Distressing voices are a core symptom of psychosis, for which existing treatments are currently suboptimal; as such, new effective treatments for distressing voices are needed. AVATAR therapy involves voice-hearers engaging in a series of facilitated dialogues with a digital embodiment of the distressing voice. This randomized phase 2/3 trial assesses the efficacy of two forms of AVATAR therapy, AVATAR-Brief (AV-BRF) and AVATAR-Extended (AV-EXT), both combined with treatment as usual (TAU) compared to TAU alone, and conducted an intention-to-treat analysis. We recruited 345 participants with psychosis; data were available for 300 participants (86.9%) at 16 weeks and 298 (86.4%) at 28 weeks. The primary outcome was voice-related distress at both time points, while voice severity and voice frequency were key secondary outcomes. Voice-related distress improved, compared with TAU, in both forms at 16 weeks but not at 28 weeks. Distress at 16 weeks was as follows: AV-BRF, effect −1.05 points, 96.5% confidence interval (CI) = −2.110 to 0, P = 0.035, Cohen’s d = 0.38 (CI = 0 to 0.767); AV-EXT −1.60 points, 96.5% CI = −3.133 to −0.058, P = 0.029, Cohen’s d = 0.58 (CI = 0.021 to 1.139). Distress at 28 weeks was: AV-BRF, −0.62 points, 96.5% CI = −1.912 to 0.679, P = 0.316, Cohen’s d = 0.22 (CI = −0.247 to 0.695); AV-EXT −1.06 points, 96.5% CI = −2.700 to 0.586, P = 0.175, Cohen’s d = 0.38 (CI = −0.213 to 0.981). Voice severity improved in both forms, compared with TAU, at 16 weeks but not at 28 weeks whereas frequency was reduced in AV-EXT but not in AV-BRF at both time points. There were no related serious adverse events. These findings provide partial support for our primary hypotheses. AV-EXT met our threshold for a clinically significant change, suggesting that future work should be primarily guided by this protocol. ISRCTN registration: ISRCTN55682735.

令人痛苦的声音是精神病的核心症状，目前的治疗方法并不理想;因此，需要新的有效治疗方法来治疗令人痛苦的声音。AVATAR 疗法涉及听声者与令人痛苦的声音的数字化身进行一系列促进对话。这项随机 2/3 期试验评估了两种形式的 AVATAR 疗法的疗效，即 AVATAR-Brief （AV-BRF） 和 AVATAR-Extended （AV-EXT），两者均联合常规治疗 （TAU） 与单独使用 TAU 相比，并进行了意向性治疗分析。我们招募了 345 名患有精神病的参与者;300 名参与者 （86.9%） 在 16 周时和 298 名 （86.4%） 在 28 周时的数据可用。主要结局是两个时间点的语音相关痛苦，而语音严重程度和语音频率是关键的次要结局。与 TAU 相比，两种形式的语音相关痛苦在 16 周时都有所改善，但在 28 周时没有改善。16 周时的痛苦如下：AV-BRF，效应 -1.05 分，96.5% 置信区间 （CI） = -2.110 至 0，P = 0.035，Cohen 的 d = 0.38 （CI = 0 至 0.767）;AV-EXT -1.60 分，96.5% CI = -3.133 至 -0.058，P = 0.029，Cohen 的 d = 0.58（CI = 0.021 至 1.139）。28 周时的痛苦为：AV-BRF，-0.62 分，96.5% CI = -1.912 至 0.679，P = 0.316，Cohen d = 0.22（CI = -0.247 至 0.695）; AV-EXT -1.06 分，96.5% CI = -2.700 至 0.586，P = 0.175，Cohen 的 d = 0.38（CI = -0.213 至 0.981）。与 TAU 相比，两种形式的嗓音严重程度在 16 周时都有所改善，但在 28 周时没有改善，而 AV-EXT 的频率在两个时间点都降低，而 AV-BRF 的频率没有降低。没有相关的严重不良事件。这些发现为我们的主要假设提供了部分支持。 AV-EXT 达到了我们临床显着变化的阈值，表明未来的工作应主要以该方案为指导。ISRCTN 注册：ISRCTN55682735。