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July 17, 2008 — 一项初期随机分派、双盲、安慰剂控制研究结果显示，olanzapine（Zyprexa，礼来药厂），一种用于治疗精神分裂症与双极性异常的非典型抗精神病药物，可能是罹患严重厌食症女性一个有效且安全的治疗。
来自于安大略渥太华健康医院、由Hany Bissada医师领导的研究团队发现，相较于安慰剂，olanzapine使体重增加的速度变快，比较早达到标准的身体质量指数，同时降低强迫症候群的速度也较快，两组间的不良反应并无显著差异。
Bissada医师向Medscape精神学与精神健康表示，我们需要更大型的研究，但无论如何，根据这些结果我们可以有信心地说，我们相信olanzapine是厌食症有效的起始治疗，截至目前，该疾病并没有稳定有效的药物。
这项研究发表于7月16日的美国精神医学期刊。
【最高的死亡率】
Bissada医师表示，厌食症是所有精神疾病中死亡率最高的，影响了约0.5%年龄介于15到24岁的女性，它因为最难以治疗而恶名昭彰。
治疗方式包括延长住院天数以稳定体重，合并精神谘询；以选择性血清素再回收抑制剂（SSRIs）以及标准安神药物治疗，并未被证实可以加速体重增加的速度、或是降低精神症状，包括忧郁、焦虑、身影扭曲、或是摆脱不了拒绝体重增加的感觉。
Bissada医师指出，针对olanzapine的主要原因是，罹患精神分裂症病患长期使用所观察到的体重增加。除此之外，该药物对双极性异常病患产生一种情绪调整作用，且被核准作为强迫症候群病患抗忧郁治疗的辅助疗法。
他表示，由于这个药物有许多有趣且吸引人的地方，因此我们决定进行这项随机分派研究。
【不良反应方面没有差异】
为了这项研究，研究者收纳34位确定罹患厌食症，且被转介至单一医院为主的日间饮食异常计划中的病患进行研究。
病患们被随机分派接受olanzapine或安慰剂，加上每天住院治疗，总共进行10周；这些药物以弹性剂量疗程方式处方，从最低剂量的2.5 mg，接着以每个星期2.5 mg缓慢地增加到最高剂量的每天10 mg。
这项研究的主要试验终点是药物对于体重增加作用，次级试验终点是针对其他精神症状的作用，包括焦虑、忧郁与强迫症。
Bissada医师表示，10周后，相较于安慰剂组，接受药物治疗组病患体重增加较多，且速度较快，研究结果在统计上有显著差异；此外，病患对于体重增加的厌恶感也明显降低。
当该药物有抗焦虑与抗忧郁的作用倾向时，这样的效果并未达到统计上的显著差异；Bissada医师表示，这可能是因为这项研究的收纳病患人数不足；此外，研究者们并未在两组之间发现不良反应的差异。
与olanzapine潜在相关的严重不良反应，包括体重增加过多、高血糖与糖尿病，这些与高剂量、长期治疗有关，短期较低剂量并未发生类似的问题。
他表示，在厌食症上，我们使用olanzapine暂时获得病患可以耐受进食且接受体重增加的主意。
【第一个反应通常是惊恐】
Bissada医师指出，以olanzapine治疗此疾病最大的挑战是让病患认同这项治疗；厌食症病患非常害怕体重增加，因此当提供他们会使体重增加的药物时，他们的第一个反应是惊恐。
他表示，你必须耐心地向他们解释，并再三向这些病患保证这个药物不会让他们过重，或是在一夜之间变得肥胖，同时要强调开给他们治疗厌食症的剂量比使用于精神分裂症的剂量低得多。
Bissada医师希望进行一个相似、但较大型的多中心研究，目前正在寻找合作伙伴；他表示，olanzapine可能值得使用于对治疗反应不佳的厌食症病患。
他指出，临床医师在治疗严重厌食症病患时，当病患拒绝进食，可能需要考虑提供这些病患使用较低的剂量（每天2.5至5 mg），及有病患可以随时停药的认知。
这项研究由礼来药厂经费赞助。作者表示没有相冲突的股份。
Atypical Antipsychotic May Be Safe, Effective Treatment for Anorexia Nervosa
By Caroline Cassels
Medscape Medical News
July 17, 2008 — Preliminary results from a randomized, double-blind, placebo-controlled trial suggest olanzapine (Zyprexa, Eli Lilly), an atypical antipsychotic used to treat schizophrenia and bipolar disorder, may be a safe, effective therapy for women with severe anorexia nervosa.
Led by Hany Bissada, MD, investigators at the Ottawa Health Hospital, in Ontario, found that compared with placebo, olanzapine resulted in a greater rate of increase in weight, earlier achievement of target body-mass index, and a greater rate of decrease in obsessive symptoms, with no difference in adverse effects between the 2 study groups.
"We need to do a much larger study, but nevertheless, based on these results, we can confidently say there is a reason to believe olanzapine may be useful in the initial treatment for anorexia nervosa, where to date, we've had no consistently successful drugs," Dr. Bissada told Medscape Psychiatry & Mental Health.
The study is published online July 16 in the American Journal of Psychiatry.
Highest Mortality Rate
Notoriously difficult to treat, anorexia nervosa has the highest mortality rate of all psychiatric disorders, affecting 0.5% of women aged 15 to 24 years, said Dr. Bissada.
Treatment consists of extended hospital stays to stabilize weight, as well as psychological counseling. Drug therapy with selective serotonin reuptake inhibitors (SSRIs) and standard neuroleptics have not been effective in increasing the rate of weight gain or reducing the psychological symptoms, including depression, anxiety, distorted body image, and obsessions that perpetuate resistance to weight gain.
One of the major reasons for looking at olanzapine in anorexia, said Dr. Bissada, was its observed long-term adverse effect of weight gain in patients with schizophrenia. Further, the drug produces a mood-modulating effect observed in bipolar patients and has also been used as adjunctive therapy to antidepressant treatment in patients with obsessive disorders.
"This was an interesting and attractive medication for many reasons, so we decided to conduct this randomized controlled trial," he said.
No Difference in Adverse Effects
For the study, the investigators recruited 34 female patients with confirmed anorexia nervosa who had been referred to a hospital-based daytime eating-disorders program at a single center.
Patients were randomly assigned to olanzapine or placebo, plus day hospital treatment, for a 10-week period. The drug was prescribed according to a flexible-dose regimen, starting at a minimum dose of 2.5 mg and titrated slowly by increments of 2.5 mg/week to a maximum dose of 10 mg/day.
The study's primary end point was the effect of the drug on weight gain. A secondary end point was to look at its impact on other psychological symptoms, including anxiety, depression, and obsessive/compulsive behavior.
After 10 weeks, patients in the active-treatment group gained more weight, at a faster rate, than those on placebo, a finding that was statistically significant, said Dr. Bissada. In addition, patients' obsession about weight gain was also significantly reduced.
While there was a trend toward antianxiety and antidepressant effects, this did not reach statistical significance. However, said Dr. Bissada, this may have been due to the small number of study subjects. In addition, the researchers found no difference in adverse effects between the 2 study groups.
Potentially serious adverse effects associated with olanzapine, including excessive weight gain, hyperglycemia, and diabetes, are linked to high-dose, long-term therapy and do not apply to short-term treatment with a smaller dose.
"In anorexia, we use olanzapine temporarily to get patients to a level where they can tolerate eating and accept the idea of weight gain," he said.
Panic Often First Reaction
One of the major challenges in treating this disease with olanzapine, said Dr. Bissada, is getting patients to agree to the therapy. "Anorexia nervosa patients are so afraid of weight gain that, when you offer them a medication that induces weight gain, their first reaction is panic.
"You have to be patient and explain and reassure these patients that this drug will not make them overweight or obese overnight and underscore the fact that the doses prescribed for anorexia are much, much smaller than doses prescribed for schizophrenia," he said.
Dr. Bissada hopes to conduct a similar, but much larger, multicenter trial and is currently looking for collaborators. In the meantime, he said, olanzapine may be worth a try in refractory anorexic patients.
"Clinicians treating patients with severe anorexia nervosa, who adamantly refuse to eat, may want to consider offering such patients a trial of this drug at a small dose (2.5 to 5 mg/day), with the understanding that the patient can stop it at any time," he said.
The study was supported by a grant from Eli Lilly. The authors report no competing interests.
Am J Psychiatry. Published online June 16, 2008. Abstract