The use of network pharmacology and blood metabolomics to study the pathogenesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment plans.

To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent aggression.

Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment, and the related metabolic pathways were identified. Network pharmacology was used to establish protein-protein interaction networks of the core targets of olanzapine. Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently performed.

Compared with the healthy group, the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways, among which the key pathways were the alanine, aspartate and glutamate metabolism and arginine biosynthesis pathways. After treatment with olanzapine, the levels of 10 differentially abundant metabolites were significantly reversed in patients with schizophrenia. Olanzapine effectively regulated six metabolic pathways, among which the key pathways were alanine, aspartate and glutamate metabolism and arginine biosynthesis pathways. Ten core targets of olanzapine were involved in several key pathways.

The metabolic pathways of alanine, aspartate, and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.

The aim of this study was to evaluate discontinuation and hospitalization rates in patients with schizophrenia spectrum disorder who were treated with long-acting injectable (LAI) antipsychotics. We recorded clinical data about the period before the LAI treatment, when LAI treatment was initiated, and during the LAI treatment. Variables related to early (<8 weeks) and other LAI discontinuations and hospitalization were analyzed. Out of 452 patients, 14.4% of them discontinued their LAI treatment before 8 weeks, another 24.8% of the patients stopped their LAI by themselves later. Early discontinuers were younger, had shorter duration of illness, and less educated. Sixty-two (27.2%) of the patients were hospitalized under LAI treatment and 40% of the hospitalizations occurred in initial 6 months. Rate of hospitalization was 36.1% in the group who discontinued LAI after 8 weeks. In logistic regression analysis, younger age, history of combined antipsychotic treatment, number of hospitalizations before LAI, use of LAI for less than 6 months and alcohol abuse under LAI treatment were found related to hospitalization. Our findings suggested that discontinuation and hospitalization are still common among the patients who were treated with LAI antipsychotics.

Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia.

Postinjection delirium/sedation syndrome (PDSS) has been reported uncommonly during treatment with olanzapine long-acting injection (LAI), a sustained-release formulation of olanzapine.

The primary aim of the study was to estimate the incidence per injection and per patient of PDSS events in adult patients with schizophrenia who were receiving olanzapine LAI in real-world clinical practice. Secondary aims were to further characterise the clinical presentation of PDSS events, to identify potential risk factors associated with PDSS events and to characterise hospitalisations at baseline and post-baseline.

A prospective observational study of adult patients with schizophrenia receiving olanzapine LAI from 24 countries. Data were collected on patient characteristics, olanzapine LAI treatment and any adverse events (AEs). All AEs were reviewed and adjudicated for PDSS using predetermined criteria.

There were 46 confirmed PDSS events (0.044% of the 103 505 injections) in 45 patients (1.17% of the 3858 patients). Based on 45 confirmed events with time-to-onset information, 91.1% (n=41) occurred within 1 h of injection. Time-to-recovery from the event was within 72 h for 95.6% of patients (range 6 h to 11 days). Risk factors for PDSS (per-injection) included high dose (odds ratio (OR)_high/low=3.95; P=0.006) and male gender (OR_female/male=0.42; P=0.017).

Results of this study confirm previously reported PDSS rates, time to onset and recovery, and the severity of PDSS events, and suggest that higher doses and male gender are potential risk factors associated with PDSS.

All authors are full-time employees and hold stock/stock options in Eli Lilly, which funded this study. This post-authorisation safety study (PASS) was proposed by Eli Lilly when submitting the original marketing authorisation application for olanzapine LAI in 2007. The protocol and final study report for this European Union regulatory commitment are publicly accessible via the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) European Union PASS Register (www.encepp.eu/encepp/viewResource.htm?id=16847). The current manuscript describes the results within the final study report.

© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

After 1 year of introduction of olanzapine long-acting injectable (LAI) in India, many psychiatrists believe that it is a very affordable, well-tolerated, and effective second generation long-acting antipsychotic depot compared to not well tolerated but cheap first generation antipsychotic depots and to other second generation depots which are costly. However, reports of its possible adverse events in clinical settings are not yet published. We report what probably might be the first case of postinjection delirium/sedation syndrome (PDSS) in India. Although the occurrence is uncommon, incorrect understanding of this event may hinder the future use of the potentially useful olanzapine LAI. We review the available literature on the proposed diagnostic guidelines, mechanism of this event, precautions, and management of PDSS.