SSRI可作為中風後的重建治療

作者：Caroline Cassels  
出處：WebMD醫學新聞

　　February 5, 2010 — 選擇性血清素再吸收抑制劑(SSRI)escitalopram顯示可以促進中風之後的認知恢復，這類藥物或許可以有效地運用於此類病患的重建治療。
　　
　　愛荷華大學的研究者進行的一篇隨機控制試驗顯示，相較於使用安慰劑或者接受問題解決治療(PST)者，使用相對低劑量escitalopram的非憂鬱症中風病患，整體認知功能有所改善，特別是文字和視覺記憶功能。
　　
　　主要研究者Ricardo Jorge醫師向Medscape Psychiatry表示，本研究重要之處在於，我們可能可以增加中風病患的恢復－這是資源有限的臨床領域。
　　
　　Jorge醫師指出，不過，我們還未證明果真如此，因此，雖然結果顯示有效，仍需要以更大型的研究來證實。
　　
　　這項研究登載於2月的一般精神醫學誌(Archives of General Psychiatry)。
　　
　　【重建治療的好處增加】
　　根據Jorge醫師表示，中風之後幾個月內給予重建治療的好處越來越多，這段期間的自發性動作與認知恢復程度最大。
　　
　　Jorge醫師表示，雖然血栓溶解治療在中風治療方面有明顯進步，但它的效果有限，因為它必須在症狀發生之後的幾小時內給藥。
　　
　　Jorge醫師表示，這表示，並非所有的中風病患都以這些製劑治療，事實上，在美國，只有少數中風病患接受血栓溶解治療，所以我們希望探討用於次急性與慢性期中風恢復的輔助恢復方式，以便可以延長治療時機。
　　
　　研究作者們寫道，有一類研究聚焦在抗憂鬱藥物，且強烈認為抗憂鬱藥物透過複雜的訊息串聯，增加神經營養因子的表現、神經細胞與神經膠細胞增生、增加軸突分枝、產生新的突觸等，而發揮它們的治療效果。
　　
　　【促進神經可塑性】
　　中風之後，隨即有一段自發性恢復期，腦部重新組織其網絡，試圖重建因為缺血而損傷的區域。
　　
　　他表示，我們希望探討，安全的藥物介入是否有助於這個重建過程。我們知道抗憂鬱藥物的效果，包括它們對心情的效果，或許與神經可塑性有關，例如，增加神經營養因子值；因此，可以據以提出「抗憂鬱藥物用於非憂鬱症的中風病患可以加強恢復過程」的這個假設。
　　
　　為了檢視escitalopram對於認知結果的影響，研究者比較此藥與安慰劑和PST。
　　
　　該研究包括了於2003年7月9日至2007年10月1日在愛荷華大學檢查的129名無憂鬱症的中風病患。 為了進行12個月的試驗，病患們在出血性或缺血性中風之後3個月內，被隨機指派到三個治療組之一。
　　
　　這些病患中，43人隨機分派到每天服用5-10 mg的escitalopram，45人每天服用安慰劑，41人到接受PST的非雙盲組。
　　
　　研究結果的測量包括神經心理狀態評估之重複型量表(Repeatable Battery for the Assessment of Neuropsychological Status[RBANS])、軌跡描繪、語意流暢測驗、Wechsler氏成人智力量表第三版(Wechsler Adult Intelligence Scale III)以及叫色測驗等，從開始到治療結束時的改變。
　　
　　【獨立生活】
　　結果發現，escitalopram對於改變RBANS總分以及RBANS延遲記憶分數的改變有顯著的效果。
　　
　　研究者也指出，相較於其他兩組，escitalopram組的研究對象在日常生活比較可能會有改善。
　　
　　再者，研究顯示，安慰劑組病患比escitalopram組病患更可能生活在較有組織的環境，不過，這個差異未達統計上的顯著程度。
　　
　　Jorge醫師表示，研究者選擇escitalopram進行研究是因為它可接受的安全性與副作用資料，事實上，相較於其他SSRIs，它對於血清素系統比較有選擇性。
　　
　　Jorge醫師表示，雖然研究發現是正面的，在改變中風病患的治療協定之前，還需要更多研究。
　　
　　Jorge醫師表示，重建治療是極待探索的重要領域，我們希望進行類似而更大型的研究，每一組至少有300到400名病患，如果可以證明這些結果，我們就可以開始考慮將這個加入中風病患的治療，不論是單用或者併用選擇性復建治療。
　　
　　國家心智健康研究中心支持本研究，Jorge醫師報告接受兩筆旅行費用以參加Hamilton Pharmaceutical Company與Avanir Pharmaceutical Company這兩家公司的全國會議。其他作者們的宣告請見原始報告。


SSRI Shows Promise as Restorative Therapy Following Stroke

By Caroline Cassels
Medscape Medical News

February 5, 2010 — The selective serotonin reuptake inhibitor (SSRI) escitalopram appears to enhance cognitive recovery following stroke, suggesting this class of medications may be an effective restorative therapy for this patient population.

A randomized controlled trial conducted by investigators at the University of Iowa in Iowa City shows that nondepressed stroke patients who received relatively low doses of escitalopram experienced an improvement in global cognitive functioning, specifically in verbal and visual memory functions, compared with their counterparts who received placebo or who underwent problem solving therapy (PST).

"This study is important in the sense that it suggests that we may be able to increase the recovery of stroke patients — a clinical area where there are limited resources," principal investigator Ricardo Jorge, MD, told Medscape Psychiatry.

"However," Dr. Jorge added, "we have not yet proven that this is the case, and, therefore, while the results are quite promising, they merit replication in a larger patient population."

The study is published in the February issue of Archives of General Psychiatry.

Growing Interest in Restorative Therapies

According to Dr. Jorge, there is growing interest in restorative therapies that can be administered during the first few months following stroke — a period when the greatest degree of spontaneous recovery of motor and cognitive deficits occurs.

Although thrombolytic therapy has been a boon to stroke treatment, said Dr. Jorge, its efficacy is limited because it must be administered within the first few hours of symptom onset.

"This means that not all stroke patients are treated with these agents. In fact, in the United States, only a minority of [stroke] patients receive thrombolytic therapy. So we are interested in exploring ways of assisting recovery in the subacute and chronic phases of stroke recovery which offer us a more prolonged therapeutic window," said Dr. Jorge.

One line of research has focused on antidepressant medications and "strongly suggests that antidepressants exert their therapeutic effects through complex signaling cascades that result in the increased expression of neurotrophic factors, the proliferation of neural and glial cell precursors, increased axonal sprouting, and the development of new synapses," the study authors write.

Enhancing Neuroplasticity

Immediately following stroke there is a period of spontaneous recovery where the brain reorganizes its networks in an attempt to compensate for deficits in areas damaged by ischemic injury.

"We wanted to investigate whether a safe pharmacological intervention would help this process of reorganization. We know antidepressants, and in fact even the antidepressant effect of these medications, aid neuroplasticity by, for example, increasing the level of neurotrophic factors. So this makes possible the hypothesis that antidepressants in nondepressed stroke patients could possibly augment this recovery process," he said.

To examine the effects of escitalopram on cognitive outcomes, the investigators compared the drug to placebo and PST.

The study included 129 nondepressed stroke patients examined at the University of Iowa Stroke Center from July 9, 2003, to October 1, 2007. For the 12-month trial, patients were randomly assigned to 1 of the 3 treatment arms within 3 months following either a hemorrhagic or ischemic stroke.

Of these individuals, 43 were randomized to receive 5 to 10 mg of escitalopram daily, 45 to receive a daily placebo, and 41 to the nonblinded arm of PST.

The study's outcome measures included changes in scores from baseline to the end of treatment for the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail Making, controlled Oral Word Association, Wechsler Adult Intelligence Scale III, and Stroop tests.

Independent Living

The results revealed a significant effect of escitalopram treatment on change in RBANS total score and the change in RBANS delayed memory score.

The researchers also note that participants in the escitalopram group were significantly more likely to live independently compared with subjects in the other 2 groups.

Further, the study showed that patients receiving placebo were more likely than those receiving escitalopram to live in a more structured environment. However, the difference was not statistically significant.

Dr. Jorge said the investigators chose escitalopram for the study because of its favorable safety and side effect profile and the fact that it has a more selective effect on the serotonin system than other SSRIs.

Although the study findings are positive, Dr. Jorge said more study is needed before altering treatment protocols in stroke patients is warranted.

"Restorative therapies are an important area to explore. We are hoping to conduct a similar but much larger study with at least 300 to 400 patients in each arm, and if we can replicate these results, then we can start thinking about adding this treatment — either alone or in combination with select rehab therapy — in stroke patients," said Dr. Jorge.

The study was supported by the National Institute of Mental Health. Dr. Jorge reports receiving 2 travel awards to participate in national meetings from the former Hamilton Pharmaceutical Company and Avanir Pharmaceutical Company. Disclosures of the other study authors can be found in the original paper.

Arch Gen Psychiatry. 2010;67:187-196.