單次輸注氯胺酮可迅速減少自殺念頭
資料來源:梅根.布魯克斯 / 2021 年 11 月 11 日 / Medscape 醫學新聞 / 財團法人台灣紅絲帶基金會編譯
新的研究顯示,單次輸注氯胺酮可迅速改善扭曲的思維和推理,以減少自殺念頭,而與藥物對嚴重抑鬱症的影響無關。
J.約翰.曼恩博士
紐約市哥倫比亞大學的資深作者 J. John Mann 醫學博士告訴 Medscape 醫學新聞:「以前的研究表明,氯胺酮可以迅速改善抑鬱症,這也是自殺意念迅速改善的部分原因」。
「尚不清楚還有哪些變化可以降低自殺意念和自殺行為的風險。這項研究確定了第二個新的改進領域——即可以潛在降低自殺風險的幾種認知功能的快速改善」,曼恩說。
該研究於 11 月 2 日於線上發表在《臨床精神病學雜誌》。
增強認知功能
共有 78 名患有重度抑鬱症和臨床上顯著的自殺意念的成年人在單次靜脈輸注氯胺酮或咪達唑侖(midazolam,註1) 的雙盲治療之前和之後 1 天接受了神經心理學測試。
作者報告說,與咪達唑侖相比,「氯胺酮對自殺意念和情緒產生了快速改善」。
氯胺酮與反應時間和認知控制/干擾處理的具體改善有關——這一措施與先前的抑鬱症自殺企圖有關。
使用咪達唑侖後自殺意念沒有緩解的患者亞組後來接受了非盲法氯胺酮治療並重新測試。在這些個體中,反應時間和認知控制/干擾處理也相對於氯胺酮前評估有所改善。
然而,研究人員指出,神經認知的改善與抑鬱、自殺念頭或一般情緒的變化無關。
儘管如此,他們說氯胺酮在治療後 1 天對神經認知有「積極的治療作用」,至少有一項與抑鬱症中的自殺行為相關的措施。
他們寫道,結果顯示「氯胺酮對有自殺行為風險的抑鬱症患者的治療具有額外的獨立治療作用」。
「氯胺酮調節許多神經遞質系統,包括對學習和記憶至關重要的谷氨酸傳遞。它增加了神經元之間突觸或連接的數量。這些效應是認知的基礎,也是對本研究中觀察到的有益效應的合乎邏輯的解釋」,曼恩告訴Medscape 醫學新聞。
「我們的研究幫助我們更好地了解氯胺酮如何在大腦中發揮作用,以及它可以多快改善扭曲的思維。能夠更清晰地思考可以讓某人感覺不那麼有自殺傾向」,研究調查員拉維說。哥倫比亞精神病學首席創新官 N. Shah 醫學博士在新聞發布會上說。
帶有注意事項的重要研究
紐約市西奈山抑鬱和焦慮發現和治療中心主任、醫學博士 James Murrough 發表評論說,這項研究很重要,並且「加深了對氯胺酮如何影響大腦系統和思維方式的理解。抑鬱症和自殺風險的背景」。
「這項研究意義重大的一個原因是,先前的研究顯示,在氯胺酮濫用和長時間暴露於高劑量的情況下,氯胺酮會對認知功能產生有害影響」,未參與該研究的 Murrough ,告訴 Medscape 醫學新聞。
「相比之下,在這項研究中,氯胺酮的單一低劑量治療可能會產生相反的效果,實際上至少在短期內會增強認知功能的一些標誌物」,他指出。
Murrough 說,這項研究的一個警告是,它只檢查了氯胺酮對認知的影響一次,即單次治療後 1 天。
「雖然這是一項重要的初步觀察,但我們尚不了解這種對認知的影響有多持久,或者這種觀察到的變化可能與氯胺酮對抑鬱症或自殺風險的任何益處有關」,默羅說。
「事實上,研究人員發現,氯胺酮後認知功能的變化與抑鬱或自殺想法的變化之間沒有關聯。與服用氯胺酮的患者相比,服用氯胺酮後認知功能有所改善的患者在情緒或自殺風險方面沒有差異。沒有顯示出認知的改善」,默羅指出。
「這提出了一個重要問題,即認知變化與氯胺酮潛在益處的相關性是什麼。這是一個重要領域,應該成為未來研究的重點,以改善抑鬱症患者和有患抑鬱症風險的患者的預後。自殺」,他補充說。
加拿大多倫多大學精神病學和藥理學教授、情緒障礙精神藥理學部門負責人、醫學博士 Roger McIntyre 也表示,這項研究「非常有趣,並且與他和他的同事之前的一些工作保持一致」完成顯示氯胺酮「似乎有益於認知方面,這是抑鬱症的核心因素」。
麥金太爾說:「這是一個可檢驗的假設,即現在報告和複制的認知改善可能在改善生活質量和透過這種治療發揮作用,並減少自殺率」。
這項研究得到了美國國家心理健康研究所的支持。 Mann 收到用於商業用途的哥倫比亞自殺嚴重程度評定量表的特許權使用費,該量表未在本研究中使用。 Murrough 的機構(西奈山)參與了涉及艾氯胺酮(Spravato)治療難治性抑鬱症的研究,並從艾氯胺酮製造商那裡獲得經濟報酬。 McIntyre 獲得了 CIHR/GACD/中國國家自然研究基金會的研究資助,以及 Lundbeck、Janssen、Purdue、Pfizer、Otsuka、Allergan、Takeda、Neurocrine、Sunovion、Eisai、Minerva、Intra-Cellular 和 Abbvie 的演講者/諮詢費.麥金太爾也是 AltMed 的首席執行官。
J Clin Psychiatry《臨床精神病學雜誌》。 2021 年 11 月 2 日線上發表。摘要
註1:咪達唑侖 (midazolam):咪達唑侖是一種苯二氮卓類藥物,用於麻醉、程序性鎮靜、睡眠障礙和嚴重躁動。它通過誘導嗜睡,減少焦慮,並導致喪失創造新記憶的能力而發揮作用。該藥物不會導致個人失去意識,只會使人鎮靜。它也有助於治療長期癲癇發作。 咪達唑侖可以口服、靜脈注射、肌肉注射、鼻腔噴灑或通過頰部給藥。
Single Infusion of Ketamine Rapidly Reduces Suicidal Thoughts
Megan Brooks / November 11, 2021
A single infusion of ketamine rapidly improves distorted thinking and reasoning to reduce suicidal thoughts, independent of the drug’s effect on severe depression, new research shows.
Dr J. John Mann
“Previously it was shown that ketamine rapidly improved depression and that explained part of the rapid improvement in suicidal ideation,” senior author J. John Mann, MD, with Columbia University in New York City, told Medscape Medical News.
“What was unclear was what else changed that could decrease suicidal ideation and the risk for suicidal behavior. This study identifies a second new domain of improvement — namely rapid improvement in several cognitive functions that can potentially reduce suicide risk,” said Mann.
The study was published online November 2 in the Journal of Clinical Psychiatry.
Boosts Cognitive Function
A total of 78 adults with major depressive disorder and clinically significant suicidal ideation underwent neuropsychological testing before, and 1 day after, double-blind treatment with a single intravenous infusion of ketamine or midazolam.
“Ketamine produced rapid improvement in suicidal ideation and mood” compared with midazolam, the authors report.
Ketamine was linked to specific improvement in reaction time and cognitive control/interference processing — a measure that has been associated with previous suicide attempt in depression.
A subgroup of patients whose suicidal ideation did not remit on midazolam were later treated with unblinded ketamine and retested. In these individuals, reaction time and cognitive control/interference processing also improved relative to pre-ketamine assessments.
Neurocognitive improvement, however, was not correlated with changes in depression, suicidal thinking, or general mood, the researchers note.
Nonetheless, they say ketamine had a “positive therapeutic effect” on neurocognition 1 day after treatment on at least one measure associated with suicidal behavior in the context of depression.
The results suggest “additional independent therapeutic effects for ketamine in the treatment of depressed patients at risk for suicidal behavior,” they write.
“Ketamine modulates many neurotransmitter systems including glutamate transmission which is crucial for learning and memory. It increases the number of synapses or connections between neurons. These effects are fundamental to cognition and are logical explanations of the beneficial effects observed in this study,” Mann told Medscape Medical News.
“Our study helped us gain a better understanding of how ketamine works in the brain and how quickly it can improve distorted thinking. Being able to think more clearly can make someone feel less suicidal,” study investigator Ravi. N. Shah, MD, chief innovation officer, Columbia Psychiatry, said in a news release.
Important Research With Caveats
Reached for comment, James Murrough, MD, PhD, director, Depression and Anxiety Center for Discovery and Treatment at Mount Sinai in New York City, said the study is important and “adds to a growing understanding of how ketamine affects brain systems and thinking in the context of depression and suicide risk.”
“One reason this study is significant is that prior studies have shown that ketamine can have harmful effects on cognitive functioning in the context of ketamine misuse and exposures to high doses for long periods of time,” Murrough, who wasn’t involved in the study, told Medscape Medical News.
“In contrast in this study, a single low-dose treatment of ketamine can have the opposite effects, actually boosting some markers of cognitive functioning, at least in the short-term,” he noted.
Murrough said one caveat to the study is that it only examined the effect of ketamine on cognition once, 1 day after a single treatment.
“While this is an important initial observation, we don’t yet have any understanding of how persistent this effect on cognition is, or how this observed change may be related to any benefit ketamine may have on depression or suicide risk,” Murrough said.
“In fact, the researchers found that there was no association between change in cognitive functioning following ketamine and change in depression or suicidal thinking. The patients who showed improved cognitive function following ketamine did not differ in terms of mood or suicide risk compared to patients who did not show an improvement in cognition,” Murrough noted.
“This raises the important question of what is the relevance of change in cognition to the potential benefits of ketamine. This is an important area and should be the focus of future research in order to improve outcomes for patients with depression and who are at risk for suicide,” he added.
Also weighing in, Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Canada, said the study is “very interesting and in keeping” with some previous work that he and his colleagues have done showing that ketamine “seems to benefit aspects of cognition which is a core element in depression.”
“It’s a testable hypothesis that the improvement in cognition now being reported and replicated could play some role in the improved quality of life and functioning with this treatment and as well reduce reducing suicide,” said McIntyre.
This study was supported by the National Institute of Mental Health. Mann receives royalties for commercial use of the Columbia-Suicide Severity Rating Scale, which was not used in this study. Murrough’s institution (Mount Sinai) was involved in research involving esketamine (Spravato) for treatment-resistant depression and receives financial remuneration from the manufacturer of esketamine. McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Allergan, Takeda, Neurocrine, Sunovion, Eisai, Minerva, Intra-Cellular, and Abbvie. McIntyre is also CEO of AltMed.
J Clin Psychiatry. Published online November 2, 2021. Abstract