Safety and effectiveness of olanzapine and droperidol for chemical restraint for non-consenting adults: a systematic review and meta-analysis.

BACKGROUND: Chemical restraint (CR) is emergency drug management for acute behavioural disturbances in people with mental illness, provided with the aim of rapid calming and de-escalating potentially dangerous situations. AIMS: To describe a systematic review of Randomised Controlled Trials (RCTs) reporting on short-term safety and effectiveness of drugs used for CR, administered to non-consenting adults with mental health conditions, who require emergency management of acute behavioural disturbances. A meta-analysis was conducted of those RCTs with comparable interventions, outcome measures and measurement timeframes. METHOD: Academic databases were searched for RCTs published between 1 January 1996 and 20th April 2020. Relevant RCTs were critically appraised using the 13-item JBI checklist. All RCTs were described, and step-wise filters were applied to identify studies suitable for meta-analysis. For these, forest and funnel plots were constructed, and Q and I2 statistics guided interpretation of pooled findings, tested using MedCalc Version 19.1. RESULTS: Of 23 relevant RCTs, 18 (78.2% total) had excellent methodological quality scores (at least 90%). Eight RCTs were potentially relevant for meta-analysis (six of excellent quality), reporting 20 drug arms in total. Adverse events for 6-36% patients were reported in all 20 drug arms. Four drug arms from two homogenous studies of N = 697 people were meta-analysed. These RCTs tested two antipsychotic drugs (droperidol, olanzapine) delivered intravenously in either 5 mgs or 10 mg doses, with outcomes of time to calm, percentage calm within five or 10 min, and adverse events. There were no significant differences between drug arms for either measure of calm. However, 5 mg olanzapine incurred significantly lower risk of adverse events than 10 mg olanzapine (OR 0.4 (95%CI 0.2-0.8)), although no dose differences were found for droperidol. CONCLUSION: 5 mg intravenous olanzapine is recommended for quick, safe emergency management of people with acute behavioural disturbances associated with mental illness.

The use of olanzapine as an antiemetic in palliative medicine: a systematic review of the literature.

BACKGROUND: Olanzapine is an atypical antipsychotic that has affinity for many central nervous system receptors. Its efficacy is supported by several studies in the prevention and treatment of chemotherapy-induced nausea and vomiting. No recommendations exist on the antiemetic use of olanzapine in the palliative care setting. The aim of this work is to complete the initial work of Fonte et al. published in 2015, to determine whether the literature supports the use of olanzapine as an antiemetic in palliative situations and, in practice, to propose a therapeutic schema adapted to the palliative setting. METHODS: Systematic review of the literature according to the PRISMA criteria. We searched the PubMed, Cochrane, RefDoc, EMBase databases and the gray literature databases. The bibliographic search was conducted between November 2016 and August 2017. RESULTS: Thirteen articles were included: 2 case studies, 3 case series, 3 retrospective studies, 2 prospective studies, 2 literature reviews. All studies concluded on the efficacy of olanzapine as an antiemetic in the palliative care setting. No serious adverse effects were reported. Based on the data from the literature review, we propose a therapeutic scheme adapted to the palliative care context. CONCLUSION: Action of olanzapine on many receptors and its tolerance profile make it an interesting antiemetic treatment in palliative medicine. But to date, studies are scarce and have a low statistical power. Further investigation is therefore needed to determine the benefit of this treatment in palliative care patients, compared to usual treatments.

Optimized UPLC-MS/MS method for the quantitation of olanzapine in human plasma: application to a bioequivalence study.

Aim: Olanzapine (OLZ) is the first-line, cost-effectiveness treatment for schizophrenia in China. A quantitative ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determination of OLZ in human plasma was developed. Results: LC separation was achieved on Waters XBrige C18 column. ESI+ was involved and multiple reaction monitoring transitions were at m/z 313.2→256.1 for OLZ and m/z 316.2→256.1 IS (d3-OLZ). The linear range was 0.1-20 ng/ml with LLOQ of 0.1 ng/ml. Accuracy and precision were within 10%. The validated method was successfully applied to a bioequivalence study of OLZ disintegrating tablets at dose of 5 mg with 100% reproducibility evaluated by incurred sample reanalysis. Conclusion: A robust validated method was developed for quantitation of OLZ in human plasma.