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OBJECTIVE: Investigators have reported that weight gain attributed to clozapine is associated with its clinical response. However, weight gain is a nonspecific physiological variable that, in itself, does not explain the mechanism underlying this relation. Alternatively, other biological variables that are often associated with weight gain, such as serum lipids, may assist in explaining this observation. The primary objective of this study was to determine whether an increase in serum lipids is associated with improvement in schizophrenia symptoms during steady state treatment with clozapine. METHODS: The data for this study represent a subset of data from a randomized, double-blinded trial that evaluated subjects with schizophrenia who demonstrated a poor treatment response to clozapine. While continuing their clozapine therapy, subjects were randomly assigned to receive either risperidone 3 mg daily or placebo for 8 weeks. This course of treatment was followed by an optional (open-label) 18 weeks of augmentation with risperidone. In the present study, we included all subjects from the previously reported trial who had fasting lipid analyses and Positive and Negative Syndrome Scale (PANSS) scores from days 7 and 63 (n = 55). For the primary analyses, we used multiple regression to examine the association between serum lipid concentrations and PANSS scores, after controlling for weight. RESULTS: The analyses showed that the change in serum lipid concentration predicted change in symptoms over that of change in weight. Specifically, an increase in serum triglyceride concentration was associated with a decrease in the total PANSS score (p = 0.037). In addition, an increase in either serum total cholesterol concentration (p = 0.007), serum triglyceride concentration (p = 0.017) or their combined effect (p = 0.010) was associated with a decrease in PANSS negative subscale scores. CONCLUSION: Elevation of serum lipids is associated with an improvement in schizophrenia symptoms in subjects treated with clozapine. Although the mechanism is unclear, serum lipids may play a role in influencing clozapine's therapeutic activity. [ABSTRACT FROM AUTHOR]

Background: Homeless or precariously housed individuals live with poor health and experience premature mortality compared with the general population, yet little is known about age-related brain changes among these individuals. We evaluated whether MRI measures of brain structure are differentially associated with age and selected risk factors among individuals who are homeless or precariously housed compared with a general population sample., Methods: We compared T1-weighted and diffusion tensor imaging measures of brain macrostructure and white matter microstructure in a well-characterised sample of 312 precariously housed participants with a publicly available dataset of 382 participants recruited from the general population. We used piecewise and multiple linear regression to examine differential associations between MRI measures and between the samples, and to explore associations with risk factors in the precariously housed sample., Results: Compared with the general population sample, older age in the precariously housed sample was associated with more whole-brain atrophy (β=-0.20, p=0.0029), lower whole-brain fractional anisotropy (β=-0.32, p<0.0001) and higher whole-brain mean diffusivity (β=0.69, p<0.0001). Several MRI measures had non-linear associations with age, with further adverse changes after age 35-40 in the precariously housed sample. History of traumatic brain injury, stimulant dependence and heroin dependence was associated with more atrophy or alterations in white matter diffusivity in the precariously housed sample., Conclusions: Older age is associated with adverse MRI measures of brain structure among homeless and precariously housed individuals compared with the general population. Education, improvements in care provision and policy may help to reduce the health disparities experienced by these individuals., Competing Interests: Competing interests: TF is supported by a Sauder Family/Heart and Stroke Professorship of Stroke Research, the Heart and Stroke Foundation of Canada and the Michael Smith Foundation for Health Research. FV-R receives research support from CIHR, Brain Canada, Michael Smith Foundation for Health Research, Vancouver Coastal Health Research Institute and Weston Brain Institute for investigator-initiated research, philanthropic support from the Seedlings Foundation, in-kind equipment support for this investigator-initiated trial from MagVenture, and has received honoraria for participation in an advisory board for Janssen. WH has received consulting fees from Translational Life Sciences, Guidepoint and AbbVie for work unrelated to the Hotel Study. All other authors have no disclosures., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The rapid control of patients presenting to the emergency department (ED) with psychomotor agitation and violent behavior is paramount for the safety of patients and ED staff. The use of intramuscular (IM) ketamine in the pre-hospital and ED settings has demonstrated promising preliminary results to provide rapid and safe behavioral control. A prospective, randomized controlled trial is required to measure the potential superiority of IM ketamine compared to current standard care (IM benzodiazepines plus antipsychotics)., Methods: This will be a parallel, prospective, randomized, controlled trial of 5 mg/kg IM ketamine compared to a combination of 5 mg IM midazolam and 5 mg IM haloperidol. The study will enroll approximately 184 patients, randomized equally to two study arms. There will be one study visit during which study medication will be administered and assessments will be completed. A follow-up safety visit will occur on day 3. The primary objective of this study is to compare IM ketamine to a combination of IM midazolam and haloperidol with regards to the time required for adequate behavioral control, in minutes, in patients presenting to the ED with psychomotor agitation and violent behavior, as measured by the Richmond Agitation-Sedation Scale (RASS)., Discussion: We present a novel study to determine whether ketamine is a rapid and safe option, compared to a combination of midazolam and haloperidol for the sedation of patients presenting to the ED with psychomotor agitation and violent behavior. To our knowledge, this study is the first randomized controlled trial to compare ketamine to current standard care for this indication. We have attempted to address numerous logistical issues with the design of this study including a waiver of consent, ensuring adequate blinding of outcome assessors, patient enrolment, and data monitoring., Trial Registration: Clinicaltrials.gov, NCT03375671 . Registered on 18 December 2017.

The objective of this study was to identify predictors of sustained psychotic symptoms after methamphetamine (MA) abuse during the course of 6 months from patterns of MA and other substance use, depressive symptoms, family history of psychosis, antisocial personality disorder, and trauma history. A total of 295 individuals with MA abuse and psychotic symptoms seeking psychiatric services were assessed at baseline and then monthly on symptoms and substance use for 6 months. Trajectory analyses revealed two trajectories of the individuals with positive symptoms, with one group presenting with persistent psychotic symptoms (30% of the sample). Those with persistent psychosis were significantly older, had more severe psychotic symptoms, misused MA for more years, had more antisocial personality traits, and had more sustained depressive symptoms. The strongest predictors of belonging to the persistent psychosis group, via logistic regressions, were more severe psychotic symptoms, longer use of MA, and sustained depressive symptoms. Our results highlight the important comorbidities, especially regarding depressive symptoms and persistent psychosis, in individuals seeking psychiatric help after MA abuse. This study also highlights the importance of identifying people with persistent psychosis within MA users to facilitate rapid and effective treatment of co-occurring psychotic disorder.