抗精神病药物的代谢监测仍然重要

芝加哥——在第二代抗精神病药物治疗期间，监测患者的代谢不良反应仍然是一大临床挑战，尽管相关的监测推荐意见已经发布将近10年了。

在2013年精神病学进展会议上，美国佛罗里达大学精神病学教授、北佛罗里达/南乔治亚退伍军人健康系统的Rajiv Tandon博士说：“在与精神科医生谈论这个问题时，几乎每位医生都知道监测的必要性，但遗憾的是，实际上监测工作远远没有跟上。”

第二代抗精神病药物导致糖尿病、高血压、高脂血症等代谢后果的几率是比较高的，有研究显示在精神分裂症患者中这些代谢后果的总发生率超过了50%。此外，在美国抗精神病药物的使用率和糖尿病的患病率都呈现出上升趋势。具有里程碑意义的CATIE (临床抗精神病药物干预效果试验)研究表明，糖尿病的不治疗率约为30%，高血压为62.4%，而高脂血症则高达88%(Schizophr. Res. 2006;86:15-22)。

Tandon博士指出，影响精神科医生开展监测工作的阻碍因素包括时间有限、当患者没有初级保健医生时不知道如何处理、患者依从/费用报销等问题。鉴于大部分精神科医生都认为很难自信地开展代谢监测工作，Tandon博士建议他们把时间和精力用在建立与初级保健医生的关系上。

Tandon博士说：“在我所工作的退伍军人事务部，就这个问题而言我实际上把大部分的精力都用在了与初级保健医生的沟通上，尽量帮助他们了解这个问题的严重性，我们为什么需要一起合作来帮助患者等等。”“现在我还没有做得特别成功；我能做的是先让他们听我说。这需要时间，但很有价值。”

好消息是退伍军人事务部每年都会拨款6千万美元用于接受第二代抗精神病药物治疗的退伍军人的代谢监测。Tandon博士也承认，坏消息是奇怪的是现在这类患者的代谢结局也只是略有改善。

但他仍然建议精神科医生针对接受抗精神病药物治疗的所有患者，分别在治疗开始时、治疗90天后以及之后每年监测1次代谢情况。对于高危患者，比如存在胰岛素抵抗的患者，则可能需要增加监测频率。此外，医生还应尽量选用那些导致代谢并发症风险最小的抗精神病药物，避免多重用药，部分患者也可以考虑采用二甲双胍等辅助治疗，生活方式调整以及患者教育也很重要。

一项纳入了128例在接受抗精神病药物治疗期间体重增加超过10%的首发精神分裂症患者的研究表明，二甲双胍750 mg/d加生活方式干预12周优于单纯生活方式干预，体重指数平均下降1.8 kg/m²，胰岛素抵抗指数平均下降3.6，腰围平均减少2 cm(JAMA 2008;299:185-93)。

未来，基因变异分析可能有助于揭示精神分裂症与糖尿病之间的交互作用，并且发现潜在的药物靶点。近期开展的一项研究就找到了33个与精神分裂症和2型糖尿病都显著相关的易感基因，其中12个与肿瘤坏死因子相关，4个与v-akt鼠胸腺瘤病毒致癌基因同源物1(AKT1)相关(BMC Med. Genomics 2013;6 Suppl. 1:S17)。

Tandon博士声明是世界精神病学协会药物精神病学分会的成员。这次会议由Current Psychiatry和美国临床精神科医师协会资助。Current Psychiatry和这家新闻机构属于同一家母公司。

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By: PATRICE WENDLING, Internal Medicine News Digital Network

CHICAGO – Monitoring patients on second-generation antipsychotic medications for metabolic adverse effects continues to be a clinical challenge, nearly a decade after monitoring recommendations came out.

"After that, if you talked to psychiatrists, almost everyone was aware of the issue and the need to monitor, but the monitoring unfortunately has not caught up," Dr. Rajiv Tandon said at Psychiatry Update 2013.

The consequences are high for patients on second-generation antipsychotics, with metabolic disorders such as diabetes, hypertension, and hyperlipidemia collectively exceeding 50% in some studies of patients with schizophrenia. Moreover, antipsychotic use and diabetes are both rising among Americans. Yet, in the landmark CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study, rates of nontreatment ranged from 30% for diabetes to 62.4% for hypertension and 88% for dyslipidemia (Schizophr. Res. 2006;86:15-22).

Barriers to monitoring for psychiatrists include a lack of time, not knowing what to do with the information when their patient lacks a primary care provider, and patient compliance/reimbursement issues, said Dr. Tandon, of the North Florida/South Georgia Veterans Health System in Gainesville, Fla.

Given that monitoring is such a difficult task for most psychiatrists to take on and do confidently, he suggests they devote the time and effort to cultivating relationships with primary care providers.

"At the VA [Veterans Affairs department] where I work, the place where I’m spending most of my effort with regard to this problem is actually with primary care, trying to help them understand how serious this issue is and why we have to work together in order to help our patients," said Dr. Tandon, who also is a professor of psychiatry at the University of Florida in Gainesville.

"I’ve not been particularly successful thus far; all I’ve been able to accomplish is to get them to listen. It takes time, but it’s well worth it."

The good news is that the Department of Veterans Affairs is spending $60 million annually on metabolic monitoring of veterans on second-generation antipsychotics. The bad news is that anecdotally, metabolic outcomes are only modestly better, Dr. Tandon acknowledged.

Still, he recommends that psychiatrists monitor all their patients on antipsychotics at the start of treatment, at 90 days, and annually thereafter. Monitoring frequency might need to be stepped up in higher-risk patients, such as those with insulin resistance.

Providers also should start patients on an antipsychotic least likely to cause metabolic complications, avoid polypharmacy, and consider adjunctive treatments like metformin in some patients and also lifestyle interventions in combination with patient education.

In a study of 128 adults with first-episode schizophrenia who gained more than 10% of their weight on antipsychotics, 12 weeks of metformin 750 mg/day and lifestyle intervention was superior to either intervention alone, decreasing body mass index on average by 1.8 kg/m2, insulin resistance index by 3.6, and waist circumference by 2 cm (JAMA 2008;299:185-93).

In the future, genetic alterations might help unravel the cross talk between schizophrenia and diabetes, and lead to candidates for drug targets. A recent study identified 33 highly significant susceptibility genes linked to both schizophrenia and type 2 diabetes, including 12 related to tumor necrosis factor and 4 to v-akt murine thymoma viral oncogene homolog 1 (AKT1) (BMC Med. Genomics 2013;6 Suppl. 1:S17).

Dr. Tandon disclosed that he is a member of the World Psychiatry Association Pharmacopsychiatry section. The meeting was sponsored by Current Psychiatry and the American Academy of Clinical Psychiatrists. Current Psychiatry and this news organization are owned by the same parent company.