An ‘Unusual Finding’
The study’s primary outcome was voice-related distress at 16 and 28 weeks. Although the TAU plus AVATAR-Extended group did show a significant decrease in distress at 16 weeks vs TAU alone (–1.6 points; P = .029), the improvement was no longer significant at the 28-week follow-up (P = .175). The same was also true for the key secondary outcome of reduction in voice severity (–2.32 points; P = .009 at 16 weeks but P =.1 at 28 weeks).
The investigators noted that this might be caused by the number of dropouts in the AVATAR-Extended group by the 28-week timepoint. The completion rate for those patients was only 58%. The completion rate for the shorter, AVATAR-Brief group was 82%.
On the other hand, the other key secondary outcome of voice frequency was significantly reduced with AVATAR-Extended at both 16 weeks (–0.62 point; P = .01) and 28 weeks (–0.89 point; P = .003).
“This is an unusual finding. We’re not aware of any other psychological therapy that shows a reduction in the occurrence of the voice,” Garety said.
For TAU plus AVATAR-Brief, there were improvements at 16 weeks for distress (-1.05 points; P = .035) vs TAU alone. However, the researchers noted that this version of the therapy was just below the prespecified threshold for a clinically significant change and was at the threshold for statistical significance.
Although the shorter therapy was associated with a reduction in voice severity level at 16 weeks (–2.04 points; P = .017) vs TAU alone, there was no reduction in distress or voice severity at 28 weeks. There was no improvement in voice frequency at either timepoint.
Both the brief and the extended versions of AVATAR therapy showed improved mood and anxiety levels at 16 weeks and sustained improvement in well-being and recovery, the researchers noted.
“The short version, as expected, did deliver benefits posttreatment, but clearly the extended, optimized version outperformed the brief version. It had stronger and more lasting effects across quite a wide range of outcomes that matter to people who hear voices,” Garety said.
“In the extended version, people felt more empowered. And in just that version, the frequency of voices was reduced, which is a very important outcome,” she added.
Safety Issues?
There were 58 serious adverse events (SAEs) in total, with 51% of those occurring in the AVATAR-Extended group. Two participants in that group died; however, independent reviews deemed these events as not related to the intervention.
In addition, there were no “definitely related” SAEs and only a small number of “possibly related” SAEs, which typically included hospitalization with other contributory factors.
Garety noted during a press briefing that AVATAR therapy has now been demonstrated to be safe across two large trials.
Study limitations cited included no direct comparison between AVATAR-Brief and AVATAR-Extended or between AVATAR therapy and a different type of psychological treatment.
Overall, “we recommend that future development and provision of AVATAR therapy is primarily guided” by the AVATAR-Extended protocol, the investigators wrote.
Because the therapy was recommended by a National Institute for Health and Care Excellence Early Value Assessment, the investigators are now seeking to provide it in routine National Health Service settings to gather further real-world evidence of effectiveness over the next 3 years.