本帖最後由 goodcat1111 於 2009-4-5 08:26 編輯
作者：Caroline Cassels
出處：WebMD醫學新聞
March 9, 2009(夏威夷檀香山) — 一篇「額顳葉失智症(frontotemporal dementia，FTD)」病患的小型研究初步結果顯示，選擇性血清素再回收抑制劑(SSRI)citalopram可以有效降低此類病患的一些嚴重行為與心理症狀。
研究者發現，精神神經尺度(NPI)分數整體降低了50%，不過，更重要的或許是，這個為期6週的開放標籤研究顯示，藥物在NPI有關易怒與解除抑制的評量上，有相當大幅度的降低。
主要研究者、多倫多Sunnybrook健康科學中心的Nathan Herrmann醫師向Medscape Psychiatry表示，相較於其他行為介入方式，NPI分數減少50%是相當顯著的；但更重要的是，個別的NPI項目有更戲劇化的效果，該藥物顯示可以完全消除易怒與解除抑制症狀。
這些發現發表於美國老年精神科協會2009年會中。
【侵略與解除抑制的比率較高】
FTD有別於其他失智類型（包括阿茲海默氏症）的一個差異是，行為問題的比率相當高。Herrmann醫師表示，許多病患出現憂鬱、冷漠、侵略與解除抑制，使得這些病患的照護相當具有挑戰性。
此外，FTD比其他失智類型少見，且通常影響較年輕的人。
他表示，與AD不同的是，FTD不會影響腦部的膽鹼系統，但是對血清素系統有明顯影響，這也是檢視此類病患使用SSRI的另一個潛在因素。
他指出，再者，年長失智病患使用抗精神病藥物的安全顧慮，迫使我們極需建立安全有效的治療選項，以控制這些行為。
他指出，Citalopram被選用來進行此研究，因為它耐受良好，且很少有藥物交互作用，而這是治療年長病患的主要考量，因為他們有許多人服用多種藥物。
許多其他SSRI用於FTD的開放標籤與隨機控制試驗結果各有不同。不過，他表示，迄今並無針對citalopram的良好研究。
該研究包括了10名初次使用SSRI的FTD病患，平均年紀67歲。主要終點是NPI分數比開始時降低。次級終點包括額葉行為量表(Frontobehavioral Inventory，FBI)與康乃爾失智者憂鬱量表(Cornell Scale for Depression in Dementia，CSDD)。對藥物有反應則定義為NPI總分比開始時減少50%。
服用citalopram的病患調整到每天40mg之最大劑量治療6週，10名參與者中有6人有臨床顯著反應— 解除抑制與易怒都比開始時顯著減少。此外，Herrmann醫師表示，也有降低憂鬱的趨勢。
50%的研究對象出現副作用，體重減輕以及困倦是最常見的副作用。
【及時開始】
Herrmann醫師表示，雖然因為樣本少且為開放標籤設計而有限制，但結果是令人鼓舞的，且提供後續以大型隨機控制試驗研究的正面訊息。
他認為，這個結果比我們預期的更令人印象深刻，但是，這些只是開放標籤型研究的初步資料，因此可能有許多偏差；儘管如此，醫師對FTD病患嘗試此一方法時猶未晚。
Herrmann醫師表示，事實是，因為治療方向有限，而這是耐受良好的藥物，我不認為將其納入臨床實務考量為之過早，醫師在使用抗精神病藥之前，應先考慮使用citalopram這類藥物。
他指出，本研究屬於一個進行中的大型研究的一部份，此大型研究檢視神經內分泌標記，以及探討這些標記是否可以預測病患對SSRI的反應。
加拿大阿茲海默協會資助本研究。
美國老年精神科協會2009年會：摘要NR 28。發表於2009年3月6日。
Citalopram Reduces Severe Behavioral Symptoms in FTD
By Caroline Cassels
Medscape Medical News
March 9, 2009 (Honolulu, Hawaii) — Preliminary results from a small study of patients with frontotemporal dementia (FTD) indicates treatment with the selective serotonin-reuptake inhibitor (SSRI) citalopram may be effective in reducing some of the severe behavioral and psychological symptoms characteristic of this condition.
Researchers found an overall 50% reduction in scores on the neuropsychiatric inventory (NPI). However, perhaps more important, the 6-week, open-label study showed that the drug had a more dramatic reduction in NPI subscales that measure irritability and disinhibition.
"A 50% decline in NPI scores is very significant relative to some other behavioral interventions. But more important, there is an even more dramatic effect on individual items on the NPI, where the drug appears to completely wipe out symptoms of irritability and disinhibition," principal investigator Nathan Herrmann, MD, from Sunnybrook Health Sciences Centre, in Toronto, Ontario, told Medscape Psychiatry.
The findings were presented here at the American Association for Geriatric Psychiatry 2009 Annual Meeting.
Higher Rates of Aggression, Disinhibition
One of the things that differentiate FTD from other dementia types, including Alzheimer's disease (AD), is much higher rates of behavioral problems. Many patients present with depression, apathy, aggression, and disinhibition, which can make caring for these individuals very challenging, said Dr. Herrmann.
In addition, FTD is much less common than other types of dementia and tends to affect younger individuals.
Unlike AD, FTD does not affect the brain's cholinergic system but rather has a prominent effect on the serotonergic system, which is another potential reason to test the efficacy of SSRIs in this patient population, he said.
Further, he added, safety concerns over the use of antipsychotics in elderly patients with dementia have created an urgent need for safe and effective treatment options to control such behaviors.
Citalopram was chosen for the study, he said, because it is well tolerated and has very low drug-interaction rates, which is a major consideration when treating elderly patients, many of whom are taking a multitude of drugs.
A number of other open-label and randomized control trials of SSRIs have been studied in FTD with mixed results. However, he said, to date there have been no good studies looking at citalopram.
The study included 10 SSRI-naive FTD patients with an average age of 67 years. The primary end point was a reduction from baseline in NPI scores. Secondary end points included the Frontobehavioral Inventory (FBI) and the Cornell Scale for Depression in Dementia (CSDD). Response to medication was defined as a 50% reduction in NPI total score from baseline.
Participants received citalopram titrated to a maximum dose of 40 mg daily for 6 weeks. Six of 10 participants had a clinically significant response to the medication — with disinhibition and irritability significantly decreased from baseline. In addition, said Dr. Herrmann, there was a trend toward decreased depression.
Adverse events occurred in 50% of study subjects, with weight loss and drowsiness the most commonly reported adverse effects.
Not Too Early for Prime Time
While the study is limited by its small sample size and open-label design, said Dr. Herrmann, the results are encouraging and provide a signal of efficacy that warrants further study in a larger randomized controlled trial.
"I think the results were a little bit more impressive than we expected, but it is important to understand that these are preliminary data from an open-label study and as such, subject to many biases," he said.
Despite this, he added, it is probably not too early for clinicians to try this approach in FTD patients.
"The truth is, because there is so little in the way of treatment and this is such a well-tolerated medication, I don't think it's too early to consider using it in clinical practice, and physicians should consider using a drug like citalopram certainly before they consider using an antipsychotic," said Dr. Herrmann.
He added that this research is part of a larger, ongoing study that is examining neuroendocrine markers and whether such markers can predict patient response to SSRIs.
The study was funded by the Alzheimer's Society of Canada.
American Association for Geriatric Psychiatry 2009 Annual Meeting: Abstract NR 28. Presented March 6, 2009. |
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