氯胺酮快速，有效應對自殺危機

資料來源：梅根.布魯克斯 / 2022 年 2 月 10 日 / Medscape 醫學新聞 / 財團法人台灣紅絲帶基金會編譯

一項大型隨機對照試驗的結果顯示，氯胺酮是一種快速有效的自殺意念治療方法，基於初級心理健康診斷具有「重大」調節作用。

此外，在雙相情感障礙患者中觀察到氯胺酮的強烈作用，「而這種作用是中等的，在患有其他精神疾病的患者中並沒有達到顯著性，並且出乎意料地在患有重度抑鬱症的患者中不顯著」，研究人員寫。

「我們在同一項研究中首次評估了氯胺酮對三組先驗定義的非精神病患者的影響：雙相情感障礙患者、抑鬱症患者和其他診斷患者」，研究人員 Fabrice Jollant，法國巴黎大學精神病學教授、醫學博士告訴 Medscape 醫學新聞。

「這讓我們發現，共病是氯胺酮臨床效果的重要調節劑，氯胺酮的作用在雙相情感障礙患者中尤為顯著」，Jollant 補充道。

該研究於 2 月 2 日於線上發表在 BMJ《英國醫學雜誌》 上。

迅速，完全緩解

該研究包括 156 名自願入住 7 家法國教學醫院的有嚴重自殺意念的成年人，其中 52 人患有雙相情感障礙，56 人患有抑鬱症，48 人患有其他精神疾病。

除了常規治療外，他們被隨機分配到基準線和 24 小時內進行兩次靜脈輸注氯胺酮（0.5 mg/kg）或安慰劑（鹽水），每次 40 分鐘。

主要結果是患者在第 3 天完全緩解自殺的比率，根據 19 個 0 到 2 分的項目（最高分 38），臨床醫生評定的自殺意念量表評分為 3 分或更低。

「我們調查了自殺念頭的完全緩解，而不僅僅是反應，這通常被定義為在給定量表上降低 50% 的分數。如果人們仍然有輕微的自殺傾向，那麼自殺風險仍然存在。我們希望所有的自殺念頭都消失」喬蘭特說。

他們發現，在輸注兩次氯胺酮後的第 3 天，與輸注安慰劑相比，更多的患者在第 3 天達到自殺意念的完全緩解（63% 對 32%；優勢比 [OR]，3.7；95% CI，1.9 – 7.3；P < .001） .

作者報告說，氯胺酮的這種抗自殺作用很快，在第一次輸注後僅 2 小時就有 44% 的緩解。

氯胺酮對雙相情感障礙患者自殺緩解的影響最大，85% 在第 3 天達到完全緩解（OR，14.1；95% CI，3.0 – 92.2；P < .001），而在雙相情感障礙患者中，這一比例為 42%。抑鬱症 (OR, 1.3; 95% CI, 0.3 – 5.2; P = .6) 或 62% 患有其他疾病的人 (OR, 3.7; 95% CI, 0.9 – 17.3; P = .07)。

治療後 6 週，氯胺酮組的緩解率仍然很高，儘管與安慰劑組相比無顯著性差異（69.5% 對 56.3%；OR，0.8；95% CI，0.3 – 2.5；P = .7）。

研究人員指出，氯胺酮對自殺意念的有益影響可能是透過對心理痛苦的影響來介導的。

「雖然精神上的痛苦並不一定會導致自殺念頭，但最近的研究顯示，有嚴重自殺念頭的人（尤其是那些有計畫的人）也有高度的精神痛苦。因此氯胺酮可能通過減輕精神痛苦的鎮痛機制發揮作」，他們寫道。

氯胺酮的副作用是「有限的」，沒有出現躁狂或精神病症狀。主要副作用，包括鎮靜、去國家化/去現實化、噁心和頭暈，持續時間很短，發生在約 10% 或更少的患者中。

研究人員承認，氯胺酮對本研究中的重度抑鬱症患者的不顯著影響「難以解釋」。

他們指出，這項研究可能缺乏檢測這些患者的影響的能力。此外，這一組可能特別異質，更多的患者對安慰劑效應敏感，更多的患者需要重複輸注氯胺酮。

氯胺酮的新視角

英國牛津大學精神病學系 Wellcome Trust 博士培訓研究員 Riccardo De Giorgi 在隨附的社論中表示，這項研究挑戰了目前對氯胺酮的看法。

De Giorgi 寫道，抑鬱組的「意外」結果（無益處）「可能違背了重度抑鬱症患者將從氯胺酮中獲益最多的普遍觀念」。

「事實上，在抑鬱症患者中，常規照護和氯胺酮均導致自殺意念的降低、可比較緩解率分別為 35.7% 和 42.3%」，De Giorgi 指出。

「雖然這項研究因此證實，許多患有抑鬱症和自殺意念的患者仍然無法接受現有的治療，但它顯示另一組重要的急性自殺意念患者，即雙相情感障礙患者，可以從氯胺酮中受益」，De Giorgi 寫道。

「再一次，有證據顯示，在考慮使用氯胺酮之前必須進行仔細的臨床評估，這必須保留用於特定的臨床表現，而不是不分青紅皂白地給予任何有自殺念頭的人」，他總結道。

該研究的資金由 Program Hospitalier de Recherche Clinique National 提供。 Jollant 和 De Giorgi 沒有披露任何相關的財務關係。

BMJ《英國醫學雜誌》。 2022 年 2 月 2 日於線上發布。全文，社論

Ketamine Fast, Effective for Suicidal Crises

Megan Brooks / February 10, 2022

Ketamine is a rapid and effective treatment for suicidal ideation and has a “major” moderating effect based on the primary mental health diagnosis, results of a large randomized controlled trial shows.

In addition, a strong effect of ketamine was observed in patients with bipolar disorder, “whereas the effect was moderate and did not quite reach significance in those with other psychiatric disorders and unexpectedly was non-significant in those with major depressive disorders,” the researchers write.

“We assessed for the first time in the same study the effect of ketamine on three a-priori defined groups of nonpsychotic patients: those with a bipolar disorder, those with a depressive disorder, and those with other diagnoses,” study investigator Fabrice Jollant, MD, PhD, professor of psychiatry, University of Paris, France, told Medscape Medical News.

“This allowed us to find that comorbid disorders are important modulators of the clinical effects of ketamine, and that the effect of ketamine is particularly marked among patients with a bipolar disorder,” Jollant added.  

The study was published online February 2 in The BMJ.

Swift, Full Remission

The study included 156 adults admitted voluntarily to seven French teaching hospitals with severe suicidal ideation, including 52 with bipolar disorder, 56 with depressive disorder, and 48 with other psychiatric diagnoses.

They were randomly allocated to two 40-minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) administered at baseline and 24 hours, in addition to usual treatment. 

The primary outcome was the rate of patients in full suicidal remission at day 3, confirmed by a score of 3 or less on a clinician-rated scale for suicidal ideation based on 19 items scored 0 to 2 (maximum score, 38).

“We investigated the full remission of suicidal ideas and not only the response, which is usually defined as a reduction of 50% of scores on a given scale. If people remain slightly suicidal, the suicidal risk persists. We want all suicidal ideas to disappear,” said Jollant.

They found that more patients reached full remission of suicidal ideas at day 3 after two ketamine infusions than after placebo infusions (63% vs 32%; odds ratio [OR], 3.7; 95% CI, 1.9 – 7.3; P < .001).

This anti-suicidal effect of ketamine was rapid, with 44% remission only 2 hours after the first infusion, the authors report.

The effect of ketamine on suicidal remission was greatest in patients with bipolar disorder, with 85% achieving full remission at day 3 (OR, 14.1; 95% CI, 3.0 – 92.2; P < .001), compared with 42% of patients with depressive disorder (OR, 1.3; 95% CI, 0.3 – 5.2;  P = .6) or 62% of those with other disorders (OR, 3.7; 95% CI, 0.9 – 17.3; P = .07).

At 6 weeks after treatment, remission in the ketamine group remained high, although nonsignificantly vs placebo (69.5% vs 56.3%; OR, 0.8; 95% CI, 0.3 – 2.5; P = .7).

The researchers note the beneficial effect of ketamine on suicidal ideation could be mediated by an effect on psychological pain.

“Although mental pain does not necessarily lead to suicidal ideas, recent studies suggest that individuals with severe suicidal ideas (notably those with a plan) also have high levels of mental pain. Ketamine might therefore exert its effects through analgesic mechanisms that reduce mental pain,” they write.

Ketamine’s side effects were “limited” with no manic or psychotic symptoms seen. The main side effects, including sedation, denationalization/derealization, nausea, and dizziness, were of short duration and occurred in about 10% or fewer patients.

The investigators acknowledge that the nonsignificant effect of ketamine in the patients with major depressive disorders in this study is “challenging to interpret.”

They point out the study may have lacked power to detect an effect in these patients. In addition, this group might be particularly heterogeneous, with more patients sensitive to a placebo effect and more patients requiring repeated ketamine infusions.

A New Perspective on Ketamine

In an accompanying editorial, Riccardo De Giorgi, Wellcome Trust doctoral training fellow, Department of Psychiatry, University of Oxford, United Kingdom, said the study challenges current thinking about ketamine.

The “unexpected” outcome (no benefit) in the depressive group “perhaps defies the prevailing notion that patients with major depression would benefit most from ketamine,” De Giorgi writes.

“In fact, both usual care and ketamine given with usual care led to low, comparable remission rates of 35.7% and 42.3% for suicidal ideation, respectively, in patients with depressive disorder,” De Giorgi points out.

“While this study therefore confirms that many patients with depressive disorder and suicidal ideation remain poorly served by available treatments, it shows that another important group of patients with acute suicidal ideation, those with bipolar disorder, could benefit from ketamine,” De Giorgi writes.

“Once again, here is evidence that careful clinical evaluation must precede any consideration of ketamine use, which must be reserved for specific clinical presentations and not given indiscriminately to anyone presenting with suicidal thoughts,” he concludes.

Funding for the study was provided by Programme Hospitalier de Recherche Clinique National. Jollant and De Giorgi have disclosed no relevant financial relationships.

BMJ. Published online February 2, 2022. Full text, Editorial