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作者：Caroline Cassels  
出處：WebMD醫學新聞

　　January 5, 2010 — 當談及第2代抗精神病藥物(SGAs)的代謝效果監測時，顯示出醫師們並未注意政府或主要專業機構的建議。新研究認為，使用這些可能有明顯和嚴重代謝異常之藥物的病患，接受血糖或血脂檢測的人不到三分之一。
　　
　　研究者、科羅拉多大學的Elaine H. Morrato博士向Medscape Psychiatry表示，我們研究3個州的Medicaid保戶，發現使用SGAs之病患的糖尿病和血脂異常篩檢率低，並未遵照食品藥物管理局(FDA)之警訊或美國糖尿病協會與美國精神病協會的建議增加，當局和這些協會呼籲增加服用這些藥物之病患的代謝監測。
　　
　　這篇回溯分析登載於1月的一般精神醫學誌(Archives of General Psychiatry)。
　　
　　2003年後期，研究提出SGAs和增加高血脂與糖尿病風險之間有強烈關聯，FDA開始要求在olanzapine、fluoxetine、risperidone等SGAs藥物標籤上加註警語。
　　
　　研究作者們指出，有些案例中，高血糖相當嚴重，且與酮酸中毒、高滲透壓性昏迷或死亡有關。
　　
　　FDA也提議，要求SGAs的製造廠發出信函給神經精神健康照護專業人士，告知他們這些警訊，並建議他們須對有糖尿病診斷的病患、有糖尿病風險因素者、有高血糖症狀者進行葡萄糖檢測。
　　
　　同時，美國糖尿病協會與美國精神病協會發表共識聲明，提出與非典型抗精神病藥物有關的代謝風險，以及對所有服用這些藥物之病患的特定監測協定。
　　
　　【代謝檢測比率低】
　　為了評估這些警訊和建議對於葡萄糖及血脂檢測與SGAs藥物選用的影響，研究者檢視了加州、密蘇里州、奧勒岡州等3州的Medicaid保戶在2002至2005年間的檢驗資料。
　　
　　他們比較了109,451名使用SGAs之病患和203,527名開始使用albuterol但未服用抗精神病藥物之病患的代謝監測比率，也比較FDA提出警訊之前和之後的檢測比率。
　　
　　使用SGA治療之病患在開始時的葡萄糖和血脂檢測比率分別只有27%和10%，不過，FDA的警訊並未讓使用SGA治療病患的葡萄糖檢測比率增加，血脂檢測比率也只有略為增加1.7%。
　　
　　此外，使用SGA治療之病患的檢測比率和趨勢與albuterol對照組的病患沒有差異。
　　
　　Morrato博士表示，SGAs組病患和對照組的葡萄糖和血脂檢測比率竟然沒有差異，真是意料之外的發現，我本來認為，服用抗精神病藥物的病患會因為風險增加而使監測比率增加，但是並非如此。
　　
　　【傾向降低風險】
　　不過，研究者發現，代謝風險高於其他SGAs的olanzapine的新開立處方數減少，此外，代謝風險較低之aripiprazole的新開立處方數增加。
　　
　　然而，研究作者們指出，還不清楚這個改變是否因為在這段期間內加州取消了該藥物的核准。
　　
　　Morrato博士表示，我們觀察到，在SGA藥物的選用上有明顯改變，特別的是，我們發現代謝風險較高之藥物的使用減少，而風險較低的藥品使用增加。
　　
　　通常，我們在已經發表的文獻中看到的是，黑框警訊對於臨床實務的影響很小、甚至沒有影響。但是，我們這次發現醫師對於該風險有所警覺，而願意減少使用它，而不是用了它再增加監測，對我來說，這是未採用建議之外更值得探討的議題。
　　
　　【最省力的路徑？】
　　她推測，醫師們或許只是認為，相較於將例行的代謝監測整合到實務中，選用較低風險的製劑來降低病患的代謝風險比較簡單。
　　
　　她表示，改變選用的藥物比加入全新的複雜監測簡單許多，特別是心智健康體系和藥物健康體系之間如此不完整，你不可能到精神科醫師那邊抽血；心智健康執業者一般沒有這些設備。
　　
　　她指出，聽說有些醫師成功地將這些改變整合到他們的執業中，但是需要更廣泛地全面性的改變才可以表達此一日益增加的問題。
　　
　　她指出，SGAs的使用，不論是核准的適應症或非適應症都在增加，再者，這類製劑的使用對象也增加，納入了抗憂鬱藥物治療阻抗之憂鬱症輔助治療，孩童的使用也增加，最近的研究顯示，對於孩童的代謝副作用影響和成人一樣。
　　
　　Pfizer藥廠支持該研究。Morrato博士受聘於科羅拉多大學，與Pfizer藥廠簽訂合約進行本研究。 Morrato博士報告指出，她接受Eli Lilly和國家健康研究中心的研究資金，也擔任FDA的顧問。其他研究作者的宣告請見原始文獻。


Metabolic Monitoring in Patients Taking Second-Generation Antipsychotics Remains Poor

By Caroline Cassels
Medscape Medical News

January 5, 2010 — When it comes to monitoring metabolic effects of second-generation antipsychotics (SGAs), it appears that physicians are not heeding recommendations by government or leading professional organizations. New research suggests that less than one-third of patients treated with these medications, which can have significant and serious adverse metabolic effects, undergo blood glucose or lipid testing.

"We studied a 3 state population of Medicaid recipients and found diabetes and dyslipidemia screening among patients receiving SGAs was low and did not increase following the FDA [Food and Drug Administration] warnings or recommendations from the American Diabetes and American Psychiatric Associations, which called for increased metabolic monitoring of patients taking these agents," study investigator Elaine H. Morrato, DrPH, MPH, University of Colorado, Denver, told Medscape Psychiatry.

The retrospective analysis is published in the January issue of Archives of General Psychiatry.

In late 2003, prompted by research showing a strong link between SGAs and an increased risk for hyperglycemia and diabetes, the FDA began requiring warning labels on SGAs, including olanzapine, fluoxetine, and risperidone.

"In some cases the hyperglycemia was extreme and associated with ketoacidosis, hyperosmolar coma, or death," the study authors note.

As part of the FDA initiative, manufacturers of SGAs were required to send letters to neuropsychiatric health care professionals informing them of the warnings and advising them of the need for glucose testing in patients with a diagnosis of diabetes, risk factors for diabetes, or symptoms of hyperglycemia.

At the same time, the American Diabetes Association and the American Psychiatric Association published a consensus statement describing the metabolic risks associated with atypical antipsychotics and specifying a monitoring protocol for all patients receiving these medications.

Low Rates of Metabolic Testing

To assess the impact of these warnings and recommendations on glucose and lipid testing and drug selection of SGAs, the investigators examined laboratory claims data from the Medicaid population of 3 states — California, Missouri, and Oregon — between 2002 and 2005.

They compared rates of metabolic monitoring between a group of 109,451 patients receiving SGAs and a control group of 203,527 patients who began taking albuterol but who did not receive antipsychotic medication. Rates were also compared before and after the FDA warning.

Baseline glucose and lipid testing rates for SGA-treated patients were low at 27% and 10%, respectively. However, the FDA warning was not associated with an increase in glucose testing among SGA-treated patients, and lipid testing rates only increased by a marginal 1.7%.

In addition, testing rates and trends among SGA-treated patients were no different from those in the albuterol control group.

This finding was unexpected, said Dr. Morrato. "Glucose and lipid monitoring rates were no different for patients on SGAs than for the control group. I thought that given the increased risk that monitoring would be higher for patients taking antipsychotics, but this was not the case."

Intent to Reduce Risk

However, the researchers found that the number of new prescriptions for olanzapine, which has a higher metabolic risk than other SGAs, decreased. In addition, the number of new prescriptions for aripiprazole, which carries a lower metabolic risk, increased.

However, the study authors note that it is not clear whether this finding is attributable to the elimination of prior approval of the drug in California during the same time frame.

"We observed a significant change in SGA medication selection. Specifically, we saw a decrease in drugs with higher metabolic risk and an increased use of lower-risk agents.

"Often times we see in the published literature that black box warnings have little or no effect on clinical practice. But here we have a scenario where doctors are aware of the risk and are showing intent to decrease it, but not through increased monitoring. To me, this suggests there may be larger system issues that are inhibiting the adoption of the recommendations," said Dr. Morrato.

Path of Least Resistance?

She speculated that it may be simpler for physicians to lower their patients' metabolic risk by choosing lower-risk agents than for them to integrate regular metabolic monitoring into their practice.

"It is a lot easier to change your drug choice than it is to add in a whole new level of complexity to your practice, particularly since the mental health system and the medical health system are so fragmented. It's not like you can go to your psychiatrist and get your blood drawn; mental health practices generally just aren't set up that way," she said.

Anecdotally, she added, some clinicians have successfully integrated such changes into their practices, but widespread systemic changes are needed to address this growing problem.

She pointed out that use of SGAs, both for approved and off-label indications, is on the rise. Furthermore, the agents' target patient populations are expanding to include adjunctive treatment of antidepressant-resistant depression and use in an increasing number of children who, recent research suggests, are as vulnerable to the agents' adverse metabolic effects as their adult counterparts.

The study was supported by Pfizer Inc. Dr. Morrato is an employee of the University of Colorado, Denver, which was contracted by Pfizer Inc for this study. Dr. Morrato reports that she has received research funding from Eli Lilly and the National Institutes of Health and is a consultant to the FDA. The disclosures of the other study authors are available in the original article.

Arch Gen Psychiatry. 2010;67:17-24.