RESUMEN
Background: Treatment-resistant schizophrenia (TRS) affects approximately 30% of people with schizophrenia. Clozapine is the gold standard treatment for TRS but is not always suitable, with a proportion of individuals intolerant of side effects or unable to engage in necessary blood monitoring. Given the profound impact TRS can have on those affected, alternative pharmacological approaches to care are needed. Objectives: To review the literature on the efficacy and tolerability of high-dose olanzapine (>20 mg daily) in adults with TRS. Design: This is a systematic review. Data Sources and Methods: We searched for eligible trials published prior to April 2022 in PubMed/MEDLINE, Scopus and Google Scholar. Ten studies met the inclusion criteria [five randomised controlled trials (RCTs), one randomised crossover trial and four open label studies]. Data were extracted for predefined primary outcomes (efficacy, tolerability). Results: Compared with standard treatment, high-dose olanzapine was non-inferior in four RCTs, three of which used clozapine as the comparator. Clozapine was superior to high-dose olanzapine in a double-blind crossover trial. Open-label studies demonstrated tentative evidence in support of high-dose olanzapine use. It was better tolerated than clozapine and chlorpromazine in two respective RCTs, and was generally well tolerated in open-label studies. Conclusion: This evidence suggests high-dose olanzapine is superior for TRS when compared with other commonly used first- and second-generation antipsychotics, including haloperidol and risperidone. In comparison with clozapine, the data are encouraging for the use of high-dose olanzapine where clozapine use is problematic, but larger, better designed trials are needed to assess the comparative efficacy of both treatments. There is insufficient evidence to consider high-dose olanzapine equivalent to clozapine when clozapine is not contraindicated. Overall, high-dose olanzapine was well tolerated, with no serious side effects. Registration: This systematic review was preregistered with PROSPERO [CRD42022312817].
RESUMEN
OBJECTIVE: The purpose of this study was to examine the epidemiology, phenomenology, and occupation-specific risk factors for suicide among regular-duty military personnel as a model for other professions at risk for workplace suicide. METHOD: Suicide incidence and methods were determined in a retrospective military cohort comprising all deaths (N=732) of regular-duty military personnel in the Irish Defence Forces between 1970 and 2002. A retrospective, case-control study using pair-matched military comparison subjects was conducted to determine occupation-specific risk factors for suicide, particularly by firearm, among military personnel. Risk factors were subjected to chi-square analysis or independent t tests and entered into a binary logistic regression analysis model. RESULTS: The period-averaged suicide rate for the cohort was 15.3/100,000. Firearm suicides accounted for 53% of the cases. Suicides that took place on duty occurred predominantly when personnel were alone shortly after duty commencement in the morning. Bivariate and logistic regression analyses identified psychiatric illness and a past history of deliberate self-harm, morning duty (shortly after duty assumption and consequent access to firearms), and a recent medical downgrading as independent risk factors predicting firearm suicide among military personnel. CONCLUSIONS: Occupation influences suicide method. Access to and opportunity to use lethal means in the workplace are distinct but related occupation-specific suicide risk factors in the military and in other at-risk professions. In professions where access to lethal means is inevitable, moderating opportunity for suicide is crucially important. In regular-duty military personnel, a medical downgrading, combined with risk factors established in civilians such as younger age, male gender, psychiatric illness, and past self-harm, increases the risk of suicide. The findings may be used to guide military harm-reduction strategies and have applicability in strategies for other professions at risk for workplace suicide.