Olanzapine In Patients Research Articles

Investigating the efficacy and safety of olanzapine prophylaxis for opioid-induced nausea and vomiting (JORTC-PAL20): a study protocol for an open-label, single-arm exploratory study

IntroductionIn opioid therapy for cancer pain, opioid-induced nausea and vomiting (OINV) occur in 20%–40% of patients during initial opioid treatment or increasing opioid doses. OINV result in failure to achieve...

Initial dosage optimization of olanzapine in patients with bipolar disorder based on model-informed precision dosing: a study from the real world.

Olanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study. Thirty-nine patients with BPD from the real-world study were collected to construct the MIPD model. Weight, combined used quetiapine influenced olanzapine clearances in patients with BPD, where the clearance rates were 0.152:1 in patients with or without quetiapine under the same weight. We simulated olanzapine doses once a day or twice a day, of which twice a day was optimal. Without quetiapine, for twice-a-day olanzapine doses, 0.80, 0.70, and 0.60mg/kg/day were suitable for 40- to 56-kg BPD patients, 56- to 74-kg BPD patients, and 74- to 100-kg BPD patients, respectively. With quetiapine, for twice-a-day olanzapine doses, 0.05mg/kg/day was suitable for 40- to 100-kg BPD patients. This study was the first to investigate the optimal olanzapine initial dosage in patients with BPD via MIPD based on a real-world study, providing clinical reference for the precision medication of olanzapine in BPD patients.

Association of smoking cigarettes, age, and sex with serum concentrations of olanzapine in patients with schizophrenia.

Olanzapine is an atypical antipsychotic drug which is effective in the treatment of schizophrenia. Cigarette smoking, age, and sex could be related to the pharmacokinetics and serum concentrations of olanzapine in patients with schizophrenia. The aim of the study was to examine whether there was a significant difference in the serum olanzapine concentrations with regard to the mentioned factors. A total of 58 outpatients with schizophrenia (37 smokers, 42 men, 35 older than 40 years) participated in the study. Blood was sampled in serum tubes just before taking the next dose of olanzapine. Olanzapine was extracted by liquid-liquid extraction and was measured by an in-house high-performance liquid chromatography method on Shimadzu Prominence HPLC System with diode array detector SPD-M20A (Shimadzu, Kyoto, Japan). The results were expressed as the ratio of concentration to the daily dose of olanzapine (C/D). Non-parametric statistical tests were used to analyse differences between variables. The median C/D of olanzapine (interquartile range) in smokers was 6.0 (3.4-10.2) nmol/L/mg and in non-smokers 10.1 (5.9-17.6) nmol/L/mg; P = 0.007. The median C/D of olanzapine in patients younger than 40 years was 5.6 (4.5-10.2) nmol/L/mg and in patients older than 40 years 8.4 (5.6-13.0) nmol/L/mg; P = 0.105. The median C/D of olanzapine in male patients was 6.6 (4.6-10.4) nmol/L/mg and in female patients 9.0 (5.9-15.3) nmol/L/mg; P = 0.064. The serum olanzapine concentration was significantly lower in smoking than in non-smoking patients with schizophrenia. No significant difference was demonstrated with regard to age and sex.

Efficacy and Side Effects of Aripiprazole and Olanzapine in Patients with Psychotic Disorders: A Randomized Controlled Trial.

In clinical experience, selecting atypical antipsychotics optimally balancing their benefits and potential side effects is seen to improve treatment adherence in patients. This study aimed to compare the effectiveness and side effect profiles of aripiprazole and olanzapine in patients with psychotic disorders. In this double-blind clinical trial, the subjects were patients with psychotic disorders treated with aripiprazole and olanzapine. The subjects were randomly divided into two equally sized groups. One group was treated with olanzapine and the other group with aripiprazole. All participants were assessed using the positive and negative syndrome scale and side effects were monitored over a two-month follow-up period. The participants comprised N = 76 patients (65 male; 11 female). Treatments with both aripiprazole (n = 38) and olanzapine (n = 38) were associated with a significant decrease in the severity of psychotic symptoms over the two-month treatment period. This decrease was achieved faster in the olanzapine group. There were no significant differences in the changes in body mass index, waist circumference, blood sugar, triglyceride, or cholesterol between the two groups. A qualitative difference between the groups was found in their total sleep duration. Olanzapine was more effective than aripiprazole in reducing psychotic symptoms. There were no significant differences between the overall side effect profiles of the two drugs.

Effects of varenicline on the serum levels of olanzapine in male patients with Schizophrenia: a randomized controlled trial.

Smoking in patients with Schizophrenia is more common than in the general population. Varenicline, a partial agonist at α4β2 nicotinic acetylcholine receptors, is an effective smoking cessation pharmacotherapy in patients with Schizophrenia. However, its effects on the serum levels of antipsychotics in Schizophrenia are understudied. This study investigated the impact of smoking cessation with varenicline on the serum concentration of olanzapine in patients with Schizophrenia. Adult smokers with Schizophrenia were enrolled in a 12-week course of varenicline and placebo for smoking cessation. The serum concentration of olanzapine was measured at baseline and weeks 1, 2, 4, 8, and 12. Data were analyzed with the generalized additive mixed model. During the 12-week study, the results indicated that olanzapine concentrations increased nonlinearly in the varenicline and placebo groups. Threshold effect analysis suggested that the olanzapine concentrations increased over time until the turning point (week 4). However, there was no significant difference between the two treatment groups. Varenicline showed safety and efficacy in smoking cessation in people with Schizophrenia.

Does drug use affect the efficacy of amisulpride, aripiprazole and olanzapine in patients with schizophrenia spectrum disorders? Results from a pragmatic, randomised study

ObjectivesDrug use is prevalent in patients with schizophrenia spectrum disorders (SSD) but there is limited knowledge about the influence of drug use on the effectiveness of antipsychotic medication. This secondary explorative study compared the effectiveness of three antipsychotics in patients with SSD, with and without drug use. MethodsThe BeSt InTro multi-centre, head to head, rater-blinded randomised study compared amisulpride, aripiprazole and olanzapine over a 1-year follow-up period. All patients (n = 144) were aged ≥18 years and met the ICD-10 criteria for SSD (F20–29). Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The primary outcome was reduction of a PANSS positive subscale score. ResultsAt baseline, 38% of all patients reported drug use in the last 6 months before inclusion, with cannabis as the main drug (85%), followed by amphetamine-type stimulants (45%), sedatives (26%), hallucinogens (19%), cocaine (13%), opiates (4%), GHB (4%), solvents (4%), analgesics (4%) and anabolic steroids (2%). The predominant pattern was the use of several drugs. There were no significant overall differences in the PANSS positive subscale score reduction for the three studied antipsychotics among patients either with or without drug use. In the drug use group, older patients treated with amisulpride showed a greater PANSS positive subscale score reduction during the treatment period compared to younger patients. ConclusionThe current study showed that drug use does not appear to affect the overall effectiveness of amisulpride, aripiprazole and olanzapine in patients with SSD. However, amisulpride may be a particularly suitable choice for older patients with drug use.

Comparative Assessment of Effect on Psychomotor Performance Efficacy and Adherence of Levosulpiride and Olanzapine in Patients with Schizophrenia: A Parallel, Open-label, Prospective Observational Study

Abstract Context: Schizophrenia is mostly treated with atypical antipsycotics, which may be required for lifetime. Olanzapine is commonly used in this condition, whereas levosulpiride is approved in India for the same. Knowing the effect of these drugs on psychomotor function helps in choosing a suitable drug to a particular patient based on his daily activities. Aims: The aim is to compare the effect of levosulpiride and olanzapine on psychomotor performance, efficacy, and adherence in patients with schizophrenia. Settings and Design: This was open-label, parallel arm, prospective observational study carried out in a tertiary care hospital of central India from December 2019 to December 2021. Subjects and Methods: Thirty-six patients visiting psychiatry OPD, diagnosed by treating psychiatrist as schizophrenia were assessed by CFFT, hand steadiness test (HST), arithmetic ability test, and reaction time (RT) for psychomotor function, and symptoms were scored on positive and negative syndrome scale (PANSS) and brief negative symptom scale (BNSS) rating scales at the first visit, end of 4 and 8 weeks. Adherence was assessed by the Medication adherence rating scale at 8 weeks. Results: Statistically significant increase in RT was seen in both levosulpiride (P = 0.04) and olanzapine (P = 0.0065) groups, whereas only the olanzapine group had a significant change in CFFT (P = 0.04) and HST (P = 0.01) at 8 weeks. On head-to-head comparison, a statistically significant worsening in HST score (P = 0.01) was seen in olanzapine group. Both the groups had significant decreases in all PANSS (P < 0.001) and BNSS (P < 0.001) scores. When change in PANSS and BNSS scores were compared with each other, the levosulpiride group had a significantly more decrease in scores on PANSS negative scale (P = 0.03). Patients in both groups were adherent to treatment. Conclusions: Our study concluded that levosulpiride is better than olanzapine on its fine motor control. Both the drugs increase RT while only olanzapine worsened fine motor control and CFF. Both the drugs were effective for schizophrenia with 8 weeks treatment, while levosulpiride is superior to olanzapine in improving negative symptoms of schizophrenia.

Efficacy of Olanzapine in Anxiety Dimension of Schizophrenia: A Systematic Review of Randomized Controlled Trials.

Anxiety symptoms and anxiety disorders are frequent in patients with schizophrenia and are associated with greater severity of both positive and negative symptoms, cognitive impairment, poorer functioning and quality of life. Accumulating evidence suggests that atypical antipsychotics may have a role in treating comorbid anxiety symptoms. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting randomized control trials (RCTs) that evaluated efficacy of olanzapine on anxiety symptoms in patients diagnosed with schizophrenia and included anxiety evaluation scales. We searched PubMed and Web of Science databases for articles in English language available until September 2021. We selected 7 studies (3 with primary data analysis, 4 with secondary data analysis) regarding the use of olanzapine in patients with schizophrenia. In fours studies olanzapine was superior to haloperidol in improving anxiety symptoms. Four studies compared olanzapine versus risperidone: in two of them risperidone was superior to olanzapine, although one study was limited by a relatively small sample size. In the other two there were no significant differences between olanzapine and risperidone-treated patients. One study found that olanzapine and clozapine were comparable in terms of efficacy. Although olanzapine was superior to haloperidol in treating anxiety, this symptom was a secondary outcome measure in most of the considered studies. Future RCTs comparing different antipsychotics and larger sample sizes may allow to develop more solid treatment strategies.

Population pharmacokinetics and dosing optimization of olanzapine in Chinese paediatric patients: Based on the impact of sex and concomitant valproate on clearance.

Olanzapine is an atypical antipsychotic drug used for mental disorders. There are limited studies providing sufficient pharmacokinetic data, thus the variability of concentrations of olanzapine used in Chinese paediatric patients aged 10 to 17 years remains to be evaluated. Therapeutic drug monitoring data were collected from 151 paediatric patients aged 10 to 17 years who received olanzapine. The model was developed with a NONMEM software program. The final model validation and evaluation were assessed by bootstrap, diagnostic scatter plots, and normalized prediction distribution error (NPDE). Regimens of different dosages were simulated to reach the target concentration levels of 20 ng/ml, by using the final model with typical parameters. The one-compartment model was considered the best fit for the data. Typical estimates of the absorption rate constant (Ka), apparent clearance (CL/F), and apparent distribution volume (V/F) in the final model were 0.142 h-1 , 15.4L/h, and 322 L, respectively. Sex and concomitant valproate (VPA) were included as significant predictors of olanzapine clearance, which was described by the following equation: CL/F=15.4 × (1 + 0.546 × SEX) × (1 + 0.264 × VPA). Results of Monte-Carlo simulation suggested that male paediatric patients with concomitant VPA were advised to take no less than 15 mg per day of olanzapine orally, and in female paediatric patients with concomitant VPA, a dosing regimen of 10mg may be sufficient to achieve the therapeutic range of olanzapine. Our results identified concomitant valproate and sex as significant covariates in olanzapine population pharmacokinetics. Our model may be a useful tool for recommending dosage adjustments for physicians. The pharmacokinetics of olanzapine in patients aged 10 to 17 years was generally similar to that of adults and the elderly.

Off-label use of antidepressants, antipsychotics, and mood-stabilizers in psychiatry.

Off-label drug prescribing in psychiatry is increasing. Many psychotropic drugs are approved for psychopathologic syndromes rather than based on international standard diagnostic classification systems which might facilitate the clinical decision for off-label prescriptions. The objective of this study was to analyze the prevalence and category of off-label use of psychotropic drugs. The study was conducted in 10 psychiatric hospitals in Germany over a period of 2years. Prescription data of all patients were retrospectively analyzed after identification of antidepressants, antipsychotics, and mood-stabilizers, which were classified as off-label according to the German prescribing information and diagnostic classification according to ICD-10. In total, 53,909 patient cases (46% female) with a mean age of 46.8 (SD: 18) years were included in the study. 30.2% of the cases received at least one off-label prescription of a psychotropic drug during hospital stay. Off-label prevalence rates differed markedly between different diagnostic groups (ICD-10 F0/G3: 47%, F1: 33%, F2: 25%, F3: 21%, F4: 27%, F6: 46%, F7: 84%). The most often off-label prescribed drugs were quetiapine and mirtazapine for organic mental disorders (F0/G3), valproate and quetiapine in patients with disorders due to psychoactive substance use (F1), valproate in patients with psychotic disorders (F2), and risperidone and olanzapine in patients with affective disorders (F3). The prevalence rate of psychotropic off-label prescriptions is high if restricted to product description and ICD-10 diagnosis. Therefore, current psychiatric guidelines should drug-specifically issue this problem by defining psychiatric off-label indications based on a clear benefit-risk assessment.

Samidorphan for the treatment of weight gain associated with olanzapine in patients with schizophrenia and bipolar disorder

ABSTRACT Introduction Olanzapine (OLZ) is one of the most effective antipsychotic agents, however, its clinical utility has been limited by weight gain. Samidorphan (SAM) is a μ-opioid receptor antagonist and it can reduce the weight gain associated with OLZ. A combination of OLZ and SAM (OLZ/SAM) has been developed to provide the antipsychotic efficacy of OLZ, while mitigating OLZ-associated weight gain. Areas covered A comprehensive literature search was conducted in PubMed. Key search terms included SAM and weight gain associated with OLZ. The pharmacological action, clinical efficacy, and safety of SAM were reviewed. Expert opinion OLZ can lead to weight gain. SAM is a new drug that acts as an opioid receptor antagonist that can decrease weight gain. SAM mitigates OLZ-associated weight gain while preserving the antipsychotic efficacy of OLZ. Clinical trials have confirmed that OLZ/SAM significantly improved psychotic symptoms, and resulted in significantly less weight gain than OLZ. OLZ/SAM was well tolerated. Therefore, it is a potential new treatment option for schizophrenia.

Increasing the use of olanzapine in patients receiving chemotherapy in a community oncology practice.

12123 Background: The addition of olanzapine to high emetic risk chemotherapy regimens substantially improves nausea and vomiting within 24 hours and is recommended in the guidelines of both the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). However, the uptake of olanzapine has been low in national and institutional settings. The purpose of this project was to increase guideline-concordant prescribing of olanzapine in eligible patients in a community oncology practice. Methods: We developed a multiphase program to address the barriers to the use of olanzapine in a community oncology practice. Patients’ medical records (N = 423) were reviewed to collect baseline data. Motivational interviewing with prescribing clinicians elicited barriers to prescribing, reinforced clinical guidelines, and elicited and reinforced language that suggested a willingness to change prescribing patterns. Chemotherapy protocols were subsequently updated to include olanzapine for high emetic chemotherapy regimens, and prescriber and nurse education was provided by our pharmacists regarding the most recent ASCO and NCCN guidelines. A fellow-led educational session was provided to the infusion nursing team and care managers. At the end of a seven-month period, prescribing information was identified through a system-generated report followed by a medical record review for validation (N = 136) and was shared monthly with prescribing clinicians. Results: At baseline, the use of olanzapine was zero. Multiple barriers were identified regarding the use of olanzapine during motivational interviewing with clinicians, including lack of knowledge of the guidelines, belief that most patients do not require olanzapine, concerns about sedation with the previously recommended dose of 10 mg, and order sets that did not include olanzapine. After the interventions, there was a statistically significant increase in the use of olanzapine from 0% to 56% (p-value < 0.001). Conclusions: A combination of motivational interviewing, prescriber and nurse information support, and changes to the pre-populated order sets for chemotherapy antiemetics was highly successful in improving the uptake of guideline-concordant prescribing of antiemetics. This model of quality improvement, including motivation interview, may support quality improvement efforts across oncology.[Table: see text]

Metabolic Side Effects of Olanzapine in Patients With Psychotic Disorders in Oman: A Retrospective Cohort Study.

We evaluated the impact of olanzapine on metabolic changes in patients with psychotic disorders. This was a retrospective cohort study involving patients prescribed olanzapine and attending Sultan Qaboos University Hospital (Muscat, Oman). Patients were followed up retrospectively from March 2006 until April 2021. Cardiovascular treatment targets were evaluated as per the 2019 European Society of Cardiology guidelines. We enrolled 253 patients (mean age: 40±17 years). Olanzapine monotherapy was associated with increased body weight (+8kg; 95% confidence interval (CI): 6-9; P < .001), body mass index (+3kg/m2; 95% CI: 2-4; P < .001), total cholesterol (+.4mmol/L; 95% CI: .3-.5; P < .001), low-density lipoprotein cholesterol (LDL-C) (+.3mmol/L; 95% CI: .1-.4; P < .001), fasting triglycerides (+.2mmol/L; 95% CI: .1-.3; P<.001), fasting glucose (+.6mmol/L; 95% CI: .4-.7; P< .001), HbA1c (+.3%; 95% CI: .2-.4; P < .001), systolic blood pressure (BP) (+9 mmHg; 95% CI: 6-12; P < .001) and diastolic BP (+4 mmHg; 95% CI: 2-6; P < .001) levels. Cardiovascular therapeutic goals were attained in 38% (n = 97), 61% (n = 154), 71% (n = 180), and 59% (n = 150) for LDL-C, non-high-density lipoprotein cholesterol, triglycerides, and BP, respectively. Olanzapine was associated with adverse metabolic changes. Therefore, many patients were not at their target cardiovascular treatment goals.

LBA63 Placebo-controlled, double-blinded phase Ⅲ study comparing dexamethasone on day 1 with dexamethasone on days 1 to 4, with combined neurokinin-1 receptor antagonist, palonosetron, and olanzapine in patients receiving cisplatin-containing highly emetogenic chemotherapy: SPARED trial

Olanzapine (OLZ) 5 mg combined with dexamethasone (DEX), neurokinin-1 receptor antagonist (NK1-RA), and palonosetron (PALO) has been established as the standard for patients (pts) receiving cisplatin (CDDP)-containing highly emetogenic chemotherapy (HEC). This study aimed to clarify the non-inferiority of DEX sparing when combined with NK1-RA, PALO, and OLZ in CDDP-containing HEC.

Amisulpride: What’s Old Can Be New in the United States

Amisulpride: What’s Old Can Be New in the United States

High-dose olanzapine in treatment resistant schizophrenia. A case report and literature review

ObjectiveWe report a case of a 58-year-old gentleman who was hospitalised intermittently for one year due to treatment resistant schizophrenia. Prior to hospitalisation he had been prescribed standard antipsychotics for decades without full resolution of positive psychotic symptoms. During his final admission lasting six months he was guarded, suspicious, irritable, constantly paced the corridor and displayed thought block and paranoid persecutory delusions. He would not enter the assessment room or allow any blood or ECG monitoring, however, he was compliant with oral medication. He was successfully treated with high dose olanzapine (40mg/day) and was discharged to the community. The aim of this study is to bring awareness and add to the body of evidence for the use of high-dose olanzapine in patients with treatment resistant schizophrenia in whom a trial of clozapine is not possible.Case reportThe patient gave written consent for this case report to be written and presented. An extensive literature review was performed and key papers were identified. Discussion focuses on the key areas in the literature.DiscussionThis case demonstrates that high-dose olanzapine can be used effectively as an alternative to clozapine in treatment resistant schizophrenia.ConclusionThis case highlights the need for further evaluation of high-dose olanzapine as an alternative to clozapine in patients with treatment-resistant schizophrenia.

A phase II study of the safety of olanzapine for oxaliplatin based chemotherapy in coloraectal patients

Olanzapine has exhibited efficacy as an antiemetic agent when used with 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists for patients receiving highly emetogenic chemotherapy. In addition, several studies have reported the efficacy or safety of olanzapine in patients receiving moderately emetogenic chemotherapy, including carboplatin, irinotecan, and oxaliplatin. However, no reports of olanzapine use have focused on patients receiving oxaliplatin-based chemotherapy. Therefore, we analyzed the safety of antiemetic therapy using olanzapine, palonosetron, aprepitant, and dexamethasone in colorectal cancer patients undergoing oxaliplatin-based chemotherapy. This study was a prospective phase II single-institution study of 40 patients (median age 60 years, 23 patients were male). The primary endpoint was the incidence of adverse events, and the exploratory endpoints were the rate of chemotherapy-induced nausea and vomiting. Almost all patients (90%) had a performance status of 0. All patients received the scheduled antiemetic therapy. The most common adverse event was somnolence (n = 7 patients, 17.5%). All adverse events were grade 1. Thirty-six patients were included in the exploratory analysis of efficacy. No patients experienced vomiting during the first 120 h after chemotherapy, and complete response and complete control were both 86.1%. The rate of total control was 55.6% during the same time period. Olanzapine use with 5-HT3 receptor antagonists, dexamethasone, and NK1 receptor antagonists was safe for colorectal cancer patients receiving oxaliplatin-based chemotherapy.

Study protocol for SPARED trial: randomised non-inferiority phase III trial comparing dexamethasone on day 1 with dexamethasone on days 1–4, combined with neurokinin-1 receptor antagonist, palonosetron and olanzapine (5 mg) in patients receiving cisplatin-based chemotherapy

IntroductionDexamethasone (DEX) is administered for multiple days to prevent chemotherapy-induced nausea and vomiting for patients receiving highly emetogenic chemotherapy (HEC); however, its notorious side effects have been widely reported. Although...

Delirium treatment in intoxicated patients in ICU: A randomized, double-blind clinical trial

Objective: Delirium is one of the most common complications in patients admitted to intensive care units (ICUs). Delirium is a definite cause for more extended hospital stays, higher mortality rates, and possibly persistent cognitive decline in the future. Antipsychotics have been frequently evaluated as first drugs of choice, but the most appropriate, evidence-based treatment is yet to be discovered. This study aims to compare the efficacy of haloperidol and olanzapine in patients admitted to our toxicology ICU. Methods: This double-blind, randomized controlled clinical trial was undertaken on 35 ICU admitted patients with delirium in Loghman Hakim hospital in Tehran, Iran. The diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for delirium, and clinical toxicologists included the patients according to the study’s inclusion and exclusion criteria. Patients received either haloperidol or olanzapine based on computerized randomization. The severity of delirium was measured with the Memorial Delirium Assessment Scale (MDAS) scoring on days 0 and 3 of ICU-admission. Results: The total sample size was 35 in which 16 patients received haloperidol, and 19 patients received olanzapine. The doses of haloperidol and olanzapine were 3 mg three times a day and 5 mg three times a day, respectively. There was no significant difference in baseline characteristics and the scores of MDAS between groups. Conclusion: Olanzapine and haloperidol have the same efficacy in the management of delirium in toxicology ICU-admitted patients. They can be interchangeably used for delirium treatment in these patients.

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

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. 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. 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. 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. The Research Council of Norway, the Western Norway Regional Health Trust, and participating hospitals and universities.