Objective: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic, has 2 initiation options: 1-day (AL NanoCrystal Dispersion [ALNCD] injection plus 30 mg oral aripiprazole on day 1 only) and 21-day (15 mg oral aripiprazole for 21 days). This post hoc analysis assessed the safety and tolerability of both initiation approaches.
Methods: We analyzed data from the first 4 weeks of 2 AL studies, one using the 1-day initiation regimen (conducted between November 2017 and March 2019) and the other using the 21-day initiation regimen (conducted between December 2011 and March 2014). Outcomes of interest during the matched 4-week period included the likelihood of adverse events (AEs), including those associated with discontinuation, rated as serious, or of special interest (injection site reactions [ISRs] and akathisia).
Results: The 1-day (n = 99) and 21-day (n = 415) initiation regimens had comparable rates of AEs (57.6% and 52.0%, respectively; most were mild), serious AEs (2.0% and 1.4%), and AEs leading to discontinuation (4.0% and 3.1%). The incidence of ISRs was 11.1% after the ALNCD injection (day 1) in the 1-day initiation regimen. ISR rates for the AL starting doses were 9.2% for the 1-day regimen (AL 1064 mg on day 8) and 3.9% for the 21-day regimen (AL 441 mg/882 mg on day 1). Rates of akathisia were 9.1% and 11.1% for the 1-day and 21-day regimens, respectively. One patient discontinued because of an ISR in the 21-day study, and 2 patients in the 21-day study discontinued because of akathisia. Mean changes from baseline in week 4 Positive and Negative Syndrome Scale total scores were -17.4 (1-day) and -19.5 (21-day).
Conclusions: Four-week safety and tolerability were similar following the initiation of AL with either the 1-day or 21-day regimen, supporting the utility of both initiation regimens. Engaging patients in discussions regarding options for initiating AL may help facilitate shared decision-making and personalization of treatment for patients with schizophrenia.
Trial Registration: ClinicalTrials.gov identifiers: NCT03345979 and NCT01469039.

Inadequate response to antipsychotic treatment is common in patients with schizophrenia. This study evaluated pimavanserin, a 5-HT 2A receptor inverse agonist/antagonist, as adjunctive treatment in patients with inadequate response. This was a 6-week, randomized, double-blind, placebo-controlled, study conducted in North America and Europe. Adult outpatients with schizophrenia and inadequate response to current antipsychotic were enrolled. Inclusion criteria included Positive and Negative Syndrome Scale (PANSS) total score ≥65 and ≤110 and retrospective antipsychotic treatment stability of 8 weeks. Pimavanserin 20 mg/day or placebo added to ongoing antipsychotic was tested in a flexible-dose paradigm with dose adjustments allowed during the first 3 weeks. The primary efficacy endpoint, PANSS total score change from baseline to week 6, was not met, although improvement was greater with pimavanserin than placebo (LS mean difference: -2.1, [95% CI: -4.5, 0.4]; P = .094). As a hierarchical testing procedure was used, additional efficacy analyses were exploratory. Clear separation from placebo was observed with pimavanserin at week 6 for the PANSS Negative Symptoms subscale (LS mean difference: -0.7, [95% CI: -1.5, 0.0]) and Marder Negative Symptom Factor score (-0.9, [-1.7, -0.1]). Analysis of European sites (81.5% of patients) revealed a difference for pimavanserin versus placebo on PANSS total score (LS mean difference: -3.1, [95% CI: -5.8, -0.4]) and Clinical Global Impressions-Severity score (-0.2, [-0.4, -0.0]). Treatment-emergent adverse events occurred in 39.9% with pimavanserin and 36.4% with placebo. Although statistical significance for the primary endpoint was not met, a trend toward improvement in negative symptoms was observed with pimavanserin, warranting further study.

Drug trials for negative symptoms in schizophrenia select patients based on the severity and stability of negative symptoms, using criteria that are not suitable for trials of acute exacerbation of schizophrenia. Here we present a method to prognostically enrich subjects having a predefined factor structure in PANSS and apply it to the measurement of negative symptoms specifically in trials of acute schizophrenia. A vector of 1335 elements based on between- and within-item variances, covariances, and differences of PANSS items was created to calculate an index of heterogeneity and to enrich for a predetermined symptom construct in PANSS. Using prerandomization PANSS scores across N = 4876 subjects in 13 trials of acute schizophrenia, we demonstrate an ability to select for a subpopulation having the greatest amount of variance explained across the 7-items of the Marder PANSS negative symptom (MPNS) construct. Network analyses on subjects enriched for MPNS construct confirm that negative symptoms were most influential in overall psychopathology, distinct from subjects without the MPNS construct. As expected for D2 antagonists, drug-placebo differences on negative symptoms with lurasidone were not specific to the subpopulation having the MPNS construct. In contrast, the novel TAAR1 agonist ulotaront demonstrated specific improvements in negative symptoms which were greatest in the MPNS subpopulation. These results demonstrate the utility of a novel prognostic enrichment strategy that can address heterogeneity in clinical trials, where patients can be selected on the basis of a greater likelihood of having the measured symptom construct (negative symptoms) related to the disorder (schizophrenia). ClinicalTrials.gov Identifiers: NCT0296938, NCT00088634, NCT00549718, NCT00615433, NCT00790192.

Ayahuasca is a plant-based psychoactive decoction, traditionally used by indigenous Amazonian peoples, which commonly contains the hallucinogen N,N-dimethyltryptamine (DMT). There is now growing interest across the Western world in psychedelics including Ayahuasca.This case describes a previously well male with no risk factors for adverse psychiatric outcomes or forensic history. Following controlled Ayahuasca use, he developed an enduring psychotic episode, during which he significantly assaulted a relative and was admitted to a forensic psychiatric unit. He was treated with the antipsychotic aripiprazole, and his psychotic symptoms abated. 18 months following his admission, recovery has been sustained.Previous case reports have described psychosis following Ayahuasca ingestion, but typically of short duration in patients with a personal or family history of psychiatric illness, or in those taking other substances. With the growing use of Ayahuasca, it is important to highlight that adverse effects may include more prolonged psychotic symptoms and the risk of psychotically mediated violence.

Clozapine is the most effective medication for the management of treatment-resistant schizophrenia and schizoaffective disorder, and its discontinuation can pose significant challenges in treatment. We present a patient with a diagnosis of schizoaffective disorder who was stable on clozapine for a decade until discontinuation due to thrombocytopenia. She experienced a relapse of her illness, presenting with psychotic and catatonic features with poor oral intake and physical health complications requiring a lengthy admission to the hospital. There was a poor response to alternative antipsychotics and a full course of electroconvulsive therapy. Intramuscular (IM) clozapine was initiated due to catatonia and refusal to accept oral medications. After receiving 10 doses of IM clozapine, she started accepting oral clozapine and made a full recovery within a few weeks. The low platelet count was persistent, and a bone marrow biopsy showed results consistent with immune thrombocytopenia being the cause of that low platelet count.

Olanzapine (OLZ) is an antipsychotic medication used to treat postpartum psychiatric symptoms. It aimed to evaluate the effects of administering OLZ to lactating rats on testicular parameters of adult Wistar rats. Mothers received 2.5, 5 or 10 mg/kg until weaning. Adult male rats showed decrease in body weight, weight of testes, epididymis, prostate, seminal gland and gonadosomatic index when higher doses of OLZ were administered. Testicular volumetric parameters, as well as the length of seminiferous tubules, were also reduced in animals treated with the highest doses of OLZ. The diameter of the seminiferous tubules and the height of the seminiferous epithelium were reduced. There was also a relevant decrease in the population of Sertoli cells and a relevant reduction in the volume of individual Leydig cells. Histopathological analysis of the testes showed lesions compatible with testicular degeneration in rats treated with the highest dose of OLZ. There was a significant reduction in plasma testosterone levels in all treatments. It is noted, therefore, that the adverse impact on the testes of the highest doses of the drug during the neonatal period persisted into adulthood, with the dose of 2.5 mg/kg of OLZ proving to be safer than the others.

OBJECTIVE: This study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders.
METHODS: Event reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine.
RESULTS: The study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder.
CONCLUSIONS: Asenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders.

BACKGROUND: Readmission, defined as any admission after discharge from the same hospital, has negative implications for health outcomes. This study aims to identify the sociodemographic and clinical factors associated with hospital readmission among psychiatric patients.
METHODS: This case-control study analyzed 202 clinical records of patients admitted to a psychiatric hospital between 2019-2021. The sample was selected using simple random sampling. Qualitative variables were presented using frequencies, percentages, and chi-square tests for association. Quantitative variables were described using central tendency measures and dispersion of data, investigated with the Kolmogorov-Smirnov test, Student\'s t-test or Wilcoxon test as appropriate. Regression analysis was conducted to determine factors linked to readmission. p < 0.05 was considered.
RESULTS: Women accounted for a higher readmission rate (59%). Patients diagnosed with schizophrenia had a higher readmission rate (63%), experienced longer transfer times to the hospital during readmissions, and had shorter hospital stays. Polypharmacy and pharmacological interactions were associated with readmission. Olanzapine treatment was identified as a risk factor for readmission (ExpB = 3.203, 95% CI 1.405-7.306, p = 0.006).
CONCLUSIONS: The findings suggest avoiding polypharmacy and medications with high side effect profiles to reduce readmissions. This study offers valuable insights for clinical decision-making from admission to discharge planning, aiming to enhance the quality of care.

BACKGROUND: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone.
METHODS: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment.
RESULTS: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05).
CONCLUSIONS: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

BACKGROUND: Cardiovascular morbidity and mortality are high in people with serious mental illness (SMI). This problem is mediated, at least in part, by metabolic side effects of second-generation antipsychotics (SGAs) and by unhealthy lifestyle behaviors. We asked whether oral glucose tolerance testing (oGTT) or hemoglobin A1c (HbA1c) is superior in identifying people with SMI at high cardiometabolic risk and whether this risk is shaped by mood, cognition, or lifestyle habits.
METHODS: We evaluated 40 patients with schizophrenia, schizoaffective, or bipolar disorder receiving SGAs by oGTT, HbA1c, comprehensive metabolic and lipid panels, and CRP. Mood was assessed using the Patient Health Questionnaire (PHQ-9), and cognition was assessed using the Saint Louis University Mental Status examination. Diet was assessed using the UK Diabetes and Diet Questionnaire (UKDDQ), and physical activity was assessed using daily step counts.
RESULTS: Most patients had prediabetes (preDM) or diabetes mellitus (DM), 72.5% by oGTT, and 52.5% by HbA1c criteria. Pulse rates and insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR; Matsuda) were significantly different between patients classified as normal or with preDM/DM, using either oGTT or HbA1c criteria. Patients with preDM/DM by HbA1c but not oGTT criteria also had higher waist/hip ratios, triglyceride, and CRP levels (p<0.05). A strong negative correlation was found between average daily step counts and CRP levels (rho = -0.62, p<0.001). Higher UKDDQ scores, or unhealthier diet habits, were associated with higher fasting plasma glucose (rho = 0.28, p = 0.08), triglyceride levels (rho = 0.31, p = 0.05), and insulin resistance (HOMA IR: rho = 0.31, p = 0.06). Higher PHQ-9 scores correlated with lower 2h-oGTT glucose levels (rho = -0.37, p<0.05).
CONCLUSIONS: OGTT screening is superior to HbA1c screening in detecting preDM and DM early. Patients identified with preDM/DM by oGTT or HbA1c screening are insulin-resistant and have higher pulse rates. Abdominal obesity, unfavorable lipid profiles, and higher CRP levels were noted in patients screened by HbA1c, but not by oGTT. Low physical activity, low depression scores, and unhealthy diet habits were associated with higher CRP and higher glucose and triglyceride levels, respectively. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk population.