Digital AVATAR therapy for distressing voices in psychosis: the phase 2/3 AVATAR2 trial.

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 .