探討Ketamine與Sertraline、Paroxetine用於治療創傷後壓力症候群（PTSD）的療效：系統性文獻回顧、網絡統合分析與臨床試驗計畫書

Abstract

背景： 創傷後壓力症候群（PTSD）是由心理創傷對身體、認知、情感以及行為引起的影響，並對病人的社會、職業和人際關係功能造成了顯著障礙。迄今為止，僅有Sertraline和Paroxetine兩種藥物在二十年前被FDA批准用於治療PTSD，但效果有限。近期越來越多的證據支持Ketamine對PTSD展示出迅速且持久的療效。然而，尚無研究比較Ketamine與Sertraline和Paroxetine間的療效。本研究旨在透過系統性文獻回顧和網絡統合分析來探討Ketamine、Sertraline和Paroxetine之間的療效。

方法： 本研究透過 Cochrane Central Register of Controlled Trials、Embase 和 PubMed 資料庫搜尋Ketamine、Sertraline和Paroxetine治療PTSD的使用情況。符合納入條件的研究會被用於數據分析，包括 PTSD 症狀分數變化和治療反應率。透過統合分析與網絡統合分析，以評估不同治療組的療效。結果的報告包含標準化平均分數和勝算比，及其相應的95%信賴區間。本研究亦透過次族群分析以進一步探討在不同族群中之療效。

結果： 共有22篇研究被納入分析。研究顯示，Ketamine、Sertraline和Paroxetine相比安慰劑均顯著降低了PTSD症狀分數。通過網絡統合分析比較Ketamine與Sertraline和Paroxetine的療效時，差異並未達到統計學意義（症狀分數平均變化- Sertraline對Ketamine：SMD= 0.09，[95% CI –0.59 到 0.76]；Paroxetine對Ketamine：SMD= 0.37，[95% CI -0.28 到 0.88]；反應率- Sertraline對Ketamine：OR= 0.59，[95% CI 0.23 到 1.53]；Paroxetine對Ketamine：OR= 0.82，[95% CI 0.30 到2.24]）。在多數的次族群分析中，Ketamine 相比Sertraline 和Paroxetine 具有更明顯的效果，然而結果也未達到統計學意義。

結論： Ketamine 在改善PTSD 症狀方面與Sertraline 和Paroxetine 療效相當。未來尚待進行更多的臨床試驗，探討Ketamine 與SSRIs 或其組合的療效。此類研究有望完善治療方案，進一部提升PTSD 的治療成果。

Background Posttraumatic stress disorder (PTSD) is characterized as "the complex somatic, cognitive, affective, and behavioral effects of psychological trauma, which leads to considerable social, occupational, and interpersonal dysfunction. To date, only two drugs, paroxetine, and sertraline were approved by the FDA for the therapy of PTSD two decades ago, however, with limited efficacy. Recently accumulating evidence supports that ketamine exhibits a rapid and persistent effect against PTSD. Nevertheless, there has been no study comparing the efficacy between the approved medication (paroxetine, and sertraline) and ketamine. This study aims to investigate the efficacy between ketamine, paroxetine and sertraline through system review and network meta-analysis.

Methods Cochrane Central Register of Controlled Trials, Embase, PubMed were searched to examine the use of ketamine, sertraline, paroxetine for the treatment of PTSD. Studies were included if they met the predefined criteria. Data used for analysis comprised change of PTSD symptom scores and response rates. Meta-analysis and network meta-analysis were performed to assess the effect sizes across treatment groups. Standardized mean differences and odds ratios, along with their respective 95% confidence intervals, were calculated to evaluate the effects on outcomes across the three treatment groups. Subgroup analyses were conducted to examine the influence of trial features.

Results A total of 22 studies were ultimately included in this systematic review and meta-analysis. The analysis revealed that ketamine, sertraline, and paroxetine all significantly reduced PTSD symptom scores compared to placebo. When comparing the efficacy of ketamine with sertraline and paroxetine via network meta-analysis, the differences were not statistically significant (mean change- sertraline vs ketamine: SMD= 0.09, [95% CI –0.59 to 0.76]; paroxetine vs ketamine: SMD= 0.30, [95% CI -0.28 to 0.88] ; response rate- (sertraline versus ketamine: OR= 0.59, [95% CI 0.23 to 1.53]; paroxetine versus ketamine: OR= 0.82, [95% CI 0.30 to 2.24]). In most of the subgroup analysis, ketamine had a more pronounced effect compared to sertraline and paroxetine, although this observation did not achieve statistical significance as well.

Conclusions This systematic review and meta-analysis demonstrate that ketamine is as effective as sertraline and paroxetine in improving PTSD symptoms. Future randomized clinical trials exploring the efficacy of ketamine versus SSRIs or their combination, will be essential to clarify the comparative effectiveness of these treatments. Such research could refine treatment protocols and foster more personalized therapeutic approaches for managing PTSD, potentially enhancing outcomes for patients suffering from this condition.