Amisulpride, aripiprazole, and olanzapine in patients with schizophrenia-spectrum disorders (BeSt InTro): a pragmatic, rater-blind, semi-randomised trial.

BACKGROUND: Amisulpride, aripiprazole, and olanzapine are first-line atypical antipsychotics that have not previously been compared head-to-head in a pragmatic trial. We aimed to compare the efficacy and safety of these agents in a controlled trial. METHODS: This pragmatic, rater-blind, randomised controlled trial was done in three academic centres of psychiatry in Norway, and one in Austria. Eligible patients were aged 18 years or older, met ICD-10 criteria for schizophrenia-spectrum disorders (F20-29), and had symptoms of active psychosis. Eligible patients were randomly assigned to receive oral amisulpride, aripiprazole, or olanzapine. Treatment allocation was open to patients and staff, and starting dose, treatment changes, and adjustments were left to the discretion of the treating physician. Computer-generated randomisation lists for each study centre were prepared by independent statisticians. Patients were followed up for 52 weeks after random assignment, during which assessments were done 8 times by researchers masked to treatment. The primary outcome was reduction of the Positive And Negative Syndrome Scale (PANSS) total score at 52 weeks, and primary analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01446328. FINDINGS: Between Oct 20, 2011, and Dec 30, 2016, we assessed 359 patients for eligibility. 215 patients were excluded (107 did not meet inclusion criteria, 82 declined to participate, 26 other reasons). 144 patients (mean baseline PANSS total estimated score 78·4 [SD 1·4]) were randomly assigned 1:1:1 to receive amisulpride (44 patients), aripiprazole (48 patients) or olanzapine (52 patients). After 52 weeks, the patients allocated to amisulpride had a PANSS total score reduction of 32·7 points (SD 3·1) compared with 21·9 points reduction with aripiprazole (SD 3·9, p=0·027) and 23·3 points with olanzapine (2·9, p=0·025). We observed weight gain and increases of serum lipids and prolactin in all groups. 26 serious adverse events (SAEs) among 20 patients were registered (four [9%] of 44 patients allocated to amisulpride, ten [21%] of 48 patients allocated to aripiprazole, and six [12%] of 52 patients allocated to olanzapine), with no statistically significant differences between the study drugs. 17 (65%) of the 26 SAEs occurred during the use of the study drug, with readmission or protracted hospital admission accounting for 13 SAEs. One death by suicide, one unspecified death, and one life-threatening accident occurred during follow-up, after cessation of treatment. INTERPRETATION: Amisulpride was more efficacious than aripiprazole or olanzapine for reducing the PANSS total scores in adults with schizophrenia-spectrum disorders. Side-effect differences among the groups were generally small. This study supports the notion that clinically relevant efficacy differences exist between antipsychotic drugs. Future research should aim to compare first-line antipsychotics directly in pragmatic clinical trials that reflect everyday clinical practice. FUNDING: The Research Council of Norway, the Western Norway Regional Health Trust, and participating hospitals and universities.

Public attitudes towards involuntary admission and treatment by mental health services in Norway.

PURPOSE: The role of compulsory treatment of serious mental disorders has been the topic of ongoing public debate involving among others mental health professionals, service providers, service user advocates, relatives of service users, media commentators and politicians. However, relatively little is known about general public attitudes towards involuntary admission and compulsory treatment of people with various mental disorders. This article examines the attitudes in a representative sample of Norway's population towards the use of involuntary admission and treatment, and under which circumstances does the general public consider compulsory treatment to be justified in the Norwegian mental health care services. METHOD: Data were collected from a representative sample of the population in Norway aged 18 and older. The sample was stratified for gender, geographical region and age distribution (n=2001). The survey was performed in the months of May 2009 (n=1000) and May 2011 (n=1001), using Computer Assisted Telephone Interviews (CATI) by an independent polling company. All respondents were provided a general definition of coercive intervention before the interview was conducted. ANALYSIS: Univariate descriptions and bivariate analyses were performed by means of cross-tabulation, analysis of variance (one-way ANOVA) and comparing of group of means. Cohen's d was used as the measure for effect size. RESULTS: Between 87% and 97% of those surveyed expressed strong or partial agreement with the use of involuntary admissions or compulsory treatment related to specified cases and situations. The majority of interviewees (56%) expressed the opinion that overall, current levels are acceptable. A further, 34% were of the opinion that current levels are too low, while only 9.9% of respondents supported a reduction in the level of involuntary treatment. Lower levels of education were associated with a more positive attitude towards involuntary admission and treatment. There was stronger support for admission to prevent suicide than the possibility of violence by the mentally ill. CONCLUSION: The Norwegian adult population largely supports current legislation and practices regarding involuntary admission and compulsory treatment in the mental health services.

Visual Hallucinations in First-Episode Psychosis: Association with Childhood Trauma.

BACKGROUND: Hallucinations are a core diagnostic criterion for psychotic disorders and have been investigated with regard to its association with childhood trauma in first-episode psychosis samples. Research has largely focused on auditory hallucinations, while specific investigations of visual hallucinations in first-episode psychosis remain scarce. OBJECTIVES: The aims of this study were to describe the prevalence of visual hallucinations, and to explore the association between visual hallucination and childhood trauma in a first-episode psychosis sample. METHODS: Subjects were included from TIPS-2, a first episode psychosis study in south Rogaland, Norway. Based on the medical journal descriptions of the Positive and Negative Symptoms Scale (PANSS), a separate score for visual and auditory hallucinations was created (N = 204). Patients were grouped according to hallucination severity (none, mild, and psychotic hallucinations) and multinomial logistic regression was performed to identify factors associated with visual hallucination group. RESULTS: Visual hallucinations of a psychotic nature were reported by 26.5% of patients. The experience of childhood interpersonal trauma increased the likelihood of having psychotic visual hallucinations. CONCLUSION: Visual hallucinations are common in first-episode psychosis, and are related to childhood interpersonal trauma.

Verbal working memory deficits predict levels of auditory hallucination in first-episode psychosis.

BACKGROUND: Auditory verbal hallucinations are a characteristic symptom in schizophrenia. Recent causal models of auditory verbal hallucinations propose that cognitive mechanisms involving verbal working memory are involved in the genesis of auditory verbal hallucinations. Thus, in the present study, we investigate the hypothesis that verbal working memory is a specific factor behind auditory verbal hallucinations. METHODS: In the present study, we investigated the association between verbal working memory manipulation (Backward Digit Span and Letter-Number Sequencing) and auditory verbal hallucinations in a population study (N=52) of first episode psychosis. The degree of auditory verbal hallucination as reported in the P3-subscale of the PANSS interview was included as dependent variable using sequential multiple regression, while controlling for age, psychosis symptom severity, executive cognitive functions and simple auditory working memory span. RESULTS: Multiple sequential regression analyses revealed verbal working memory manipulation to be the only significant predictor of verbal hallucination severity. CONCLUSIONS: Consistent with cognitive data from auditory verbal hallucinations in healthy individuals, the present results suggest a specific association between auditory verbal hallucinations, and cognitive processes involving the manipulation of phonological representations during a verbal working memory task.