant oral medication as well as in psychiatric symptoms and functional status in urban homeless people with schizophrenia in a small prospective observational study.

Moreover, the intervention also achieved an impressive improvement in a domain not often considered in psychiatric studies, but one of great practical value to patients and their families: housing conditions, Dr. Martha Sajatovic said at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.

The mean time spent in suboptimal housing – living outdoors or in jail – changed from 56% during the 6 months prior to study enrollment to 41% in the first 3 months of the intervention and a mere 14% in the second 3 months of the study, reported Dr. Sajatovic, professor of psychiatry and neurology at Case Western Reserve University, Cleveland.

"What I think is most interesting about our study are the housing data. Our intervention did not include anything about housing – no housing placement or outreach or anything like that. People used whatever was available in the community. And Cleveland has the dubious distinction of being one of the poorest cities in America, so we have services, but not a lot of them," she noted.

Customized adherence enhancement (CAE) is a needs-based, flexibly dosed psychosocial intervention originally developed by Dr. Sajatovic and her colleagues to improve medication adherence in individuals with bipolar disorder receiving antipsychotic therapy. Following a 6-month study demonstrating its benefits in this population (Bipolar Disord. 2012;14:291-300), the investigators adapted the manualized CAE program for application in a particularly challenging patient population: homeless people with schizophrenia/schizoaffective disorder and poor adherence to their prescribed oral antipsychotic medication.

This 6-month, observational, uncontrolled study involved 30 homeless schizophrenic patients. The CAE consisted of once-monthly brief interventions matched to core adherence vulnerabilities identified at baseline. The CAE entailed psychoeducation, modified motivational enhancement therapy, and coaching on communication with providers and medication routines.

At the time of the monthly CAE session, patients also received a dose of long-acting injectable antipsychotic medication. Because the study was funded by a small nonprofit charitable organization, investigators employed the least expensive long-acting antipsychotic available: intramuscular haloperidol decanoate. This resulted in a high rate of side effects, most prominently restlessness because of akathisia in 40% of subjects, dry mouth in 33%, and muscle twitching in 33%. The mean monthly dose at 24 weeks was 68 mg, with a range of 50-100 mg.

The study population was typical of homeless individuals with major mental illness. Their mean age was 42 years, roughly half were women, 97% had a history of substance abuse, 97% had a history of incarceration, most subjects had not finished high school, and 70% were single or never married.

All patients remained on oral medication in addition to their new long-acting injectable antipsychotic regimen. Adherence to oral medication improved dramatically during the 6-month intervention: At baseline, patients had missed 46% of their oral medication during the past month, compared with just 10% at week 25. Adherence to long-acting injectable therapy was good: 76% at 6 months.

Twenty of 30 patients completed the 6-month study. Of the 10 nonfinishers, 3 were incarcerated, 2 relocated elsewhere, 1 discontinued because of drug-induced akathisia, and 4 were lost to follow-up.

Participants showed significant improvement in numerous measures of adherence behavior, treatment attitudes, psychiatric symptoms, and functioning (see chart).

For Dr. Sajatovic, the take-home message from this study was clear: "I would say that when we think about adherence, we can talk about relapse, but it’s very hard to have relapse as an outcome measure in these kinds of patients. They start out in relapse. So we should also consider those outcome components that patients and families really value, like functioning and housing."

Discussant Dr. Stephen R. Marder concurred: "Adherence is not necessarily the goal; it’s the path to better outcomes. And looking at things that are distal to relapse and symptoms – things like housing – shows an advantage. We need to tell patients that preventing relapse is just one of the reasons to be adherent. Long-term outcomes, whether it’s housing, work, school, or independent living, seem to be better for people who are adherent to medication. With adherence, rehabilitation can start.

"Without adherence, it’s really impossible to do," commented Dr. Marder, professor of psychiatry and behavioral sciences and director of the section on psychosis at the University of California, Los Angeles, Neuropsychiatric Institute.

He serves as a consultant to or recipient of research funding from roughly a dozen pharmaceutical companies. Dr. Sajatovic reported having no conflicts of interest.