Wasserthal Sven, Muthesius Ana, Hurlemann René, Ruhrmann Stephan, Schmidt Stefanie J, Hellmich Martin, Schultze-Lutter Frauke, Klosterkötter Joachim, Müller Hendrik, Meyer-Lindenberg Andreas, Poeppl Timm B, Walter Henrik, Hirjak Dusan, Koutsouleris Nikolaos, Fallgatter Andreas J, Bechdolf Andreas, Brockhaus-Dumke Anke, Mulert Christoph, Philipsen Alexandra, Kambeitz Joseph
Division of Medical Psychology, Department of Psychiatry and Psychotherapy, University Hospital of Bonn, Bonn, Germany.
Department of Psychiatry and Psychotherapy, University of Cologne and University Hospital Cologne, Cologne, Germany.
Schizophr Bull Open. 2024 Feb 28;5(1):sgae005. doi: 10.1093/schizbullopen/sgae005. eCollection 2024 Jan.
Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of -acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients.
In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months.
While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups.
The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.
临床精神病高危状态（CHR-P）为早期干预提供了契机，近期试验表明，使用N-乙酰半胱氨酸（NAC）治疗精神分裂症取得了令人鼓舞的结果。此外，综合预防性心理干预（IPPI）通过社会认知矫正来帮助预防CHR-P患者发展为精神病。
在这项双盲、随机、对照多中心试验中，采用2×2析因设计，以研究NAC与安慰剂（PLC）相比以及IPPI与心理应激管理（PSM）相比的效果。主要终点是18个月后发展为精神病或CHR-P症状恶化。
尽管入组不足导致试验提前终止，但共有48名参与者纳入本研究。与接受PLC的患者（IPPI + PLC：56.1±15.3%，PSM + PLC：39.0±17.4%）相比，接受NAC的患者在无事件生存概率估计值上在数值上更高（IPPI + NAC：72.7±13.4%，PSM + NAC：72.7±13.4%）。然而，Kaplan-Meier分析中的对数秩卡方检验显示，NAC与对照组相比（点风险比：0.879，95%CI 0.281 - 2.756）或IPPI与对照组相比（点风险比：0.827，95%CI 0.295 - 2.314），生存概率无显著差异。四组之间不良事件（AE）的数量无显著差异。
在本试验中，无法通过统计学验证NAC或IPPI在预防CHR-P患者精神病方面相对于对照组的优越性。然而，结果显示出一种一致的模式，这使得有必要在未来具有足够统计效力的试验中，进一步将NAC作为一种有前景且耐受性良好的干预措施对CHR患者进行测试。
