Atypical Antipsychotic Medications Research Articles

Olanzapine Versus Quetiapine: Corrected QT Changes in Critically Ill Patients.

Olanzapine and quetiapine are frequently administered atypical antipsychotic medications and their effects on the corrected QT (QTc) in the critically ill population remain understudied. The objective of this study was to compare the impact of olanzapine and quetiapine on QTc changes in critically ill patients. This was a single-center, retrospective analysis. Adult patients admitted to the intensive care unit (ICU) from January 2023 through July 2023 were included if they received ≥2 doses of either olanzapine or quetiapine within a 48-hour period and had one QTc evaluated within 48 hours of antipsychotic initiation. The major endpoint was a composite of the incidence of QTc prolongation (defined as QTc > 500 ms or QTc > 60 ms above baseline) following antipsychotic initiation. Univariable and multivariable analyses were performed to identify risk factors for QTc prolongation. There was no statistical difference in the major composite endpoint between patients in the olanzapine and quetiapine groups (8/83 [9.6%] vs 19/129 [14.7%]; P = .28). The incidence of QTc > 500 ms (7/244 [2.9%] vs 20/427 [4.7%]; P = .25) and change from baseline >60 ms (5/244 [2.0%] vs 17/427 [4.0%]; P = .26) were not statistically different between the olanzapine and quetiapine groups, respectively. There were no occurrences of Torsades de Pointes or extrapyramidal symptoms in either group. The results of this study suggest olanzapine and quetiapine may have similar impact on QTc prolongation in critically ill patients. These findings could contribute to safer prescribing practices in the ICU.

An economic model to understand the cost-effectiveness of olanzapine orally dispersible tablets (ODT) and olanzapine film coated tablets as a group compared with other oral atypical antipsychotics for treating schizophrenia in Morocco

BackgroundAntipsychotic medications are the primary treatment for schizophrenia, with olanzapine being an effective medication for schizophrenia. The economic cost for each individual with schizophrenia is high, with antipsychotic medication being a major expense. This study aims to develop an economic decision model that compares different treatment options for schizophrenia patients, including olanzapine Orally Dispersible Tablets (ODT), olanzapine [ODT + Standard Oral Tablet (SOT)], risperidone (ODT + SOT), and aripiprazole (ODT + SOT), to determine their cost-effectiveness with an objective to optimize healthcare resource allocation in Morocco.MethodsThe study used published medical literature and a clinical expert panel to develop a decision analytic model. This model was designed to capture parameters such as adherence levels, treatment discontinuation, relapse with and without hospitalization, quality-adjusted life years (QALYs), treatment-related adverse events, healthcare resource utilization, and associated costs. The main outcomes of interest included the total annual direct cost per treatment, QALYs, and incremental cost-effectiveness ratio (ICER) per 1 QALY gained. One-way and probabilistic sensitivity analyses were employed to account for parameter uncertainty.ResultsAccording to the simulation model, the ODT and ODT + SOT as a group form of olanzapine was the most effective treatment option in terms of the lowest percentages of inpatient relapse, and patients who remained stable (11% and 79% respectively) than risperidone (19% and 62% respectively) and aripiprazole ODT (26% and 50% respectively) and ODT + SOT formulation groups. Olanzapine (ODT + SOT) therapy group was cost-effective when compared to the combined group of ODT + SOT forms of risperidone [ICER: Moroccan Dirham (MAD) 103,907], and aripiprazole (ICER: MAD 65,047). Additionally, olanzapine ODT was found to be cost-effective compared to olanzapine SOT with an ICER of MAD 3921, risperidone ODT with an ICER of MAD 1,02,298, risperidone SOT with an ICER of MAD 31,088, and aripiprazole ODT or SOT formulations. All the above ICERs fall under the willingness-to-pay threshold in Morocco of MAD 250,832.40. Sensitivity analyses confirmed the reliability of the findings.ConclusionsThe model concluded that olanzapine ODT is the most cost-effective first-line treatment option for schizophrenia in Morocco when compared to other atypical antipsychotic medications in ODT and SOT formulations.

Novel long-acting treatment for schizophrenia based on paliperidone dissolving and implantable microarray patches

Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients’ adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. In vitro release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43–71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. Ex vivo delivery study showed that 1.68 ± 0.23 mg, 1.39 ± 0.07 mg, and 1.18 ± 0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag.

Risperidone Pellets, Pycnogenol®, and Glucomannan Gummy Formulation for Managing Weight Gain and ADHD in Autistic Children.

Gummy formulations are defined as gradually or slowly released solid oral dosage forms. Risperidone is an atypical antipsychotic medication used to treat schizophrenia and autism-related irritability. This study presents the development of visually appealing, patient-tailored medicated gummies that act as a novel pharmaceutical form of Risperidone for pediatrics. In this study, two gummy bases were used, one containing Glucomannan and the other containing Gelatin as a gelling agent, where these gummy bases were loaded with coated Risperidone pellets with a controlled release layer. The final products were evaluated for their pH, viscosity, content uniformity, drug content, and dissolution profile. Both formulas showed proper rheology and met content and weight uniformity standards. The release rates for F1 and F2 in the acidic media were 25% and 11%, respectively, after 2 h. At the same time, a full-release profile for Risperidone was noticed in both formulae at pH 6.8 where the release lasts for 24 h. It can be concluded that the chewable semi-solid dosages (gummies) filled with coated pellets are suitable for pediatric patients since pediatrics have drug-related problems which can be solved using high gastro-resistance coated pellets, which also shows a proper release profile for the drug.

Multimodal prediction of the need of clozapine in treatment resistant schizophrenia; a pilot study in first-episode psychosis

As many as one third of the patients diagnosed with schizophrenia do not respond to first-line antipsychotic medication. This group may benefit from the atypical antipsychotic medication clozapine, but initiation of treatment is often delayed, which may worsen prognosis. Predicting which patients do not respond to traditional antipsychotic medication at the onset of symptoms would provide fast-tracked treatment for this group of patients. We collected data from patient records of 38 first-episode psychosis patients, of whom seven did not respond to traditional antipsychotic medications. We used clinical data including medical records, voxel-based morphometry MRI data and inter-subject correlation fMRI data, obtained during movie viewing, to predict future treatment resistance. Using a neural network model, we correctly predicted future treatment resistance in six of the seven treatment resistance patients and 25 of 31 patients who did not require clozapine treatment. Prediction improved significantly when using imaging data in tandem with clinical data. The accuracy of the neural network model was significantly higher than the accuracy of a support vector machine algorithm. These results support the notion that treatment resistant schizophrenia could represent a separate entity of psychotic disorders, characterized by morphological and functional changes in the brain which could represent biomarkers detectable at early onset of symptoms.

Oral discomfort and health behavior of patients with typical vs. atypical antipsychotic drugs.

Psychiatric patients suffer from oral diseases and side effects of antipsychotic medication. In particular, the typical antipsychotic drugs may cause severe hyposalivation with subsequent oral symptoms. We therefore aimed to compare oral health behavior and oral side effects of in-hospital patients taking typical vs. atypical antipsychotic drugs with the hypothesis that the former drugs cause more oral pain than the newer drugs. This cross-sectional questionnaire and interview study investigated subjective oral symptoms and their health behavior in 170 hospitalized psychiatric patients, comparing those taking typical vs. atypical antipsychotic drugs. Cross-tabulations and chi-square tests were used for analyses. Persistent oral pain lasting throughout the day was reported by 46% in the typical, and 5% in the atypical antipsychotic group patients, respectively. In both groups, the pain was mainly in the tongue and buccal mucosa and was described as a burning sensation. A significantly higher prevalence of xerostomia was reported in the typical antipsychotic medication group (66%) compared with the atypical antipsychotic medication group (53%, p<0.01). Self-assessed dental health was assessed as poor by two-thirds of the patients of whom 69% reported toothbrushing once daily. Approximately half of them reported having had a visit to a dentist within the previous year. Of the women 28%, and of the men 17%, respectively, had received professional consultations for oral symptoms. The current results on psychiatrically hospitalized patients emphasize the need for awareness of oral discomfort and its subsequent effects on the quality of life in this challenging patient group. Focus should also be placed on a wide range of support encouraging the patients to maintain good daily oral hygiene and seek professional dental help when needed.

Assessing the impact of long-acting injectable compared to oral antipsychotic medications on readmission to a state psychiatric hospital.

People living with schizophrenia spectrum disorder (SSD) have a higher death rate which is caused, in part, by poorer adherence to treatment as compared to those with other mental illnesses. Using long-acting injectable antipsychotic (LAI) medications can improve medication adherence and reduce hospitalizations for people living with SSD but are often underutilized. As compared to oral antipsychotic medications provided to patients with SSD at discharge from a psychiatric hospitalization, being provided with an LAI antipsychotic medication may reduce subsequent rehospitalization. Specifically, patients discharged on an atypical or second-generation LAI medication are less likely to be readmitted to the hospital when compared to those discharged on a typical first-generation oral medication. Because LAI antipsychotic medications are often underutilized as treatment options, the study findings suggest that this modality may be considered for patients with SSD when being discharged from a psychiatric hospitalization. Ideally, psychiatric-mental health nurses can educate patients about indications, benefits, and risks of using atypical or second-generation LAI antipsychotic medications during hospitalization and at discharge prevent the risk for future rehospitalizations. INTRODUCTION: People living with schizophrenia spectrum disorder (SSD) have poorer medication adherence compared to those with other mental illnesses. Long-acting injectable antipsychotic (LAI) medication use is associated with greater adherence, reduced re-hospitalizations, and improved recovery outcomes when compared to oral formulations. To compare LAI antipsychotic medication use versus oral formulations on readmission to an inpatient hospital. Medical records (N = 707) from a state psychiatric hospital in the southern region of the United States were reviewed. Controlling for demographic variables, logistic regression analyses were used to examine LAI compared to oral formulations on readmission. Compared to patients discharged with oral antipsychotic medications, those with LAIs had a lower proportion of readmission rates in 6-month and 1-year periods, but not 30-day or 2-year periods. When controlling for demographic variables, those discharged with an atypical LAI had significantly lower odds of being readmitted within the 24-year period compared to those discharged on a typical oral antipsychotic. Compared to orals, LAIs do not increase and may mitigate readmissions to psychiatric hospitalization. Psychiatric-mental health nurses and other professionals may recommend LAIs when indicated for those with SSD.

Olanzapine-induced cardiomyopathy: A mimicker of obesity cardiomyopathy?

Olanzapine, an atypical antipsychotic medication, has gained prominence in the treatment of schizophrenia and related psychotic disorders due to its effectiveness and perceived safety profile. However, emerging evidence suggests a potential link between olanzapine use and adverse cardiovascular effects, including cardiomyopathy. This narrative review explores the mechanisms, clinical implications, and management strategies associated with olanzapine-induced cardiomyopathy. A comprehensive review of the literature was conducted to investigate the relationship between olanzapine and cardiomyopathy. The search included epidemiological studies, clinical case reports, and mechanistic research focusing on the pathophysiology of olanzapine-induced cardiomyopathy. The review also examined treatment strategies for managing this potential complication. Olanzapine-induced cardiomyopathy is hypothesized to be associated with metabolic disturbances and receptor antagonism. The metabolic effects of olanzapine, such as weight gain, insulin resistance, and dyslipidemia, share similarities with obesity-related cardiomyopathy. Additionally, olanzapine's antagonism of certain receptors may contribute to cardiovascular stress. The review highlighted that patients with new-onset heart failure and significant weight gain while on olanzapine should be closely monitored for signs of cardiomyopathy. Early detection and prompt withdrawal of olanzapine, along with initiation of goal-directed medical therapy, are crucial for mitigating this potentially life-threatening condition. The relationship between olanzapine and cardiomyopathy is complex and not yet fully understood. However, the potential for significant cardiovascular risk necessitates vigilance among healthcare providers. Early identification and management of olanzapine-induced cardiomyopathy can improve patient outcomes. Further research is needed to elucidate the precise mechanisms behind this adverse effect and to develop optimized treatment strategies for patients requiring antipsychotic therapy.

Clozapine-induced pyoderma gangrenosum. A case report

IntroductionClozapine is an atypical antipsychotic medication which is mainly used in cases of treatment-resistant schizophrenia. Although it has several advantages over other typical and atypical antipsychotic medication, such as fewer relapses and lowering the risk of tardive dyskinesia and suicide it also has a range of adverse effects which makes compliance an issue for many patients.Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis clinically characterized by painful pustules or nodules that rapidly evolve in ulcers with violaceous, undermined borders and raised periphery. The etiopathogenesis of the disease remains unclear, however PG is usually manifested in the setting of an underlying immune-mediated disease, more commonly inflammatory bowel disease, rheumatoid arthritis and haematological malignancies.ObjectivesNevertheless, in the literature there are scarce reports of drug-induced PG.MethodsWe present the case of a 56-year-old woman with a diagnosis of refractory schizophrenia on clozapine treatment for 4 months, who was admitted to the emergency department for a skin eruption localized on the trunk, genital area and extremities. The clinical examination revealed numerous, discrete erythematous macules, papules and plaques with central necrosis, and multiple, sharply marginated ulcers with undermined, red to purple border. Further physical examination disclosed no systemic findings and laboratory analyses and skin biopsy were performed.ResultsOn work-up, white blood cell count and C-reactive protein (CRP) were elevated, while blood and pustule cultures were negative. Histologic examination revealed dermal necrosis and inflammation, features consistent with the diagnosis of PG. The pathergy test was positive.Image:Image 2:Image 3:ConclusionsPyoderma gangrenosum is a rare autoinflammatory skin disorder of unknown etiology. The pathogenesis of the disease is not well understood, but drug-induced PG is considered to result from neutrophil dysfunction and dysregulation of the inflammatory response. Cases of drug-induced PG are rare and attributed to certain drugs. Clozapine is an antipsychotic medication for the treatment of refractory schizophrenia. It is suggested that clozapine alters plasma TNF-α levels and thus can modulate the inflammatory response. To date, a variety of adverse skin reactions (Stevens- Johnson syndrome, DRESS syndrome etc) have been previously described in the literature. However, to the best of our knowledge, this is the first case which strongly indicates the likely association between clozapine and drug-induced PG.Disclosure of InterestNone Declared

Incidence of hypercholesterolaemia and hyperglycaemia in schizophrenic patients: Atypical antipsychotic medication and clinical variables

Background: Atypical or second-generation antipsychotic drugs commonly used in the management of schizophrenia include risperidone. Risperidone is linked to the incidence of metabolic syndrome-related adverse effects. Objective: This study aims to investigate the correlation between the administration of risperidone therapy and the incidence of metabolic syndrome in outpatients diagnosed with schizophrenia. This inquiry involves an examination of relevant laboratory parameters, specifically cholesterol, blood glucose, and haemoglobin A1c (HbA1C) levels, alongside an evaluation of pertinent clinical variables that may exert an influence. Methods: This study adopted a cross-sectional approach to receiving risperidone therapy for a minimum of three months at Grhasia Mental Hospital in Yogyakarta, Indonesia. Sampling was executed using an accidental sampling technique, targeting patients who met the predefined inclusion criteria. Results: The study enrolled a total of 97 participants, comprising 58 males and 39 females. Subsequent statistical analyses failed to demonstrate any statistically significant associations between hyperglycemia and various factors, including the risperidone regimen (p = 0.574), risperidone dosage (p = 0.619), and the duration of risperidone therapy (p = 1.000). Conclusion: Risperidone has a long-term risk of causing hyperglycemia in people with schizophrenia; consequently, blood glucose and HbA1C levels must be monitored on a regular basis.

Therapeutic action of ashwagandha extract on apoptosis and cell proliferation in the heart of rat fetuses prenatally treated with clozapine

ABSTRACT An effective atypical antipsychotic medication for treating psychosis is clozapine, especially for patients who have failed to respond to other treatments. However, clozapine-induced cardiotoxicity has generated safety concerns as it may result in sudden mortality. In addition, there is relatively little information on the safety of clozapine during pregnancy. According to several earlier studies, Withania somnifera (ashwagandha) extract has a cardioprotective effect. Therefore, this study aimed to investigate the therapeutic potential of ashwagandha root extract on clozapine-induced cardiotoxicity in rat fetuses. Pregnant rats were administered clozapine (40 mg/kg bw) and/or ashwagandha extract (300 mg/kg bw.) from the sixth to fifteenth day of gestation. Clozapine-induced oxidative stress in developing hearts by decreasing superoxide dismutase and catalase activities and increasing the concentration of cardiac malondialdehyde. Moreover, there was a significant increase in the percentage of apoptotic cells and a decrease in the proliferative capacity of cardiomyocytes. Evidently, clozapine triggered severe pathological changes in fetal cardiac tissue. In conclusion, ashwagandha root extract can be used to improve the heart oxidative stress, apoptotic and proliferation rates and histopathological changes induced by clozapine in rat fetuses during gestation.

Case series and Literature review – Clozapine Induced Transient Myocarditis. Clinical characteristics and outcomes

Introduction Clozapine is a second-generation atypical antipsychotic medication used in patients with treatment-refractory schizophrenia. Its use is limited due to its associated adverse effects, including myocarditis. These adverse effects may have variable presentations, such as myocarditis transient or persistent, and a generalized inflammatory process. Thus, clinical monitoring to inform accurate diagnosis is essential to avoid unnecessary discontinuation of clozapine, leading to psychiatric decompensation.ObjectivesTo review clinical features of clozapine induced Myocarditis and accurately identify signs and symptoms attributed to be most specific for myocarditis and determine at what stage clozapine should be discontinued.Methods We conducted a literature review on PubMed, MeSH, google scholar and Mount Sinai’s Levy Library using keywords, clozapine, drug related side effects, adverse reaction, myocarditis, treatment resistant schizophrenia. Review of two cases series was done.Results A review of 15 articles that addressed the cardiac complications of clozapine was performed. This review provides a base on variable clinical characteristics and outcomes of clozapine –induced Myocarditis. It showed patients who had myocarditis ruled out, demonstrated high prevalence of systemic signs of inflammation such as fever, malaise, tachycardia and elevated c-reactive protein. However, despite clozapine maintenance in most, this systemic response subsided without any intervention. A nonspecific inflammatory response is common when initiating clozapine, this inflammatory “clozapine storm’ occurs within the first month of initiation and is not necessarily predictive of myocarditis. These patients were monitored closely. Those confirmed with clozapine- induced myocarditis using echocardiography and cardiac magnetic resonance imaging were managed with dose reduction, laboratory monitoring, vital signs check, with early initiation of beta-blockers without discontinuation of clozapine, with improvement in their laboratory results and vital signs. Those with progressive clinical signs of myocarditis required immediate cessation of clozapine.Conclusions We are proposing a critical need for a multidisciplinary team of psychiatrists, cardiologists and pharmacists collaborating to prevent premature termination of clozapine in cases of treatment-refractory schizophrenia. Our cases showed middle aged patients with treatment - refractory schizophrenia, presenting with symptoms suggestive of clozapine induced- myocarditis, few weeks after initiation. Clozapine was continued with close monitoring, as symptoms resolved. Though clozapine is associated with myocarditis, with proper knowledge on guidelines for monitoring patients, it can mitigate unnecessary discontinuation of clozapine in those patients.Disclosure of InterestNone Declared

PREVALENCE OF METABOLIC SYNDROME AMONG PATIENTS WITH SCHIZOPHRENIA FROM LONG CARE UNIT IN FORENSIC PSYCHIATRY PROGRAM: AN OBSERVATIONAL STUDY

Introduction – Metabolic syndrome is a leading health concern among schizophrenia patients treated with antipsychotics. The morbidity and mortality rates of these patients can increase when they already have cardiovascular disease and other risk factors. This study aimed to examine the prevalence of metabolic syndrome and its relationship to various clinical parameters such as blood pressure, fasting blood glucose, triglycerides, high-density lipoprotein, and waist circumference. Methods – This disease-oriented observational study was carried out in the forensic psychiatric rehabilitation ward at the Erada &amp; Mental Health Complex - Taif, Saudi Arabia. Patients admitted to the inpatient ward between 2018 and 2023 participated in the study (N = 71). The relationship between metabolic syndrome and psychotropic medications was also examined. Schizophrenia was defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria. Metabolic syndrome was assessed based on the international criteria National Cholesterol Education Program’s Adult Treatment Panel III report (ATPIII) criteria and AHA/NHLB. Results – In this study, 71 volunteer schizophrenic patients were included, and an observational study over five years was conducted. We found the total number of metabolic syndrome patients was 40 (56.34%) compared with 31 (43.66%) patients without metabolic syndrome. The majority of metabolic syndrome patients (57.50%) were aged 41 to 50. The highest number of patients suffering from metabolic syndrome are those taking atypical antipsychotic medications. Among antipsychotic medications, aripiprazole was found the maximum number of 10 (25%) followed by olanzapine 7 (17.5%). Maximum number of metabolic syndrome parameters increased fasting blood sugar 26 (65%) followed by increased body mass index 21 (52.5%). Discuss – This research can contribute to the study of the prevalence of metabolic syndrome among patients with schizophrenia. In the present study, the prevalence of metabolic syndrome was 56.34 percent in schizophrenia. There are several metabolic side effects associated with second-generation antipsychotics and if these aren't treated properly, they can lead to serious health complications, such as diabetes, dyslipidemia, and fatal heart disease. Conclusion - In our study, metabolic syndrome was most prevalent among patients between 41 - 50 years of age. Therefore, clinicians are encouraged to screen and monitor metabolic syndrome and treat cardio-metabolic risk factors for optimum long-term management. Keywords: schizophrenia, metabolic syndrome, antipsychotics.

Altered mitochondrial lymphocyte in overweight schizophrenia patients treated with atypical antipsychotics and its association with cognitive function.

Increasing evidence indicated that schizophrenia and obesity are associated with altered mitochondrial and immune function. In this study, we investigated the levels of CRP (C-reactive protein) and mitochondrial lymphocytes in chronically treated schizophrenia patients with atypical antipsychotic medications and further explored the relationship between mitochondrial lymphocyte and weight gain as well as cognitive function in these patients. We evaluated the mitochondrial lymphocyte count of 97 patients (53 overweight, 44 non-overweight) and 100 healthy controls using mitochondrial fluorescence staining and flow cytometry (NovoCyte, Agilent Technologies, US). The serum CRP was measured by high-sensitivity enzyme-linked immunosorbent assay (ELISA). Clinical symptoms and cognitive function of the patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The results showed that mitochondrial lymphocyte counts of CD3+ T, CD3+CD4+ T, and CD3+CD8+ T cells in schizophrenia patients were higher than in the control group (p < 0.05). Additionally, overweight patients had significantly higher mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells compared to schizophrenia patients with normal weight. Stratified analysis by gender revealed that there was a statistically significant difference in CD3+CD4+ mitochondrial lymphocyte count in male patients (p = 0.014) and a marginal trend toward significance in female patients (p = 0.058). Furthermore, the mitochondrial lymphocyte counts of CD3+ T and CD3+CD4+ T cells, as well as CRP levels, were positively correlated with BMI in schizophrenia patients, but the mitochondrial lymphocyte counts of CD3+CD4+ T cells were negatively correlated with the language scale in the RBANS. Our study results provide evidence for the association between altered mitochondrial T lymphocyte and weight gain as well as cognitive impairment in schizophrenia patients treated with atypical antipsychotic medications.

Molecular basis of human trace amine-associated receptor 1 activation

The human trace amine-associated receptor 1 (hTAAR1, hTA1) is a key regulator of monoaminergic neurotransmission and the actions of psychostimulants. Despite preclinical research demonstrating its tractability as a drug target, its molecular mechanisms of activation remain unclear. Moreover, poorly understood pharmacological differences between rodent and human TA1 complicate the translation of findings from preclinical disease models into novel pharmacotherapies. To elucidate hTA1’s mechanisms on the molecular scale and investigate the underpinnings of its divergent pharmacology from rodent orthologs, we herein report the structure of the human TA1 receptor in complex with a Gαs heterotrimer. Our structure reveals shared structural elements with other TAARs, as well as with its closest monoaminergic orthologue, the serotonin receptor 5-HT4R. We further find that a single mutation dramatically shifts the selectivity of hTA1 towards that of its rodent orthologues, and report on the effects of substituting residues to those found in serotonin and dopamine receptors. Strikingly, we also discover that the atypical antipsychotic medication and pan-monoaminergic antagonist asenapine potently and efficaciously activates hTA1. Together our studies provide detailed insight into hTA1 structure and function, contrast its molecular pharmacology with that of related receptors, and uncover off-target activities of monoaminergic drugs at hTA1.

Drug-induced musical hallucination.

Musical hallucination is a rare perceptual phenomenon wherein individuals hear music in the absence of external auditory stimuli. This phenomenon occurs across diverse medical conditions and can be triggered by some drugs. The underlying mechanism of drug-induced hallucination is unknown. This study explores drug-induced musical hallucination through a literature review, aiming to investigate its pathophysiology and potential treatment modalities. A literature search was conducted until January 2024 using databases PubMed, WorldCat, Google Scholar, and DOAJ, with keywords "drugs induced musical hallucination" or "drugs" combined with "musical hallucination." The search yielded 24 articles which met inclusion criteria, encompassing 27 cases. The average patient age was 58.3years, with 67.9% females. Prevalent conditions among cases included hearing impairments, psychiatric disorders, cancers, and neurodegenerative conditions. Common trigger drugs comprised antidepressants, opioids, anti-Parkinson drugs, ketamine, and voriconazole. Musical hallucination descriptions varied widely, and 6 patients reported concurrent visual hallucinations. The onset of symptoms ranged from 75min to 240days. Treatment strategies included termination of trigger drugs, dosage reduction, alteration of administration routes or formula, switching to similar drugs, or addition of antidepressants, sedatives, or atypical antipsychotic medications. Musical hallucinations completely disappeared in 24/27 (88.9%) patients but continued in 3/27 (11.1%) patients. The current study concludes that drug-induced musical hallucination may arise from altering neurotransmitter/receptor balance and intricate interactions between trigger drugs and underlying conditions.

Association Between Persistence with Oral Atypical Antipsychotic Medications and Hospital and Emergency Department Utilization in Medicaid Patients with Schizophrenia.

To examine 1-year persistence with oral atypical antipsychotics (OAAPs) for Medicaid patients with schizophrenia and assess the association between OAAP persistence and hospital and emergency department (ED) resource utilization. Using 2016-2020 multi-state Medicaid claims data, this retrospective study followed patients diagnosed with schizophrenia for 12 months after initiating OAAP therapy. Patients started on an OAAP with no evidence of antipsychotic use in the previous 6 months were included if they had a diagnosis of schizophrenia, were not dually enrolled in Medicaid and Medicare, did not switch to a long-acting injectable antipsychotic, and were continuously eligible 6 months before and 12 months after the initial OAAP prescription (index date). OAAP persistence was measured allowing for a <60-day gap. All-cause and schizophrenia-related inpatient and emergency department (ED) resource utilization during the follow-up period were compared between OAAP persistent and non-persistent groups. The study sample of 13,007 had an average age of 39.1 years and 57.0% were male. Patients were persistent with their index OAAP for 135 days on average and 73.1% had a ≥60-day gap in antipsychotic therapy post-index. While 32.8% and 28.6% of patients who did not persist with their index OAAP restarted the index OAAP or switched to a different OAAP medication later in the year, respectively, a larger proportion (38.6%) had no further OAAP prescriptions. After adjustment for demographic and clinical variables, compared to non-persistent patients, persisting with OAAPs was significantly associated with fewer all-cause and schizophrenia-related hospitalizations (Incidence Rate Ratio [IRR]=0.742, p<0.001; IRR=0.823, p<0.001; respectively) and ED visits (IRR=0.759, p<0.001; IRR=0.773, p<0.001; respectively). Non-persistence with OAAP medication is common among patients with schizophrenia and associated with negative outcomes including increased utilization of hospital and ED resources. Patient-centered interventions that improve antipsychotic persistence should be implemented to facilitate optimal outcomes in this population.

One-Year Medication Treatment Patterns, Healthcare Resource Utilization, and Expenditures for Medicaid Patients with Schizophrenia Starting Oral Atypical Antipsychotic Medication

Oral atypical antipsychotic (OAAP) medications are the most commonly prescribed treatment for the management of schizophrenia symptoms. This retrospective study, using Medicaid claims data (2016–2020), followed patients for 12 months after initiating OAAP therapy. Study outcomes included OAAP adherence, switching, augmentation, healthcare resource utilization (HRU), and expenditures. All-cause and schizophrenia-related HRU and expenditures were compared between adherent and nonadherent cohorts. Among 13,007 included patients (39.1 ± 12.8 years of age, 57.0% male, 36.1% Black, 31.8% White, 9.7% Hispanic), 25.7% were adherent to OAAPs (proportion of days covered [PDC] ≥ 0.8). During the 1-year follow-up period, Black individuals were in possession of an OAAP for an average of 166 days compared to 198 and 202 days for White and Hispanic patients, respectively. Approximately 16% of patients switched OAAP medications and 3.2% augmented therapy with an OAAP added to their index medication. Nearly 40% of patients were hospitalized during follow-up and 68.4% had emergency department (ED) visits. A greater proportion of nonadherent patients had all-cause inpatient (41.7% vs. 34.1%, p < 0.001) and ED visits (71.7% vs. 58.8%, p < 0.001) compared to adherent patients. Annual total healthcare expenditures were $21,020 per patient; $3481 higher for adherent versus nonadherent patients. Inpatient expenditures comprised 44.6% and 30.6% of total expenditures for nonadherent and adherent patients, respectively. Hospitalized patients’ total expenditures were $23,261 higher compared to those without a hospitalization. Adherence to OAAP medication is suboptimal and associated with increased utilization of costly hospital and ED resources. Efforts to improve therapies and increase medication adherence could improve clinical and economic outcomes among individuals with schizophrenia.

Functional Dyspepsia (FD) and the Use of Sulpiride (Atypical Antipsychotic) in Family Practice– A Case Report

Functional dyspepsia (FD), a commonly prevalent multifactorial disorder of gut-brain interaction (DGBI), is encountered and managed in family practice and gastroenterology clinics. The diagnosis is solely clinical based on Rome-IV criteria, excluding the organic, systemic, or metabolic causes. Management is often challenging ranging from lifestyle modifications, H-pylori eradication, H2-receptor antagonists, proton pump inhibitors, and prokinetics (1st-line) to antidepressants, and antipsychotics (2nd line) of therapy, once the patient shows no response to 1st line. In severe cases, refractory to 1st &amp; the 2nd line of treatment needs a team approach and gut-brain behavioral therapy. Herein, we present a young female patient diagnosed with FD, managed well with 2nd-line treatment (Sulpiride), an atypical antipsychotic medication, as the patient's symptoms showed no improvement with first-line treatment.

Atypical antipsychotic use does not impact weight gain for individuals with extreme anorexia nervosa: a retrospective case–control study

BackgroundThere are no U.S. Food and Drug Administration (FDA)-approved medications for the treatment of anorexia nervosa (AN). Various medication classes have been evaluated for benefits in this population, including antipsychotics. Studies focused on use of antipsychotics for assistance with weight restoration in AN produced conflicting results. While current evidence does not suggest that antipsychotic medications can be generally recommended for persons with AN, some individuals might benefit from an antipsychotic medication for anxiety, mood, and the cognitive distortions that accompany the illness. It is well-established that atypical antipsychotics can cause weight gain when taken by other psychiatric populations. This published data can understandably limit the willingness of persons with AN to trial these medications. Given the conflicting results of studies examining antipsychotic-related weight gain in AN, it is currently hypothesized that individuals with extreme anorexia nervosa, restricting type, do not experience the weight gain seen in other psychiatric populations utilizing atypical antipsychotics.MethodsTwo hundred seventy-six individuals with extreme AN were enrolled in this retrospective, case–control study between April 1, 2016 and June 30, 2022 utilizing study-specific inclusion and exclusion criteria. Clinical and demographic data, including use of atypical antipsychotics and weights, were retrospectively obtained from chart review. Variables were assessed for normality using univariate statistics. Continuous variables were described using means (M) and standard deviations (SD) or medians and interquartile ranges (IQR) based on normality. Differences in weight gain between cohorts was ascertained via independent samples t-test. P values of < 0.05 were considered statistically significant, and all analyses were completed using SAS Enterprise Guide software version 7.1 (SAS Institute, Cary, NC) and R version 4.3.1 (R Core Team, 2023).ResultsUse of antipsychotics in this population of individuals with extreme AN did not impact the rate of weight gain (M: 1.7 kg/week, SD: 0.9 and 0.8, for cases and controls respectively).ConclusionsWeight gain is often cited by individuals with AN as a feared side effect of antipsychotic medications. In this study, there was no difference in weight trends for individuals taking atypical antipsychotic medications during the refeeding process compared with individuals who were not.