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

TY - JOUR

T1 - Digital AVATAR therapy for distressing voices in psychosis

T2 - the phase 2/3 AVATAR2 trial

AU - Garety, Philippa A

AU - Edwards, Clementine J

AU - Jafari, Hassan

AU - Emsley, Richard

AU - Huckvale, Mark

AU - Rus-Calafell, Mar

AU - Fornells-Ambrojo, Miriam

AU - Gumley, Andrew

AU - Haddock, Gillian

AU - Bucci, Sandra

AU - McLeod, Hamish J

AU - McDonnell, Jeffrey

AU - Clancy, Moya

AU - Fitzsimmons, Michael

AU - Ball, Hannah

AU - Montague, Alice

AU - Xanidis, Nikos

AU - Hardy, Amy

AU - Craig, Thomas K J

AU - Ward, Thomas

N1 - Publisher Copyright: © The Author(s) 2024.

PY - 2024/12/1

Y1 - 2024/12/1

N2 - 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.

AB - 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.

KW - Humans

KW - Psychotic Disorders/therapy

KW - Male

KW - Female

KW - Adult

KW - Hallucinations/therapy

KW - Middle Aged

KW - Treatment Outcome

KW - Young Adult

KW - Voice

KW - Avatar

UR - http://www.scopus.com/inward/record.url?scp=85207473536&partnerID=8YFLogxK

U2 - 10.1038/s41591-024-03252-8

DO - 10.1038/s41591-024-03252-8

M3 - Article

C2 - 39468363

SN - 1078-8956

VL - 30

SP - 3658

EP - 3668

JO - Nature Medicine

JF - Nature Medicine

IS - 12

M1 - 366

ER -