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Summary 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.

Introduction: Psychosis is a multifaceted clinical phenomenon in which the various symptoms may show a differential response to treatment. Important information may be lost when heterogeneous sympt...

Background Antipsychotic associated akathisia is a highly relevant clinical phenomenon. The common side effect can be stigmatizing, cause subjective distress and depression, lead to medication noncompliance and be potentially disabling for patients with psychosis. Associations between akathisia and both suicide, depression and agitation has been suggested in research literature, but inconsistently. This study investigates the level of akathisia at hospital discharge/first follow-up for consecutively admitted patients with acute phase psychosis, comparing four atypical antipsychotics (AAPs) regarding the presence of akathisia, and explores possible associations between akathisia and both suicidality, depression and agitation. Methods This study is a sub-study of the Bergen Psychosis Project (BPP), a pragmatic, rater-blind, randomized trial comparing head-to-head ziprasidone, olanzapine, risperidone and quetiapine. The present study reports cross-sectional data at discharge/first follow-up after acute admission to hospital for patients with psychosis. Patients were assessed with The Positive And Negative Syndrome Scale (PANSS). We applied the validated PANSS Excited Component (PANSS-EC) factor to assess agitation. The PANSS-EC consists of the five PANSS items: P4 Excitement, P7 Hostility, G4 Tension, G8 Uncooperativeness and G14 Poor impulse control. To assess depression in general and suicidality specifically we used the validated Calgary Depression Scale for Schizophrenia (CDSS).Furthermore the Clinical Global Impression – Severity Scale (CGI-S), and the patient-administered version of the UKU Side Effect Self-Rating Scale (UKU SERS Pat). Results A total of 109 patients were included of which 35 (32.1 %) were females, mean age was 34.0 (12.4). The mean total PANSS score was 54.9 (14.4), the mean CGI-S was 3.7 (1.1) and the mean total CDSS score was 3.9 (4.0). Our preliminary results show that a total of 58 (53.3%) patients had used antipsychotics before entering the study. Some level of akathisia was reported by ¼ of the patients, meaning a score of 1 or more on the UKU SERS Pat. There was a statistically significant difference between ziprasidone and olanzapine, with higher akathisia level in the ziprasidone group. Furthermore, there were statistically significant correlations between akathisia and suicidality and between akathisia and depression. We found no significant correlation between akathisia and the PANSS-EC factor or between akathisia and the PANSS general item G14 Poor impulse control. Statistical details will be presented on the poster. Discussion Our study shows that akathisia is a prevalent side effect in a clinically relevant sample of patients with acute phase psychosis treated with atypical antipsychotics. The prevalence of antipsychotic associated akathisia ranges widely across studies due to, among others, methodological heterogeneities and varieties in measurement tools. In our study, akathisia was significantly associated with both depression and suicidality. The finding of a significant correlation between akathisia and suicidality supports a previous finding that even a mild to moderate experience of akathisia in first episode patients had an increase in the likelihood to be suicidal. We found no relationship with agitation in our study. As akathisia may go unrecognized in clinical practice and may contribute to medication noncompliance, systematic assessment for symptoms of akathisia is warranted. Conclusion Akathisia is still a prevalent phenomenon in a substantial proportion of patients treated with atypical antipsychotics. Special attention is called for regarding the association towards suicidality.