氯胺酮 (Ketamine) 與電痙攣療法(ECT) 治療抑鬱症：首次正面交鋒結果

梅根.布魯克斯 / 2022 年 1 月 28 日 / Medscape Medical News / 財團法人台灣紅絲帶基金會編譯

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新的研究顯示，靜脈注射氯胺酮可有效治療抑鬱症，但不如電痙攣療法 (ECT)。

在第一次正面對決的試驗中，ECT 在住院的重度抑鬱症患者中比靜脈注射氯胺酮更有效，緩解率更高，症狀減輕更大。

然而，研究人員指出，氯胺酮導致近一半的參與者得到緩解，並且是治療嚴重抑鬱症的「有價值」選擇，特別是在年輕患者中。

氯胺酮輸注的高緩解率「顯示它絕對可以在臨床環境中使用，但與氯胺酮相比，患者使用 ECT 獲得緩解的可能性更大」，首席研究員 Pouya Movahed Rad 醫學博士（藥理學)，瑞典隆德大學精神病學高級顧問和研究員告訴 Medscape 醫學新聞。

KetECT 研究的結果最近於線上發表在《國際神經精神藥理學雜誌》上。

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主要關注緩解

平行、開放標籤 (open-label)、非劣效性研究包括 186 名 18-85 歲的患者，這些患者因嚴重的單相抑鬱住院並且在蒙哥馬利-埃斯伯格抑鬱評定量表 (MADRS) 上得分至少為 20。

參與者被隨機分配（1:1）每週三次輸注外消旋氯胺酮（0.5 mg/kg，超過 40 分鐘）或 ECT。所有患者在研究期間繼續服用抗抑鬱藥物。主要結果是緩解，定義為 MADRS 評分為 10 分或更低。

結果顯示，ECT 組的緩解率顯著高於氯胺酮組（分別為 63% 和 46%；P = .026）。緩解率差異的 95% 信賴區間估計在 2% 和 30% 之間。

氯胺酮和 ECT 都需要中位數 6 次治療來誘導緩解。

年齡是研究結果的一個因素。在 ECT 組中，與年輕患者（18-50 歲）相比，老年患者（51-85 歲）的緩解率明顯更高，緩解率分別為 77% 和 50%。

但氯胺酮組的情況正好相反，年輕患者的緩解率明顯高於老年患者（61% 對 37%）。

研究結果還支持氯胺酮治療精神病性抑鬱症患者的安全性和有效性，ECT 組 15% 的患者和氯胺酮組 18% 的患者存在這種情況。

在該亞組中，一半的精神病性抑鬱症患者在使用氯胺酮後症狀緩解，沒有跡象顯示這些患者有特別的不良反應。 ECT 的緩解率為 79%。

在 12 個月的追蹤期間，在 ECT 組和氯胺酮組中，匯款人的複發率相似，分別為 64% 和 70%（對-等級檢定 P = .44）。

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讓病人決定

正如預期的那樣，ECT 和氯胺酮具有不同的副作用特徵。 ECT 更常見長期健忘症，氯胺酮更常見解離性副作用、焦慮、視力模糊、欣快、眩暈和復視（複視）的報告。

「正如預期的那樣，在氯胺酮治療期間觀察到分離症狀，但它們是短暫的，在大多數情況下是輕微且可以忍受的」，Movahed Rad 說。

研究人員指出，參與的研究地點都有長期使用 ECT 的經驗，但沒有使用氯胺酮的經驗。

「工作人員和一些患者熟悉 ECT 常見的副作用，但對氯胺酮的不良心理影響準備不足。這，並且知道 ECT 在研究後可用，可能導致氯胺酮組的流失率較高」，他們寫道。

如果 ECT 和氯胺酮都可用，「當然，在選擇治療時應考慮患者的偏好」，Movahed Rad 說。

「如果 ECT 無法取得，則應提供氯胺酮。抑或由於麻醉或其他軀體風險因素的過度風險則避免給予氯胺酮。對 ECT 沒有反應抑或有不可接受的副作用的患者應提供氯胺酮輸注且反之亦然」，他加上說明。

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一個很好的替代選擇

加拿大多倫多大學精神病學和藥理學教授 Roger McIntyre 醫學博士在評論 Medscape 醫學新聞的研究結果時說，數據證實 ECT 對難治性抑鬱症非常有效，並顯示「新人」靜脈注射氯胺酮也有「非常好」。

「這是一項極其重要的研究，它真正確定了氯胺酮在非常難以治療的人群中的功效」，未參與該研究的麥金太爾補充道。

McIntyre 補充說，這項「嚴謹、精心設計的研究解決了一個關鍵問題」，即 ECT 和靜脈注射氯胺酮的比較療效。它還「對氯胺酮對年輕人的療效做出了強有力的聲明」。

然而，他警告說，這項研究代表了「第一個數據點，當然，這不是該主題的最終結論。目前仍在進行的其他研究也在將 ECT 與 IV 氯胺酮進行比較，我們期待看到結果」。

麥金太爾說，15% 到 20% 的研究患者患有精神病性抑鬱症這一事實也值得注意。

「我們一直對在這些患者中使用氯胺酮猶豫不決，我認為原因很明顯，但我們最近發表了一篇論文，顯示它對這些患者是安全且非常有效的」，他說。

將氯胺酮作為一種治療選擇很重要，因為大多數可以從 ECT 中受益的患者都會拒絕它，這通常是因為與該程序相關的恥辱感，這通常在電影和其他媒體中被負面描述。

「在我職業生涯的幾乎每一天，我都在推薦 ECT，100 個人中有 98 次說，『謝謝，但不，謝謝』。這是一個問題，因為 ECT 非常有效」。

該研究由瑞典研究委員會、Crafoord 基金會、斯科訥地區委員會、Königska 基金會、Lions forsknings 基金會斯科訥和 OM Perssons 捐贈基金會資助。 Movhed Rad 收到了 Lundbeck 的講師酬金。 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。

Int J Neuropsychopharmacol《國際神經精神藥理學雜誌》。 2021年12月4日線上發布。全文

Ketamine vs ECT for Depression: First Head-to-Head Results

Megan Brooks / January 28, 2022

Intravenous ketamine is effective for treating depression but is inferior to electroconvulsive therapy (ECT), new research suggests.

In the first head-to-head trial, ECT was more effective than IV ketamine in hospitalized patients with severe depression, with higher remission rates and a greater reduction in symptoms.

However, ketamine led to remission in nearly half of participants and is a “valuable” option for treating severe depression, particularly in younger patients, investigators note.

The high rate of remission for ketamine infusion “indicates that it definitely can be used in a clinical setting, but it is more probable that a patient will achieve remission with ECT compared to ketamine,” principal investigator Pouya Movahed Rad, MD, PhD (Pharmacology), senior consultant and researcher in psychiatry, Lund University, Sweden, told Medscape Medical News.

Results of the KetECT study were recently published online in the International Journal of Neuropsychopharmacology.

Primary Focus on Remission

The parallel, open-label, non-inferiority study included 186 patients aged 18-85 years who were hospitalized with severe unipolar depression and had a score of at least 20 on the Montgomery–Åsberg Depression Rating Scale (MADRS).

Participants were randomly allocated (1:1) to thrice-weekly infusions of racemic ketamine (0.5 mg/kg over 40 minutes) or ECT. All patients continued to take their antidepressant medication during the study. The primary outcome was remission, defined as a MADRS score of 10 or less.  

Results showed the remission rate was significantly higher in the ECT group than in the ketamine group (63% vs 46%, respectively; P = .026). The 95% confidence interval of the difference in remission rates was estimated between 2% and 30%. 

Both ketamine and ECT required a median of six treatment sessions to induce remission.

Age was a factor in the findings. In the ECT group, remission was significantly more likely in older patients (age 51-85 years) compared with younger patients (18-50 years), with remission rates of 77% and 50%, respectively.

But the opposite was true in the ketamine group, with significantly higher remission rates in younger vs older patients (61% vs 37%).

The study results also support the safety and efficacy of ketamine in patients with psychotic depression, which was present in 15% of patients in the ECT group and 18% of those in the ketamine group.

In this subgroup, half of patients with psychotic depression remitted after ketamine, with no indications of adverse reactions particular for these patients. The remission rate with ECT was 79%.

During the 12-month follow-up period, rate of relapse among remitters was similar at 64% in the ECT group and 70% in the ketamine group (log rank P = .44).

Let the Patient Decide

As expected, ECT and ketamine had distinct side effect profiles. Prolonged amnesia was more common with ECT and reports of dissociative side effects, anxiety, blurred vision, euphoria, vertigo, and diplopia (double vision) were more common with ketamine. 

“Dissociative symptoms were, as expected, observed during treatment with ketamine, but they were brief and in the majority of cases mild and tolerable,” Movahed Rad said.

The investigators note that participating study sites all had long-time experience with ECT but no experience administering ketamine.

“Staffs, and some patients, were familiar with side effects common to ECT but were less prepared for the adverse psychological effects of ketamine. This, and knowing ECT was available after the study, probably contributed to the higher dropout rate in the ketamine group,” they write.

If both ECT and ketamine are available, “the patient’s preference should, of course, be taken into account when choosing treatment,” said Movahed Rad.

“Ketamine should be offered if ECT is not available, or cannot be given due to excessive risks with anesthesia or other somatic risk factor. Patients who have not responded to ECT or have had unacceptable side effects should be offered ketamine infusion and vice versa,” he added.

A Good Alternative

Commenting on the findings for Medscape Medical News, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Canada, said the data confirm ECT is highly effective for treatment-resistant depression and show that “newcomer” IV ketamine also performs “exceptionally well.”

“This is an extremely important study that really establishes the efficacy of ketamine in a very difficult to treat population,” added McIntyre, who was not involved in the research.

McIntyre added that this “rigorous, well-designed study addresses a critical question” about the comparative efficacy of ECT and IV ketamine. It also makes “quite a strong statement about the efficacy of ketamine in younger people.”

He cautioned, however, that this study represents the “first data point and, of course, is not the final word on the topic. There are other studies currently still ongoing that are also comparing ECT to IV ketamine and we’ll look forward to seeing the results.”

The fact that 15% to 20% of the study patients had psychotic depression is also noteworthy, said McIntyre.

“We’ve been hesitant to use ketamine in these patients, I think for obvious reasons, but we recently published a paper showing that it is safe and very effective in these patients,” he said.

Having ketamine as a treatment option is important because the majority of patients who could benefit from ECT decline it, often because of the stigma associated with the procedure, which is often portrayed negatively in films and other media.

“I have been recommending ECT almost every day of my professional life and 98 times out of 100 people say, ‘Thanks but no thanks.’ That’s a problem because ECT is so effective.

The study was funded by the Swedish Research Council, The Crafoord Foundation, Skåne Regional Council, The Königska Foundation, Lions forsknings foundation Skåne, and the OM Perssons donation foundation. Movhed Rad has received lecturer honoraria from Lundbeck. 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.

Int J Neuropsychopharmacol. Published online December 4, 2021. Full text

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