Prevalence and nature of multi-sensory and multi-modal hallucinations in people with first episode psychosis

Hallucinations can occur in single or multiple sensory modalities. This study explored how common these experiences were in people with first episode of psychosis (n = 82). Particular attention was paid to the number of modalities reported and whether the experiences were seen to be linked temporally and thematically. It was predicted that those people reporting a greater number of hallucinations would report more delusional ideation, greater levels of distress generally and lower functioning. All participants reported hallucinations in the auditory domain, given the nature of the recruitment. The participants also reported a range of other unusual sensory experiences, with visual and tactile hallucinations being reported by over half. Moreover, single sensory experiences or unimodal hallucinations were less common than two or more hallucination modalities which was reported by 78% of the participants. The number of hallucinations was significantly associated with greater delusional ideation and higher levels of general distress, but not with reduced functioning. It is clear there is a need to refine psychological treatments so that they are better matched to the actual experiences reported by people with psychosis. Theoretical implications are also considered

Managing unusual sensory experiences: A feasibility trial in an At Risk Mental States for psychosis group

Objectives To conduct a feasibility study on a new, tablet-delivered treatment for unusual sensory experiences in service-users with an At Risk Mental States for psychosis. Design A mixed method design was employed, using content analysis to investigate whether service-users and therapists found the new treatment acceptable and helpful. We also collected data on the impact of treatment, but without a control group could not make any claims about effectiveness. Methods Eligible participants were contacted before starting treatment and offered the chance to participate. Assessments were conducted before and after the treatment, which typically was completed in 4–6 sessions by an accredited CBT therapist. A structured interview was used to collect qualitative feedback. Results Qualitative feedback suggested that the treatment was acceptable to service-users and therapists, and the progression criteria were met for recruitment, retention, and adherence to treatment. Conclusions The new treatment targeting subtypes of auditory and visual hallucinations was acceptable to service-users and the benefits of addressing psychological mechanisms thought to contribute to hallucinations was supported by qualitative feedback

Effects of a novel, brief psychological therapy (Managing Unusual Sensory Experiences) for hallucinations in first episode psychosis (MUSE FEP): findings from an exploratory randomised controlled trial.

Hallucinations are a common feature of psychosis, yet access to effective psychological treatment is limited. The Managing Unusual Sensory Experiences for First-Episode-Psychosis (MUSE-FEP) trial aimed to establish the feasibility and acceptability of a brief, hallucination-specific, digitally provided treatment, delivered by a non-specialist workforce for people with psychosis. MUSE uses psychoeducation about the causal mechanisms of hallucinations and tailored interventions to help a person understand and manage their experiences. We undertook a two-site, single-blind (rater) Randomised Controlled Trial and recruited 82 participants who were allocated 1:1 to MUSE and treatment as usual (TAU) (n=40) or TAU alone (n=42). Participants completed assessments before and after treatment (2 months), and at follow up (3-4 months). Information on recruitment rates, adherence, and completion of outcome assessments was collected. Analyses focussed on feasibility outcomes and initial estimates of intervention effects to inform a future trial. The trial is registered with the ISRCTN registry 16793301. Criteria for the feasibility of trial methodology and intervention delivery were met. The trial exceeded the recruitment target, had high retention rates (87.8%) at end of treatment, and at follow up (86.6%), with good acceptability of treatment. There were 3 serious adverse events in the therapy group, and 5 in the TAU group. Improvements were evident in both groups at the end of treatment and follow up, with a particular benefit in perceived recovery in the MUSE group. We showed it was feasible to increase access to psychological intervention but a definitive trial requires further changes to the trial design or treatment

Phase 1-2a multicenter dose-escalation study of ezatiostat hydrochloride liposomes for injection (Telintra®, TLK199), a novel glutathione analog prodrug in patients with myelodysplastic syndrome

<p>Abstract</p> <p>Background</p> <p>Ezatiostat hydrochloride liposomes for injection, a glutathione S-transferase P1-1 inhibitor, was evaluated in myelodysplastic syndrome (MDS). The objectives were to determine the safety, pharmacokinetics, and hematologic improvement (HI) rate. Phase 1-2a testing of ezatiostat for the treatment of MDS was conducted in a multidose-escalation, multicenter study. Phase 1 patients received ezatiostat at 5 dose levels (50, 100, 200, 400 and 600 mg/m²) intravenously (IV) on days 1 to 5 of a 14-day cycle until MDS progression or unacceptable toxicity. In phase 2, ezatiostat was administered on 2 dose schedules: 600 mg/m²IV on days 1 to 5 or days 1 to 3 of a 21-day treatment cycle.</p> <p>Results</p> <p>54 patients with histologically confirmed MDS were enrolled. The most common adverse events were grade 1 or 2, respectively, chills (11%, 9%), back pain (15%, 2%), flushing (19%, 0%), nausea (15%, 0%), bone pain (6%, 6%), fatigue (0%, 13%), extremity pain (7%, 4%), dyspnea (9%, 4%), and diarrhea (7%, 4%) related to acute infusional hypersensitivity reactions. The concentration of the primary active metabolites increased proportionate to ezatiostat dosage. Trilineage responses were observed in 4 of 16 patients (25%) with trilineage cytopenia. Hematologic Improvement-Erythroid (HI-E) was observed in 9 of 38 patients (24%), HI-Neutrophil in 11 of 26 patients (42%) and HI-Platelet in 12 of 24 patients (50%). These responses were accompanied by improvement in clinical symptoms and reductions in transfusion requirements. Improvement in bone marrow maturation and cellularity was also observed.</p> <p>Conclusion</p> <p>Phase 2 studies of ezatiostat hydrochloride liposomes for injection in MDS are supported by the tolerability and HI responses observed. An oral formulation of ezatiostat hydrochloride tablets is also in phase 2 clinical development.</p> <p>Trial Registration</p> <p>Clinicaltrials.gov: NCT00035867</p

Targeting dissociation using cognitive behavioural therapy in voice hearers with psychosis and a history of interpersonal trauma: A case series

From Wiley via Jisc Publications RouterHistory: received 2020-01-23, rev-recd 2020-07-27, pub-electronic 2020-09-10, pub-print 2021-06Article version: VoRPublication status: PublishedAbstract: Objectives: Previous studies have suggested that dissociation might represent an important mechanism in the maintenance of auditory verbal hallucinations (i.e., voices) in people who have a history of traumatic life experiences. This study investigated whether a cognitive behavioural therapy (CBT) intervention for psychosis augmented with techniques specifically targeting dissociative symptoms could improve both dissociation and auditory hallucination severity in a sample of voice hearers with psychosis and a history of interpersonal trauma (e.g., exposure to sexual, physical, and/or emotional abuse). Design: Case series. Methods: A total of 19 service users with psychosis were offered up to 24 therapy sessions over a 6‐month intervention window. Participants were assessed four times over a 12‐month period using measures of dissociation, psychotic symptoms severity, and additional secondary mental‐health and recovery measures. Results: Sixteen participants engaged in the intervention and were included in last‐observation‐carried‐forward analyses. Dropout rates were in line with those of other CBT for psychosis trials (26.3%). Repeated measures ANOVAs revealed large and significant improvements in dissociation (drm = 1.23) and hallucination severity (drm = 1.09) by the end of treatment; treatment gains were maintained 6 months following the end of therapy. Large and statistically significant gains were also observed on measures of post‐traumatic symptoms, delusion severity, emotional distress, and perceived recovery from psychosis. Conclusions: The findings of this case series suggest that the reduction of dissociation represents a valuable and acceptable treatment target for clients with auditory verbal hallucinations and a trauma history. Future clinical trials might benefit from considering targeting dissociative experiences as part of psychological interventions for distressing voices. Practitioner points: Practitioners should consider the role of dissociation when assessing and formulating the difficulties of voice hearers with a history of trauma. Techniques to reduce dissociation can be feasibly integrated within psychological interventions for voices. Voice hearers with histories of trauma can benefit from psychological interventions aimed at reducing dissociation

Research and practice for ultra-high risk for psychosis : a national survey of early intervention in psychosis services in England

Background: Evidence from meta-analyses of randomized clinical trials show interventions for young people at ultra-high risk (UHR) of developing psychosis are effective both clinically and economically. While research evidence has begun to be integrated into clinical guidelines, there is a lack of research on the implementation of these guidelines. This paper examines service provision for UHR individuals in accordance with current clinical guidelines within the National Health Service (NHS) in England. Method: A self-report online survey was completed by clinical leaders of early intervention in psychosis (EIP) teams (N = 50) within the NHS across England. Results: Of the 50 EIP teams responding (from 30 NHS trusts), 53% reported inclusion of the UHR group in their service mandate, with age range predominantly 14 to 35 years (81%) and service provided for at least 12 months (53%). Provision of services according to NICE clinical guidelines showed 50% of services offered cognitive behavioural therapy (CBT) for psychosis, and 42% offered family intervention. Contrary to guidelines, 50% of services offered antipsychotic medication. Around half of services provided training in assessment by Comprehensive Assessment of At Risk Mental States, psycho-education, CBT for psychosis, family work and treatment for anxiety and depression. Conclusions: Despite clear evidence for the benefit of early intervention in this population, current provision for UHR within EIP services in England does not match clinical guidelines. While some argue this is due to a lack of allocated funding, it is important to note the similar variable adherence to clinical guidelines in the treatment of people with established schizophrenia

Voice-Hearing and Personification: Characterizing Social Qualities of Auditory Verbal Hallucinations in Early Psychosis

Recent therapeutic approaches to auditory verbal hallucinations (AVH) exploit the person-like qualities of voices. Little is known, however, about how, why, and when AVH become personified. We aimed to investigate personification in individuals’ early voice-hearing experiences. We invited Early Intervention in Psychosis (EIP) service users aged 16–65 to participate in a semistructured interview on AVH phenomenology. Forty voice-hearers (M = 114.13 days in EIP) were recruited through 2 National Health Service trusts in northern England. We used content and thematic analysis to code the interviews and then statistically examined key associations with personification. Some participants had heard voices intermittently for multiple years prior to clinical involvement (M = 74.38 months), although distressing voice onset was typically more recent (median = 12 months). Participants reported a range of negative emotions (predominantly fear, 60%, 24/40, and anxiety, 62.5%, 26/40), visual hallucinations (75%, 30/40), bodily states (65%, 25/40), and “felt presences” (52.5%, 21/40) in relation to voices. Complex personification, reported by a sizeable minority (16/40, 40%), was associated with experiencing voices as conversational (odds ratio [OR] = 2.56) and companionable (OR = 3.19) but not as commanding or trauma-related. Neither age of AVH onset nor time since onset related to personification. Our findings highlight significant personification of AVH even at first clinical presentation. Personified voices appear to be distinguished less by their intrinsic properties, commanding qualities, or connection with trauma than by their affordances for conversation and companionship

Continuities and Discontinuities in the Cognitive Mechanisms Associated With Clinical and Nonclinical Auditory Verbal Hallucinations

Auditory verbal hallucinations (AVHs) are typically associated with schizophrenia but also occur in individuals without any need for care (nonclinical voice hearers [NCVHs]). Cognitive models of AVHs posit potential biases in source monitoring, top-down processes, or a failure to inhibit intrusive memories. However, research across clinical/nonclinical groups is limited, and the extent to which there may be continuity in cognitive mechanism across groups, as predicted by the psychosis-continuum hypothesis, is unclear. We report two studies in which voice hearers with psychosis (n = 31) and NCVH participants reporting regular spiritual voices (n = 26) completed a battery of cognitive tasks. Compared with non-voice-hearing groups (ns = 33 and 28), voice hearers with psychosis showed atypical performance on signal detection, dichotic listening, and memory-inhibition tasks but intact performance on the source-monitoring task. NCVH participants, however, showed only atypical signal detection, which suggests differences between clinical and nonclinical voice hearers potentially related to attentional control and inhibition. These findings suggest that at the level of cognition, continuum models of hallucinations may need to take into account continuity but also discontinuity between clinical and nonclinical groups

Continuities and discontinuities in the cognitive mechanisms associated with clinical and non-clinical auditory verbal hallucinations

Auditory verbal hallucinations (AVH) are typically associated with schizophrenia but also occur in individuals without any need for care (non-clinical voice-hearers; NCVH). Cognitive models of AVH posit potential biases in source-monitoring, top-down processes, or a failure to inhibit intrusive memories. However, research across clinical/non-clinical groups is limited, and the extent to which there may be continuity in cognitive mechanism across groups, as predicted by the psychosis continuum hypothesis, is unclear. We report two studies in which voice-hearers recruited from Early Intervention in Psychosis (EIP) services (n = 31) and NCVH participants reporting regular spiritual voices (n = 26) completed the same cognitive task battery. Compared to controls (n = 33 and 28), EIP patients showed atypical signal detection, dichotic listening, and memory inhibition performance, but intact source-monitoring. NCVH participants only showed atypical signal detection, suggesting differences between clinical and non-clinical voices potentially related to attentional control and inhibition