Physiologically-based pharmacokinetic model to investigate the effect of pregnancy on risperidone and paliperidone pharmacokinetics: Application to a pregnant woman and her neonate.

This study aimed to determine the effects of pregnancy and ontogeny on risperidone and paliperidone pharmacokinetics by assessing their serum concentrations in two subjects and constructing a customized physiologically-based pharmacokinetic (PBPK) model. Risperidone and paliperidone serum concentrations were determined in a pregnant woman and her newborn. PBPK models for risperidone and paliperidone in adults, pediatric, and pregnant populations were developed and verified using the Simcyp simulator. These models were then applied to our two subjects, generating their "virtual twins." Effects of pregnancy on both drugs were examined using models with fixed pharmacokinetic parameters. In the neonatal PBPK simulation, 10 different models for estimating the renal function of neonates were evaluated. Risperidone was not detected in the serum of both pregnant woman and her newborn. Maternal and neonatal serum paliperidone concentrations were between 2.05-3.80 and 0.82-1.03 ng/ml, respectively. Developed PBPK models accurately predicted paliperidone's pharmacokinetics, as shown by minimal bias and acceptable precision across populations. The individualized maternal model predicted all observed paliperidone concentrations within the 90% prediction interval. Fixed-parameter simulations showed that CYP2D6 activity largely affects risperidone and paliperidone pharmacokinetics during pregnancy. The Flanders metadata equation showed the lowest absolute bias (mean error: 22.3% ± 6.0%) and the greatest precision (root mean square error: 23.8%) in predicting paliperidone plasma concentration in the neonatal population. Our constructed PBPK model can predict risperidone and paliperidone pharmacokinetics in pregnant and neonatal populations, which could help with precision dosing using the PBPK model-informed approach in special populations.

Abrupt Late-onset Psychosis as a Presentation of Coronavirus 2019 Disease (COVID-19): A Longitudinal Case Report.

INTRODUCTION: Coronavirus Disease 2019 (COVID-19) is a pandemic infection caused by the Severe Acute Respiratory Syndrome 2 Coronavirus (SARS-2-CoV). Although most prominently associated with pulmonary manifestations, COVID-19 is increasingly implicated in neuropsychiatric complications, including delirium and psychosis. There is a potential causal link between COVID-19 infection and psychotic symptoms; however, case reports to date have been incomplete, as the patients described had known psychiatric histories or other plausible medical causes for altered mental status. We present a longitudinal case of COVID-19 psychosis in a patient who underwent comprehensive diagnostic evaluation. This case is a contribution to the inchoate characterization of neuropsychiatric manifestations of COVID-19 infection. CASE REPORT: We present a case of late-onset psychosis in a middle-aged man with no psychiatric history who tested positive for COVID-19 on admission following a recently resolved upper respiratory illness. His acute presentation-characterized by delusions, hallucinations, and disorganized thought and behavior, for which he required inpatient medical admission and subsequent inpatient psychiatric hospitalization-was successfully treated. During his hospitalization, he underwent comprehensive medical and neurological workup (including neuroimaging; electroencephalography; and serum and cerebrospinal fluid testing) that was grossly unremarkable. DISCUSSION: Despite myriad potential causes of the patient's psychosis, this patient's diagnostic workup was largely unrevealing, apart from his nasopharyngeal SARS-2-CoV reverse transcriptase polymerase chain reaction assay. As such, psychosis secondary to COVID-19 infection emerged as the presumptive diagnosis.

The effect of prohibiting outside food during COVID-19 pandemic on the body weight of schizophrenic patients taking olanzapine or clozapine: a retrospective self-controlled study.

BACKGROUND: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition. METHODS: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated. RESULTS: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (ß =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found. CONCLUSIONS: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.

Brief psychotic disorder associated with quarantine and mild COVID-19.

A 30-year-old man with no significant previous or family psychiatric history became severely anxious about his health after a positive COVID-19 test. Physical symptoms of COVID-19 were mild, with no evidence of hypoxia or pneumonia, throughout his illness. He was admitted to a quarantine facility. He remained highly anxious, and 1 week later, he developed paranoid delusions and auditory hallucinations (his first psychotic episode). He was treated with lorazepam 1 mg four times a day, mirtazapine 30 mg nocte and risperidone 1 mg two times a day. His psychotic symptoms lasted 1 week. He stopped psychiatric medication after 4 weeks and had remained well when reviewed 3 months later. A Diagnostic and Statistical Manual of Mental Disorders fifth edition diagnosis of brief psychotic disorder with marked stressor (brief reactive psychosis) was made. Anxiety about his health and social isolation appeared the main aetiological factors but an inflammatory component cannot be excluded. The case highlights that first episode psychosis can be associated with mild COVID-19.