Second-generation Antipsychotic Medications Research Articles

Adherence Rates and Barriers to Second-Generation Antipsychotic Medication Use in Youth with Bipolar Spectrum Disorders Who Have Overweight/Obesity.

Objective: Youth with bipolar spectrum disorders (BSD) are frequently prescribed second-generation antipsychotics (SGAs). Nonadherence to treatment often results in increased mood symptoms and diminished quality of life. We examined SGA adherence rates and adherence barriers among youth who have overweight/obesity and are diagnosed with BSD enrolled in a multisite pragmatic clinical trial. Methods: SGA adherence and adherence barriers at baseline via patient- and caregiver report was assessed. Adherence was defined as taking ≥70% of prescribed SGA doses in the past week. The weighted Kappa statistic was used to measure child-caregiver agreement about adherence rates, barriers, and caregiver assistance. Regression analyses were used to examine associations of caregiver assistance, age, sex, race, insurance status, dosing frequency, and number of concomitant medications with adherence. Barriers to adherence were analyzed separately for youth and their caregivers, using logistic regression to assess associations between informant-reported barriers and informant-reported adherence. Results: Participants included 1485 patients and/or caregivers. At baseline, 88.6% of patients self-reported as adherent; 92.0% of caregivers reported their child was adherent. Concordance between patients and caregivers was moderate (k = 0.42). Approximately, 50% of the sample reported no adherence barriers. Frequently endorsed barriers included forgetting, side effects, being embarrassed to take medications, and preferring to do something else. Concordance between informants regarding adherence barriers was weak (k = 0.05-0.36). Patients and caregivers who did not endorse adherence barriers reported higher adherence than those who endorsed barriers. Male sex and having once daily dosing of medications were associated with lower adherence. Discussion: One-week patient- and caregiver-reported adherence was high in this sample. Half of the sample reported adherence barriers. Most commonly endorsed barriers were forgetting, side effects, being embarrassed, and preferring to do something else. Caregivers and patients have unique perspectives regarding adherence barriers. Understanding and addressing treatment barriers in clinical practice may facilitate adherence.

Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Associated Weight Gain Among Children and Adolescents.

Antipsychotic-associated weight gain (AAWG) is a common adverse effect of second-generation antipsychotic (SGA) medications among children and adolescents. This study applied group-based trajectory modeling to identify latent trajectories of AAWG among children and adolescents and associated risk factors. This was a retrospective analysis of the IQVIA Ambulatory EMR-US database from 2016 to 2021. The cohort consisted of patients aged 6 to 19 years who were SGA naive and received at least 90 days of continuous SGA prescriptions. Group-based trajectory modeling was used to identify latent trajectories of AAWG development during a 24-month period since SGA initiation, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the identified AAWG trajectories. A total of 16,262 patients were included. Group-based trajectory modeling identified the following 4 distinctive AAWG trajectories: persistent severe weight gain (4.2%), persistent moderate weight gain (20.1%), minor weight change (69.6%), and gradual weight loss (6.1%). Compared with the minor weight change group, younger age (12-17 vs 5-11: odds ratio [OR], 0.634; 95% confidence interval [CI], 0.521-0.771), lower baseline body mass index z -score (OR, 0.216; 95% CI, 0.198-0.236), and receiving olanzapine as the initial SGA (olanzapine vs aripiprazole: OR, 1.686; 95% CI, 1.673-1.699) were more likely to follow severe weight gain trajectories. The area under the receiver operating characteristic curves for comparing severe weight gain versus minor weight change groups and moderate weight vs minor weight change groups in the multinomial regression model were 0.91 and 0.8, respectively. A quarter of pediatric SGA recipients experienced persistent weight gain during the SGA treatment. The risk of having persistent AAWG can be predicted using patient characteristics collected before SGA initiation and the initial SGA agent.

Risperidone Associated With Acute Pulmonary Thromboembolism: A Case Report

Antipsychotic drugs (APs) are widely used drugs for schizophrenia. For decades, these agents are frequently associated with some side-effects, including increased the risk of Venous Thromboembolism (VTE). A case of a man (53 years old) with schizophrenia was reported in this study. The man with no identified risk factor for thromboembolism, and developed Pulmonary Embolism (PE) and Deep Vein Thrombosis (DVT) after treatment with risperidone 2 years. The current case indicates that use of risperidone for long time can be associated with the risk of PTE and DVT. Risperidone is a Second-Generation Antipsychotic medication (SGA), as a mixed serotonin 5HT2 and dopamine D2 receptor antagonist possibly implicated in this adverse event. As suggested by this observation, VTE and PTE risk not just appears to new users, so they should be vigilant monitored to ensure early detection and prompt treatment of VET and PTE during medication.

SAT620 Dopamine Challenge: Treatment Of Pituitary Macroadenoma/Prolactinoma In Patient On Antipsychotic Medication

Abstract Disclosure: A. Bazhenov: None. I. Alpertunga: None. Background When hyperprolactinemia is a well-known side effect of antipsychotic medications1, the link between prolonged treatment with dopamine antagonist and the development of lactotroph adenomas is still unclear4. Treating a patient with prolactinoma and psychotic disorder may pose a challenge. Antipsychotic agents can cause increases in prolactin levels. Additionally, treatment of prolactinoma with dopamine agonists may worsen psychotic symptoms. Case presentation We present a case of 56 yo male with a PMH of bipolar disorder with psychotic features who was found to have a macroprolactinoma after 18 years of treatment with antipsychotic medications. At age 30, the patient was diagnosed with Bipolar Disorder with psychotic features. The course of the disease was complicated by numerous hospitalizations and frequent changes to the treatment plan, with different combination of second-generation antipsychotic, haloperidol and antiseizure medications. The patient’s prolactin level was 50 ng/ml at the time. 18 years after the diagnosis, the patient developed severe headaches. An MRI revealed a pituitary macroadenoma measuring 1.3 cm, and a repeat prolactin level resulted in 729 ng/ml. He was started on cabergoline 0.5 mg twice a week. As a result, the prolactin level dropped to 32 ng/ml and the macroprolactinoma size decreased to 1.1 cm. Unfortunately, the patient was lost to follow up. Once he re-established his care, he was started on Olanzapine 15 mg daily, Lamotrigine 200 mg daily and cabergoline 0.5 mg twice a week. After reinitiating cabergoline, the patient developed three maniac episodes, two of which required hospitalization. The dose of the cabergoline was decreased to avoid future maniac episodes. Neurosurgery will be consulted for possible surgery treatment. Discussion The treatment of a patient with prolactinoma and a psychotic disorder poses a particular challenge. We believe that care of these patients requires a multidisciplinary approach, and surgical treatment should be considered for those who cannot tolerate dopamine-agonist therapy. Literature 1. Bostwick JR, et al. Antipsychotic-induced hyperprolactinemia. Pharmacotherapy. 2009;29(1):64-73. 2. Lertxundi U et al. Antipsychotics and pituitary tumors. Int Clin Psychopharmacol. 2019;34(2)89. 3. Andrade EH, et al. Insights in the management of antipsychotics. Case Rep Med. 2010;2010. 4. McCarren M,et al. Follow-up study of a pharmacovigilance signal. J Clin Psychopharmacol. 2012;32(6)743. 5. Bakker IC, et al. Successful treatment of a prolactinoma on antipsychotic drug. Endocrinol Diabetes Metab Case Rep. 2016. 6. The challenges in managing prolactinomas SFEBES2009 Accessed April 11 2023. https://endocrine-abstracts.org 7. Howes OD et al. The role of dopamine in schizophrenia. Biol Psychiatry. 2017;81(1)9. 8.Bamarinejad A, et al. Schizophrenia and Macroprolactinoma: Adv Biomed Res. 2020;9(1)38. Presentation: Saturday, June 17, 2023

Adherence to Recommended Metabolic Monitoring of Children and Adolescents Taking Second-Generation Antipsychotics.

Clinical guidelines recommend periodic monitoring for adverse metabolic effects associated with second-generation antipsychotic medications. The authors sought to evaluate adherence to the guideline-recommended metabolic monitoring schedule for children and adolescents prescribed second-generation antipsychotics. The authors used a national electronic medical records database for a retrospective study of children and adolescents ages 1-17 years (N=9,620) who were prescribed second-generation antipsychotics in January 2010-December 2018. Adherence to guideline-recommended monitoring of body mass index (BMI), blood glucose, and cholesterol was categorized as full, partial, and no monitoring. Full monitoring of patients was defined as strict metabolic monitoring, following the guideline-recommended schedule. Patients who received any monitoring, but not meeting the full monitoring criteria, were considered partially monitored. Three multinomial logistic regression models were fitted for each metabolic parameter to identify predictors associated with monitoring status. BMI was the metabolic parameter with the highest adherence to guideline-recommended monitoring (full monitoring, 4.7% of patients; partial monitoring, 44.8%), followed by blood glucose (full monitoring, 6.5%; partial monitoring, 29.4%) and cholesterol (full monitoring, 0.8%; partial monitoring, 22.4%). Being Black (vs. non-Black), having a comorbid mood disorder (vs. none), receiving olanzapine as the index second-generation antipsychotic (vs. aripiprazole), and receiving an antidepressant as a concurrent medication (vs. none) were associated with a higher likelihood of receiving both full and partial monitoring of all three metabolic parameters. Both full and partial adherence to guideline-recommended monitoring of children and adolescents prescribed second-generation antipsychotics were poor. However, children and adolescents at increased metabolic risk tended to be more closely monitored.

Illuminating Hope for Mental Health: A Drug Review on Lumateperone.

This drug review provides a comprehensive analysis of a novel antipsychotic called lumateperone, marketed as Caplyta. Lumateperone gained FDA approval in 2019 for treating schizophrenia and later, in 2021, for treating bipolar depression. The review begins by delving into lumateperone's mechanism of action, which involves the partial agonism of the dopamine D2 receptor as well as its unique effects on the dopamine transporter, N-methyl-D-aspartate (NMDA) receptor, and serotonin transporter. Additionally, the study examines lumateperone's distinctive pharmacokinetics. Moreover, this review assesses lumateperone's metabolic profile and highlights its favorable outcomes regarding mean body weight, BMI, and waist circumference, surpassing those of other second-generation antipsychotic medications. The study explicitly emphasizes the efficacy and safety of lumateperone in treating schizophrenia and bipolar depression associated with bipolar I and II disorders. An extensive investigation of multiple clinical trials provides compelling evidence of lumateperone's advantages over existing antipsychotic medications. The review also acknowledges the limitations of lumateperone compared to other antipsychotics. In conclusion, this drug review underscores the importance of further research to uncover the additional limitations of lumateperone while acknowledging its promising benefits and potential for advancing treatment options.

Drug repurposing for Alzheimer's disease from 2012-2022-a 10-year literature review.

Background: Alzheimer's disease (AD) is a debilitating neurodegenerative condition with few treatment options available. Drug repurposing studies have sought to identify existing drugs that could be repositioned to treat AD; however, the effectiveness of drug repurposing for AD remains unclear. This review systematically analyzes the progress made in drug repurposing for AD throughout the last decade, summarizing the suggested drug candidates and analyzing changes in the repurposing strategies used over time. We also examine the different types of data that have been leveraged to validate suggested drug repurposing candidates for AD, which to our knowledge has not been previous investigated, although this information may be especially useful in appraising the potential of suggested drug repurposing candidates. We ultimately hope to gain insight into the suggested drugs representing the most promising repurposing candidates for AD. Methods: We queried the PubMed database for AD drug repurposing studies published between 2012 and 2022. 124 articles were reviewed. We used RxNorm to standardize drug names across the reviewed studies, map drugs to their constituent ingredients, and identify prescribable drugs. We used the Anatomical Therapeutic Chemical (ATC) Classification System to group drugs. Results: 573 unique drugs were proposed for repurposing in AD over the last 10years. These suggested repurposing candidates included drugs acting on the nervous system (17%), antineoplastic and immunomodulating agents (16%), and drugs acting on the cardiovascular system (12%). Clozapine, a second-generation antipsychotic medication, was the most frequently suggested repurposing candidate (N = 6). 61% (76/124) of the reviewed studies performed a validation, yet only 4% (5/124) used real-world data for validation. Conclusion: A large number of potential drug repurposing candidates for AD has accumulated over the last decade. However, among these drugs, no single drug has emerged as the top candidate, making it difficult to establish research priorities. Validation of drug repurposing hypotheses is inconsistently performed, and real-world data has been critically underutilized for validation. Given the urgent need for new AD therapies, the utility of real-world data in accelerating identification of high-priority candidates for AD repurposing warrants further investigation.

Metabolic monitoring of pediatric patients prescribed second-generation antipsychotic medication.

The prevalence of psychotropic medication prescription use in youth has increased over the past several years. Despite recommendations and practice parameters established by the American Diabetes Association-American Psychiatric Association (ADA-APA) outlining metabolic monitoring of patients prescribed second-generation antipsychotic (SGA) medication, monitoring adherence for the pediatric patient population remains inadequate. This project aimed to improve metabolic monitoring of pediatric patients prescribed SGAs and discharge recommendations for follow-up monitoring within a small, child, and adolescent psychiatric hospital. This project compared metabolic monitoring adherence rates pre and postimplementation of a metabolic monitoring organizational policy developed to provide procedural guidance, using ADA-APA guidelines. Participants included prescribing clinicians (physicians and psychiatric nurse practitioners). Phase 1 chart reviews found no records of fasting blood glucose, fasting lipid profile or waist circumference. Following project implementation, chart review found that fasting blood glucose and fasting lipid profile was recorded in 21 (72.4%) of the charts, and waist circumference was recorded in 18 (62.1%) of the charts for patients prescribed SGA medication. For patients discharged on an SGA, written recommendations for follow-up metabolic monitoring improved from 13% to 70% (<0.001). Implementing an organizational metabolic monitoring policy and protocol can improve clinician adherence to ADA-APA guidelines for recording in-patient monitoring of metabolic parameters and discharge recommendations for pediatric patients prescribed SGA medication.

EPH137 Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Induced Weight Gain Among Children and Adolescents

Antipsychotic-induced weight gain (AIWG) is the most common side effect associated the use of second-generation antipsychotic (SGA) medications among children and adolescents. Group-based trajectory model (GBTM) can graphically display the longitudinal weight change overtime. The objective of this study was to model the development of AIWG among children and adolescents taking SGAs.

Effect of a decoction of Lophira alata (Banks ex P. Gaertn) on the pharmacokinetics of risperidone: Study of a drug-herb interaction

Drug interactions may cause a drug to be more or less effective (synergism or antagonism), or cause unexpected effects on the body. Risperidone is a second-generation atypical antipsychotic medication while Lophira alata is a plant used traditionally to treat psychotic disorders. A large number of patients with psychosis have been reported to simultaneously use both orthodox and traditional medicines in Africa. This research was carried out to determine the effect of concomitant administration of risperidone and Lophira alata in healthy human volunteers. The first phase of the research was carried out to establish the baseline pharmacokinetic profile of risperidone 2 mg in 18 male subjects. The second phase was carried out after a 2-week washout period, where the subjects were randomly divided into three equal groups and group A received risperidone 2 mg and decoction of the herb (9.4mg/kg) concurrently, group B received risperidone 2 mg and decoction of the herb (9.4mg/kg) was administered after 1 hour and group C received a decoction of the herb (9.4mg/kg) and risperidone 2 mg was administered after 1 hour. Blood samples were collected at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours after drug administration, and plasma analyses were carried out using a developed RP-HPLC method to determine the plasma concentrations. Subsequently, Kinetica 5.0 software was used to extrapolate pharmacokinetic parameters from the plasma concentrations. Results show that there was a significant (p &lt; 0.05) increase in the rate of absorption (ka), peak plasma concentration (Cmax) and measure of drug exposed to the body (AUC0-∞) but significant (p &lt; 0.05) decrease in the time to achieve peak plasma concentration (tmax), half-life of absorption (t1/2a) and extent of drug distribution (Vd) when risperidone and Lophira alata were administered concurrently. Drug-herb interaction was observed to be more significant (p &lt; 0.05), when Lophira alata was administered concurrently with risperidone than when administered one hour before or after Lophira alata. Decoction of Lophira alata interacts with risperidone tablets when administered together, which may be attributed to alteration in the mechanism of risperidone absorption by Lophira alata.

Second-generation antipsychotic medications and metabolic disturbance in children and adolescents

BackgroundThe second-generation antipsychotics (SGAs) are a group of antipsychotic drugs, used to treat psychiatric conditions. SGAs have been shown to precipitate rapid weight gain and dyslipidemia, as well as to promote insulin resistance, leading to the emergence of type 2 diabetes and metabolic syndrome. Prescriptions of SGAs in children have increased 6- to 10-fold during the last decade. This research work designed to find correlation between duration of second-generation antipsychotics (SGA) use, in children and adolescent, and the increase in metabolic syndrome disturbance components including weight gain, hypertension, hyperlipidemia and diabetes mellitus. This is cross-sectional analytic study was carried out in Suez Canal University Hospital, Psychiatry Outpatient Clinic on Children and adolescent aged 4–17 years. It included 151 children and adolescents diagnosed by Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). They were divided into two groups, 72 patients who regular on (SGA) as treated group and 79 patients who did not receive pharmacological medication as control group.ResultsThe overall prevalence of metabolic syndrome in the current study was high 27.81% in SGA-treated children compared to 0.60% in control group. In the SGA-treated group, 22.22% had type 2 diabetes, compared with 2.53% in the control group. SGA-treated patients showed a highly significant increase in their weight, body mass index and waist circumference compared to their control group patients. The correlation of different metabolic syndrome indices and SGAs duration showed positive correlation with body mass index, fasting blood sugar, and blood lipids (low density lipoproteins and cholesterol) but negative correlation with high density lipoproteins. Blood pressure did not correlate with SGA-duration in the studied patients. Indices which showed correlation could be predictors of the metabolic syndrome developments. Although the correlation and regression model showed moderate degree of association, this is considered important issue for the young patients.ConclusionSGA treatment in children and adolescence confers a significantly increased risk for metabolic syndrome and SGA-treatment duration is important for MtS development.

Persistence and adherence to second-generation antipsychotic long-acting injectable medications for schizophrenia: A comparative study in the Australian context

To examine patient characteristics, persistence and adherence to treatment associated with use of second-generation antipsychotic long-acting injectable (SGA LAI) medications in the Australian real-world setting. Five SGA LAIs were compared using a retrospective 10% sample of prescriptions in Australian Pharmaceutical Benefits Scheme (PBS) data: paliperidone palmitate 1-monthly (PP1M), paliperidone palmitate 3-monthly (PP3M), aripiprazole monohydrate (ARI), risperidone (RLAI) and olanzapine pamoate (OLAI). Patients in the PP3M cohort were more persistent with treatment (p < 0.001). Median months of persistence: PP3M (36months); ARI (18months); PP1M (11months); OLAI (8months); RLAI (4months). Patients in the PP3M cohort were more adherent to treatment (p < 0.001): PP3M (78%); ARI (51%); PP1M (46%); OLAI (35%); RLAI (33%). Patients on PP3M treatment showed comparatively longer persistence and better adherence. Treatments for schizophrenia with longer dosing intervals may provide patients with symptomatic stability that could allow for reduced hospitalisations/relapse and increased focus on functional recovery.

RF16 | PSUN159 Poor Diet Habits, Depression and Low Physical Activity Correlate with Cardiometabolic Risk Markers in Persons with Severe Mental Illness on Second-Generation Antipsychotic Medications.

Abstract Cardiovascular morbidity and mortality are high in persons with severe mental illness. Psychotropic medications, particularly second-generation antipsychotics (SGA), and also adverse health behaviors are mediators of adverse cardiometabolic health outcomes in persons with severe mental illness. Identifying and addressing specific risk factors early and aggressively is key to improving health outcomes in these patients; yet studies addressing the above problems are limited. We therefore evaluated 39 patients with schizophrenia, schizoaffective, or bipolar disorder on SGA in a comprehensive cardiometabolic, lifestyle, and mental health screening program. Data were analyzed using SPSS version 24. As previously reported, the majority of screened patients had prediabetes (PD) or diabetes mellitus (DM), 74% per oral Glucose Tolerance Testing (oGTT), 56% per HbA1c criteria. Pulse rates, insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR, and Matsuda) were significantly different between patients classified as normal or with PD/DM, using either oGTT or HbA1c criteria. However, patients with PD/DM per HbA1c, but not oGTT criterium, also had higher waist/hip ratios (p=0.01), triglyceride (p=0.01) and hsCRP levels (p=0.04) as well as lower HDL levels (p=0.04). We then determined whether dietary habits (by UK Diabetes and Diet Questionnaire, UKDDQ), mood (by Patient Health Questionnaire, PHQ-9) and/or physical activity (average daily step count) were associated with unfavorable, and potentially modifiable cardiometabolic biomarkers (fasting, 2h-oGTT plasma glucose, serum insulin, triglycerides, HDL, LDL, HbA1c, hsCRP and adiponectin). We find that fasting plasma glucose and triglyceride levels significantly correlated with UKDDQ scores (fasting plasma glucose: r=0.34, p=0.03, fasting triglyceride levels: r=0.37, p=0.02); a trend was observed for higher insulin resistance indices (HOMA IR) being associated with higher UKDDQ scores (r=0.31, p=0.06). We also confirm a strong negative correlation of the average daily step count with hsCRP levels (r=-0.62, p&amp;lt;0.0001). PHQ-9 scores negatively correlated with adiponectin levels (r=-0.475, p&amp;lt;0.005). Altogether, in our patient population with severe mental illness on SGA, unhealthy diet habits, low physical activity, and symptoms of depression were associated with higher fasting glucose and triglycerides, higher hsCRP and lower adiponectin levels, all of which may potentially contribute to adverse cardiometabolic outcomes. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk patient population. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:06 p.m. - 1:11 p.m.

Effects of adjunctive brexpiprazole on sleep-wake and circadian parameters in youth with depressive disorders: study protocol for a clinical trial

IntroductionSleep-wake and circadian disturbance is a key feature of mood disorders with a potential causal role and particular relevance to young people. Brexpiprazole is a second-generation antipsychotic medication with demonstrated...

CE: Original Research: Cognitive Behavioral Therapy for Symptom Management in Treatment-Resistant Schizophrenia.

Treatment-resistant schizophrenia (TRS) comes with significant medical comorbidities, including heart disease, liver disease, and diabetes-all of which contribute to higher mortality rates and shortened life expectancy. Second-generation antipsychotic medications do not consistently alleviate psychotic symptoms, especially among patients with TRS. Clozapine, the gold standard of pharmacological treatment for TRS, offers only partial relief for many patients. Additional treatment approaches, which include cognitive behavioral therapy (CBT), are often necessary. The aim of this integrative review was to assess the efficacy of CBT as an adjunctive treatment for TRS in various study populations. The Johns Hopkins Nursing Evidence-Based Practice Model and Guidelines were used to guide the review. A literature search of PubMed, CINAHL, Scopus, and PsycInfo was conducted, and a total of 66 articles were identified. Strong inclusion and exclusion criteria were applied to ensure that only high-quality studies were included for analysis. Of the eight studies that met the eligibility criteria, five indicated that CBT has statistically significant efficacy in reducing positive psychotic symptoms of TRS. There was also evidence that in implementing CBT, a follow-up period of at least six months helps to sustain improvements. CBT can be a safe and effective adjunctive treatment for patients with this illness. We recommend that nurses who work in psychiatric settings, EDs, and home health or community care settings obtain training in CBT.

Long-term effects of adolescent exposure to olanzapine in C57BL/6J mice and the impact of dietary fish oil supplementation.

Second-generation antipsychotic (SGA) medications can produce abnormal weight gain and metabolic dysfunction in children, but little is known about the post-treatment consequences of adolescent SGA exposure. The objective of this study was to determine the long-term, post-treatment effects of adolescent olanzapine exposure on weight and metabolic function and whether dietary fish oil (FO) modulated any observed effects of olanzapine. Male and female mice were fed a high-fat, high-sugar (HF-HS) diet or an HF-HS diet supplemented with fish oil (HF-HS-FO) and were treated with olanzapine or vehicle for 29days beginning on postnatal day 37. In male mice, adolescent olanzapine treatment suppressed weight gain during and after treatment and improved metabolic function in adulthood; dietary fish oil reduced weight gain, increased expression of fatty acid oxidation genes, and decreased expression of genes associated with fatty acid synthesis and inflammation. In contrast, few effects were observed in female mice. The current results suggest that adolescent olanzapine exposure can produce long-term alterations in weight and metabolic function in male mice and that dietary fish oil can reduce adverse effects of lifelong consumption of an HF-HS diet. Because expected adverse effects of adolescent olanzapine treatment were not observed, the potential beneficial effects of dietary fish oil for SGA-induced weight gain and metabolic dysfunction could not be evaluated.

Characterizing aripiprazole and its ester derivatives, lauroxil and cavoxil, in interaction with dopamine D2 receptor: Molecular docking and dynamics simulations with physicochemical appraisals

Among second-generation (atypical) antipsychotic medications, aripiprazole (ARP) is of major importance as the partial agonist of the D2 receptor (D2R). Long-standing efforts in the field of a long-acting injectable formulation of aripiprazole have led to its two ester derivatives, aripiprazole lauroxil (ARP-L) and aripiprazole cavoxil (ARP-C), as prodrugs and also as atypical antipsychotics. However, information regarding the D2R binding of ARP-L and ARP-C is limited. Herein, chemoinformatics appraisal, molecular docking, and molecular dynamics (MD) simulations of ARP-L and ARP-C are presented in this study to gain insights into their physicochemical properties-activity relationship and their detailed interaction with D2R in comparison with its parent drug molecule (ARP). Both ARP derivatives, exactly like ARP itself, are not PAIN and have stronger interactions with D2R/D4R in comparison with D3R. The order of binding free energy of these antipsychotics with D2R is as follows: ARP > ARP-C ≅ ARP-L. The analysis of RMSD, RMSF, Rg, and SASA indicate that due to antipsychotic ligand binding, the stability/fluctuation, flexibility/rigidity, compactness, and solvent accessible surface area change in the intracellular regions, while intracellular residues (ICL1: 29–32, ICL2: 103–114, ICL3: 188–348) have no contribution in ΔGBinding. This perception points to the existence of allosteric communications that transforms the small changes in the orthosteric binding pocket into noticeable rearrangements in intracellular regions. Most of this orthosteric–allosteric dual effect is observed in the D2R/ARP-C complex. This work could be useful in guiding future drug discovery and development studies aimed at better-tolerated aripiprazole-based antipsychotics.

Prevalence and factors associated with overweight, obesity, and hypertension in a large clinical sample of adults with autism spectrum disorder

Adults with autism spectrum disorder (ASD) are at risk for excess bodyweight and hypertension, yet the prevalence of and clinical predictors for these health conditions remain unknown. The objective of this study was to assess the prevalence of overweight, obesity, and hypertension in a large clinical sample of adults with a confirmed diagnosis of ASD and to examine potential clinical predictors. This retrospective chart review study included adult subjects (≥ 20 years) with ASD who had been seen within the past 5 years at a multidisciplinary developmental disorders clinic. Data collected from the electronic health record included age, sex, race and ethnicity, cognitive ability, language ability, body mass index (BMI), hypertension, and use of second generation antipsychotic medications (SGAs). Of 622 adults with a confirmed diagnosis of ASD potentially eligible for the study, 483 (78%) had one or more notes in their records from the past 5 years. Those with recent notes were 23% female, 89% White, and had a mean (SD) age of 28.1 (7.1) years. Overall prevalence estimates for adults represented by this predominantly male, White, and young clinical sample were 28% (95% CI 24%, 32%) for overweight (BMI 25–29.9 kg/m2), 35% (95% CI 31%, 40%) for obesity (≥ 30 kg/m2), and 11% (95% CI 9%, 15%) for hypertension. Controlling for age and sex, intellectual disability (ID) was significantly associated with BMI (p = 0.003) but not hypertension (p = 0.69); those with moderate or more severe ID had a mean BMI that was 2.26 kg/m2 (95% CI 0.96, 3.57) lower than those with no ID. Controlling for age and sex, neither language ability, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) subtype of autism, nor past or current use of SGAs were significantly associated with BMI or hypertension. The study identified a high prevalence of overweight and obesity in adults with ASD consistent with the prevalence of these medical comorbidities in the U.S. population.

Association Between the Use of Psychotropic Medications and the Risk of COVID-19 Infection Among Long-term Inpatients With Serious Mental Illness in a New York State–wide Psychiatric Hospital System

Individuals with serious mental illness are at increased risk of severe COVID-19 infection. Several psychotropic medications have been identified as potential therapeutic agents to prevent or treat COVID-19 but have not been systematically examined in this population. To evaluate the associations between the use of psychotropic medications and the risk of COVID-19 infection among adults with serious mental illness receiving long-term inpatient psychiatric treatment. This retrospective cohort study assessed adults with serious mental illness hospitalized in a statewide psychiatric hospital system in New York between March 8 and July 1, 2020. The final date of follow-up was December 1, 2020. The study included 1958 consecutive adult inpatients with serious mental illness (affective or nonaffective psychoses) who received testing for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction or antinucleocapsid antibodies and were continuously hospitalized from March 8 until medical discharge or July 1, 2020. Psychotropic medications prescribed prior to COVID-19 testing. COVID-19 infection was the primary outcome, defined by a positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction or antibody test result. The secondary outcome was COVID-19-related death among patients with laboratory-confirmed infection. Of the 2087 adult inpatients with serious mental illness continuously hospitalized during the study period, 1958 (93.8%) underwent testing and were included in the study; 1442 (73.6%) were men, and the mean (SD) age was 51.4 (14.3) years. A total of 969 patients (49.5%) had laboratory-confirmed COVID-19 infection that occurred while they were hospitalized; of those, 38 (3.9%) died. The use of second-generation antipsychotic medications, as a class, was associated with decreased odds of infection (odds ratio [OR], 0.62; 95% CI, 0.45-0.86), whereas the use of mood stabilizers was associated with increased odds of infection (OR, 1.23; 95% CI, 1.03-1.47). In a multivariable model of individual medications, the use of paliperidone was associated with decreased odds of infection (OR, 0.59; 95% CI, 0.41-0.84), and the use of valproic acid was associated with increased odds of infection (OR, 1.39; 95% CI, 1.10-1.76). Clozapine use was associated with reduced odds of mortality in unadjusted analyses (unadjusted OR, 0.25; 95% CI, 0.10-0.62; fully adjusted OR, 0.43; 95% CI, 0.17-1.12). In this cohort study of adults hospitalized with serious mental illness, the use of second-generation antipsychotic medications was associated with decreased risk of COVID-19 infection, whereas the use of valproic acid was associated with increased risk. Further research is needed to assess the mechanisms that underlie these findings.

Chronic oral olanzapine treatment but not haloperidol decreases [3H] MK-801 binding in the rat brain Independent of dietary conditions

Haloperidol and olanzapine are first and second-generation antipsychotic (neuroleptic) medications approved to treat schizophrenia. Glutamate signaling is known to play an important role in the manifestation of schizophrenia symptoms, as phencyclidine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, replicates and exasperates these symptoms. While initial reports show that neuroleptic treatments can impact aspects of NMDAR expression, there is little attention on the interaction between neuroleptics and dietary conditions. Thus, we examined the impact of chronic haloperidol and olanzapine treatment under both normal and high-fat dietary conditions on NMDAR expression. Adult male rats were treated for 28-days with either oral vehicle, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg), and fed either a standard control diet or a high-fat diet. In-vitro receptor autoradiography binding was performed using [3H] MK-801 as a measure of NMDAR expression. Results showed that olanzapine, irrespective of the diet, significantly decreased [3H] MK-801 binding within the cingulate cortex, substantia nigra, insular cortex, piriform cortex, ectorhinal cortex and perirhinal cortex, the forelimb region of the somatosensory cortex, and all quadrants of the caudate-putamen. In contrast, haloperidol treatment did not impact [3H] MK-801 binding, and we also report no effect of diet on [3H] MK-801 binding. These data suggest that the effects seen in olanzapine treatment are not mediated by diet, nor does a 28-day chronic high-fat diet alter [3H] MK-801 binding. Furthermore, these data also importantly support that combined consumption of a high-fat diet and pharmacological treatments are not immediately detrimental to NMDARs and contribute to the expansive literature of precision medicine.