Explore the vast range of titles available.

The serotonin-receptor modulator pimavanserin reduces psychosis in patients with Parkinson’s disease. In a randomized discontinuation trial involving patients with psychosis related to several types of dementia, the frequency of relapse over a period of 26 weeks was 13% with pimavanserin and 28% with placebo.

Auditory hallucinations (AHs) are debilitating and often treatment‐resistant symptoms of schizophrenia (SZ). Real‐time functional magnetic resonance imaging (fMRI) neurofeedback (NFB) is emerging as a flexible brain circuit‐based tool for targeting AH via self‐modulation of brain activity. A better understanding of what baseline characteristics predict NFB success will enhance its clinical utility. Previous work suggests that AH symptomology implicates measures across multiple modalities, including T1 structural MRI (sMRI), diffusion‐weighted MRI (dMRI), and resting‐state fMRI (rsfMRI). Specifically, AH severity and treatment response are associated with thinner superior temporal gyrus (STG), thinner dorsolateral prefrontal cortex (DLPFC), reduced white matter integrity in tracts connecting brain regions implicated in SZ symptomatology, increased within‐default mode network (DMN) connectivity, and reduced DMN–DLPFC anticorrelation. In this study, we tested the individual and combined contributions of multimodal brain features for the prediction of AH change after NFB in adults ( N  = 25, 36.1 ± 10.0 years, 24% females) with SZ spectrum disorders (SZ or schizoaffective disorder) and frequent medication‐resistant AH. Participants underwent a baseline MRI scan (including sMRI, dMRI, and rsfMRI) and were randomly assigned to receive NFB from their STG ( n  = 12, real condition) or NFB from their motor cortex (MC) ( n  = 13, sham condition). NFB success was operationalized as the improvement in AH severity after NFB. We found that higher baseline AH severity, greater STG thickness, decreased dorsal cingulum integrity, increased within‐DMN resting‐state functional connectivity, and increased DMN–DLPFC anticorrelation were each individually correlated with reduction in AH severity. However, in a combined regression model, DMN–DLPFC connectivity emerged as the only independent variable that explained the unique variance in AH change. These results suggest that a specific rsfMRI measure, namely DMN–DLPFC connectivity, may be a promising predictor of NFB success in reducing AH and support the precision medicine approach. Trial Registration: ClinicalTrials.gov identifier: NCT03504579

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 . A randomized controlled trial involving people with psychosis who hear distressing voices reported that two different forms of AVATAR therapy, an intervention where voice-hearers engage with a digital avatar representing this distressing voice, reported further improvements in voice-related distress at 16 weeks but not at 28 weeks on top of standard of care.

Background Hearing voices (“auditory hallucinations”) is associated with numerous negative outcomes, including hospitalisation, suicidality, and impaired functioning. Currently, the main treatment approaches are antipsychotic medication and cognitive behavioural therapy (CBT), yet both have variable effectiveness and are often unavailable to those without a schizophrenia diagnosis. Furthermore, CBT does not consistently address the role of trauma in voice onset and maintenance. In response to these unmet needs, a feasibility/acceptability trial of a new intervention, Talking With Voices (TWV), was conducted. TWV involves a therapist speaking to the voice(s) while the client repeats its response verbatim, with the aim of promoting recovery and reducing voice-related distress. This prior pilot study ( N  = 50) found excellent feasibility/acceptability data amongst participants with schizophrenia, and signals of positive change in measures of personal recovery and voice relating. The next step is to evaluate treatment mechanisms and clinical efficacy of TWV in a transdiagnostic population. Methods We aim to establish TWV’s clinical efficacy in a multisite RCT for adults with serious mental health problems (SMHP) who hear persistent, distressing voices, and to assess whether improved measures of personal recovery and negative voice impact are mediated via key psychological mechanisms (improved relating to, and beliefs about, voices; and reductions in dissociation and negative self-beliefs). We aim to recruit 296 participants from psychiatric services across 4 UK sites (Manchester, London, Newcastle, and Oxford) who will be randomised to either treatment (TWV + treatment as usual [TAU]) or control (TAU only). The primary outcome is total score on the Questionnaire About the Process of Recovery. Secondary outcomes include overall voice severity and other relevant dimensions of voices and trauma sequalae, with mediational and outcome variables collected at baseline, 8 months (post-treatment), and 14 months. Discussion The study will investigate the clinical efficacy of a novel intervention deliverable within healthcare services, including hypothesised mechanisms of change to identify key psychological targets for ameliorating distressing voices in a transdiagnostic population. Potential benefits include improving the effectiveness and accessibility of evidence-based psychosocial interventions for SMHP. Trial registration ISRCTN, ISRCTN15897915. Registered 13 July 2023.

One in four patients with schizophrenia responds poorly to antipsychotic medication, continuing to hear persecutory auditory hallucinations. Patients who are able to sustain a dialogue with their persecutor feel much more in control. To develop a computerised system that enables the patient to create an avatar of their persecutor. To encourage them to engage in a dialogue with the avatar, which the therapist is able to control so that the avatar progressively yields control to the patient. Avatar therapy was evaluated by a randomised, single blind, partial crossover trial comparing the novel therapy with treatment as usual (TAU). We used three main outcome measures: (a) the Psychotic Symptom Rating Scale (PSYRATS), hallucinations section; (b) the Omnipotence and Malevolence subscales of the Revised Beliefs About Voices Questionnaire (BAVQ-R); and (c) the Calgary Depression Scale (CDS). The control group showed no change over time in their scores on the three assessments, whereas the novel therapy group showed mean reductions in the total PSYRATS score (auditory hallucinations) of 8.75 (P = 0.003) and in the BAVQ-R combined score of omnipotence and malevolence of the voices of 5.88 (P = 0.004). There was no significant reduction in the CDS total score for depression. For the crossover control group, comparison of the period of TAU with the period of avatar therapy confirmed the findings of the previous analysis. The effect size of the therapy was 0.8. Avatar therapy represents a promising treatment for medication-resistant auditory hallucinations. Replication with a larger sample is required before roll-out to clinical settings.

Abstract Background and Hypothesis Intrusive mental images and negative schematic beliefs have been identified as maintenance and possible causal factors for some psychotic experiences, with limited focus in existing therapies in psychosis. Our primary aim was to assess the feasibility and acceptability of undertaking a randomized controlled trial (RCT) of a novel, imagery focused psychological therapy for psychosis (iMAPS). Study Design An assessor-blind RCT (iMAPS-2). Participants who were help seeking; with hallucinations or delusions, who reported distressing intrusive mental imagery were eligible to take part. Participants were randomly assigned (2:1) to receive 12 sessions of iMAPS therapy plus standard care or treatment as usual (TAU). Assessments were undertaken at 0, 16 and 28 weeks. The primary feasibility outcomes were recruitment target, retention at 16 week follow up and number of therapy sessions attended. Study Results The trial recruitment was 100% of target (45 participants). The study had a high rate of retention of 80% (36 participants) at 16-week primary endpoint, a high rate of adherence to the imagery focused therapy (77%) and positive qualitative feedback. There were two serious adverse events in the iMAPS therapy arm deemed unrelated to treatment and zero in the TAU group. Conclusions This is the largest trial to date of imagery focused therapy for psychosis, demonstrating it is safe. An adequately powered clinical and cost effectiveness trial is warranted to provide an estimate of the effects of the iMAPS therapy. Trial Registration ISRCTN 81150786.

Transcranial direct current stimulation (tDCS) has been proposed as a therapeutic option for treatment-resistant auditory verbal hallucinations (AVH) in schizophrenia. In such cases, repeated sessions of tDCS are delivered with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. Despite promising findings, the clinical response to tDCS is highly heterogeneous among patients. Here, we explored baseline differences between responders and nonresponders to frontotemporal tDCS using electric field modeling. We hypothesized that responders would display different tDCS-induced electric field strength in the brain areas involved in AVH compared to nonresponders.Using baseline structural MRI scans of 17 patients with schizophrenia and daily AVH who received 10 sessions of active frontotemporal tDCS, we constructed individual realistic whole brain models estimating electric field strength. Electric field maps were compared between responders (n = 6) and nonresponders to tDCS (n = 11) using an independent two-sample t test. Clinical response was defined as at least a 50% decrease of AVH 1 month after the last tDCS session.Results from the electric field map comparison showed that responders to tDCS displayed higher electric field strength in the left transverse temporal gyrus at baseline compared to nonresponders (T = 2.37; p = 0.016; 32 voxels).These preliminary findings suggested that the strength of the tDCS-induced electric field reaching the left transverse temporal gyrus could play an important role in the response to frontotemporal tDCS. In addition, this work suggests the interest of using electric field modeling to individualize tDCS and increase response rate.