Atypical Antipsychotic Drugs Research Articles

Atypical antipsychotics improve dendritic spine pathology in temporal lobe cortex neurons in a developmental rodent model of schizophrenia.

"Dendritic spine pathology" refers to alterations in density and morphology of dendritic spines, crucial in corticolimbic neurons in schizophrenia. These structural neuroplasticity changes contribute to the disease's neurobiological underpinnings, alongside alterations in other brain regions, such as temporal lobe cortices like the auditory cortex (Au1) and the entorhinal cortex (Ent), involved in sensory processing, memory, and learning. The neonatal ventral hippocampus lesion (NVHL) in rats exhibits behavioral abnormalities akin to schizophrenia symptoms and corticolimbic dendritic spine pathology, mitigated by atypical antipsychotic drugs (AADs) like risperidone (RISP) and olanzapine (OLZ). This study investigated NVHL-induced dendritic spine pathology in Au1 and Ent, evaluating RISP and OLZ effects. NVHL induced dendritic spine pathology mainly by reducing the dendritic spine density in Au1 and Ent neurons; both RISP and OLZ mitigated it, increasing dendritic spine density and mushroom spine population, the ones related with synaptic strengthening, while decreasing stubby spine population. These findings underscore the role of impaired neuroplasticity in the temporal lobe cortices in schizophrenia pathophysiology and highlight the relevance of the NVHL model for studying neuroplasticity mechanisms in the disease. They also contribute to the growing understanding of targeting structural and functional neuroplasticity for novel drugs in the pharmacotherapy of the disease.

Inhibition of HCN1 currents by norquetiapine, an active metabolite of the atypical anti-psychotic drug quetiapine.

Quetiapine is a second-generation atypical antipsychotic drug that has been commonly prescribed for the treatment of schizophrenia, major depressive disorder (depression), and other psychological disorders. Targeted inhibition of hyperpolarization-activated cyclic-nucleotide gated (HCN) channels, which generate Ih, may provide effective resistance against schizophrenia and depression. We investigated if HCN channels could contribute to the therapeutic effect of quetiapine, and its major active metabolite norquetiapine. Two-electrode voltage clamp recordings were used to assess the effects of quetiapine and its active metabolites 7-hydroxyquetiapine and norquetiapine on currents from HCN1 channels expressed in Xenopus laevis oocytes. Norquetiapine, but not quetiapine nor 7-hydroxyquetiapine, has an inhibitory effect on HCN1 channels. Norquetiapine selectively inhibited HCN1 currents by shifting the voltage-dependence of activation to more hyperpolarized potentials in a concentration-dependent manner with an IC50 of 13.9 ± 0.8μM for HCN1 and slowing channel opening, without changing the kinetics of closing. Inhibition by norquetiapine primarily occurs from in the closed state. Norquetiapine inhibition is not sensitive to the external potassium concentration, and therefore, likely does not block the pore. Norquetiapine inhibition also does not dependent on the cyclic-nucleotide binding domain. Norquetiapine also inhibited HCN4 channels with reduced efficacy than HCN1 and had no effect on HCN2 channels. Therefore, HCN channels are key targets of norquetiapine, the primary active metabolite of quetiapine. These data help to explain the therapeutic mechanisms by which quetiapine aids in the treatment of anxiety, major depressive disorder, bipolar disorder, and schizophrenia, and may represent a novel structure for future drug design of HCN inhibitors.

TRATAMENTO FARMACOLÓGICO DA ESQUIZOFRENIA: PASSADO, PRESENTE E FUTURO

Schizophrenia is a chronic and severe psychiatric disorder characterised by the manifestation of positive and negative symptoms and/or cognitive dysfunction. Treatment typically includes psychotherapy, sociotherapy and pharmacological therapy, which consists of the use of typical and atypical antipsychotic drugs, as well as dopaminergic system stabilisers. Although they do not provide a cure, these treatments can reduce the intensity and frequency of symptoms, resulting in improved quality of life and a quicker reintegration into social life. Thus, the aim of the present study was to conduct a narrative literature review on the clinical evolution of antipsychotic use throughout history, as well as to discuss potential new drugs that are still in clinical research. Studies have shown that typical antipsychotics are effective in treating positive symptoms but have no impact on negative symptoms and can even exacerbate or provoke them. Additionally, they produce highly limiting side effects, such as movement disorders. Atypical antipsychotics, on the other hand, are capable of reducing both positive and negative symptoms, and they also present fewer side effects related to the extrapyramidal motor system. However, they tend to cause metabolic disturbances. Conversely, dopaminergic system stabilisers also treat both positive and negative symptoms, with side effects that are generally better tolerated, along with a lower propensity to cause weight gain and motor disturbances. It is worth noting that many patients are unable to tolerate the various adverse reactions of the available antipsychotics. Moreover, some patients are or become refractory to their therapeutic effects. Consequently, there is currently a focus on developing new agents that have different pharmacological targets. Some of these potential new drugs have shown efficacy in refractory patients, representing a potential paradigm shift in the treatment of the disorder.

Comparative Study of Effectiveness of Haloperidol Versus Olanzapine among Patients with Schizophrenia

Aim: To compare the efficacy of oral Typical Antipsychotic drug [Haloperidol] Group A versus oral Atypical Antipsychotic drug [Olanzapine] Group B in patients who met the criteria for schizophrenia. This study includes observe and compare the positive symptoms and negative symptoms in Group A and Group B by using PSYRATS scale and negative symptom assessment tool. Study Design: Prospective comparative observational study. Place and Duration of Study: The study was carried from April 2023 – September 2023 at Psychiatric Outpatient Department in the Government Medical College and Hospital, Nagapattinam. Methodology: The study sample comprised 60 patients [N=60], The 30 subjects were in Group A and 30 subjects were in Group B who met the SCID – DSM V criteria and also include criteria 1. Age between 22 – 65 years. 2. Subject should have Minimum mental state examination [MMSE] score between 25 – 30. Paired and Unpaired t test was performed to observe statistical significance. Results: Out of 60 patients Olanzapine was associated with a mean baseline to endpoint improvement of ( -22.77) versus a Mean change of ( -14.39) in Haloperidol. Olanzapine [Group B] had higher mean difference than Haloperidol [Group A]. Conclusion: By using PSYRATS scale and Negative symptom assessment tool, Olanzapine treated group were numerically better than the Haloperidol treated group in both Negative and Positive Symptoms.

Cariprazine in Psychiatry: A Comprehensive Review of Efficacy, Safety, and Therapeutic Potential.

This article provides a comprehensive review of recent developments regarding a new atypical antipsychotic drug - cariprazine - considering the mechanism of action, efficacy, safety, and promising therapeutic option for various psychiatric disorders, including schizophrenia and bipolar disorder, therapy of addictions, and treatment in the pediatric population. Its distinct pharmacological profile, characterized by partial agonism at dopamine D2 and D3 receptors, as well as serotonin receptors - 5HT1A with a preference for the D3 receptor - sets it apart from other antipsychotics. The unique mechanism of action contributes to cariprazine's positive impact on negative symptoms in schizophrenia and an antidepressant effect. Its relatively low risk of adverse effects, such as sedation, metabolic issues, and hypotension, enhances its tolerability. In bipolar affective disorder, cariprazine exhibits effectiveness in managing both depressive and manic episodes. Ongoing research in pediatric populations suggests potential benefits in schizophrenia, bipolar I disorder, and autism spectrum disorder, but further research is necessary to establish safety and efficacy. Moreover, cariprazine shows promise in addiction therapy, particularly with coexisting psychiatric disorders. Continued research and clinical exploration may discover additional insights, broadening its use in diverse patient populations. This article aims to review the role of cariprazine, a dopamine D2/D3 and serotonin 5-HT1A receptor partial agonist, in the management of psychotic illnesses, including schizophrenia, bipolar disorder, addiction therapy, and pediatric treatment.

Neurotensin receptor-1 agonist PD 149163 modulates the lipopolysaccharide-induced behavioral disturbances in mice

BackgroundNeuroendocrine-immune homeostasis is a prerequisite for neurobehavioral performances. Dysregulation of this homeostasis manifested in behavioral dysfunctions and neurodegenerative diseases, including schizophrenia and Parkinson's disease. The present study aimed to investigate the role of PD 149163 (PD), a neurotensin agonist, in the modulation of behavioral disturbances induced by lipopolysaccharide (LPS) in mice. Thirty-six female mice, 12 weeks old, were divided into 6 groups (n = 6/group). Group I (control) mice were given intraperitoneal (i.p.) injection of saline. Group II (LPS) received LPS (1 mg/kg, i.p.) for 5 days. Group III (LPS + PD Low) and IV (LPS + PD High) have received an injection of LPS (1 mg/kg, for 5 days) and after that treated with PD 100 µg/kg and 300 µg/kg, i.p., respectively, for 21 days. Group V (PD Low) and VI (PD High) were exposed to PD 100 µg/kg and 300 µg/kg, respectively, for 21 days.ResultsIn the open-field test, the PD attenuated the behavior of LPS-exposed mice by increasing the number of squares crossed, time spent in the central square, rearing and grooming, and decreasing immobility, latency and defecation. Likewise, in the elevated plus-maze test, PD increased the number of entries on open and enclosed arms, time spent on open and enclosed arms, grooming and rearing, and reduced the head dipping and immobility in LPS-challenged mice. The PD enhanced the immobility time in the forced swimming test, and sucrose consumption in the sucrose preference test decreased after LPS exposure.ConclusionThis study suggests that PD modulates the LPS-induced anxiety and depression-like behavioral impairments and could be an alternate choice of the atypical antipsychotic drugs (AAPDs) in the future.

Associations between constipation risk and lifestyle, medication use, and affective symptoms in patients with schizophrenia: a multicenter cross-sectional study.

To investigate the association between lifestyle and atypical antipsychotic drug use in patients with schizophrenia and the risk of constipation and to assess the impact of anxiety and depressive symptoms on constipation risk. Cross-sectional convenience sampling was employed, and 271 participants aged 20-65 were enrolled. Data were collected via a structured questionnaire comprising participants' demographic data, medication information, dietary behavior assessment, and the Baecke Physical Activity Questionnaire, Beck Depression Inventory-II, and Beck Anxiety Inventory. IBM SPSS 24.0 with multivariate logistic regression was used for data analysis. We performed a subgroup analysis of anticholinergic drugs via multivariate logistic regression. In total, 180 participants had functional constipation; risk factors included female sex, anxiety symptoms, depressive symptoms, and quetiapine and aripiprazole use. Patients who drank more than 3,000cc of water daily or used risperidone were less likely to have functional constipation. Depressive and anxiety symptoms were risk factors even after adjusting for sex, use of anticholinergics and laxatives, consuming two servings of fruit, consuming three servings of vegetables, consuming more than 3,000cc of water daily, physical activity, medical comorbidity, chlorpromazine equivalent dose, and atypical antipsychotic use. Similar associations were found for two affective symptoms and functional constipation in the subgroup analysis of anticholinergic drugs. The prevalence of functional constipation in patients with schizophrenia was 66.4%. The risk factors included female sex, anticholinergics, aripiprazole, quetiapine, and depressive and anxiety symptoms. Risperidone users and those who drank 3000cc of water daily were less likely to have constipation.

A pilot study on in-utero exposure to psychotropic drugs: A comparison of pharmacological classes on neonatal and maternal outcomes

ObjectiveIn this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these. MethodWe divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs. ResultsWe used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable. ConclusionWe found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions.

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.

Olanzapine Modulate Lipid Metabolism and Adipose Tissue Accumulation via Hepatic Muscarinic M3 Receptor-Mediated Alk-Related Signaling.

Olanzapine is an atypical antipsychotic drug and a potent muscarinic M3 receptor (M3R) antagonist. Olanzapine has been reported to cause metabolic disorders, including dyslipidemia. Anaplastic lymphoma kinase (Alk), a tyrosine kinase receptor well known in the pathogenesis of cancer, has been recently identified as a key gene in the regulation of thinness via the regulation of adipose tissue lipolysis. This project aimed to investigate whether Olanzapine could modulate the hepatic Alk pathway and lipid metabolism via M3R. Female rats were treated with Olanzapine and/or Cevimeline (an M3R agonist) for 9 weeks. Lipid metabolism and hepatic Alk signaling were analyzed. Nine weeks' treatment of Olanzapine caused metabolic disturbance including increased body mass index (BMI), fat mass accumulation, and abnormal lipid metabolism. Olanzapine treatment also led to an upregulation of Chrm3, Alk, and its regulator Ptprz1, and a downregulation of Lmo4, a transcriptional repressor of Alk in the liver. Moreover, there were positive correlations between Alk and Chrm3, Alk and Ptprz1, and a negative correlation between Alk and Lmo4. However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.

Combination of UGT1A1 polymorphism and baseline plasma bilirubin levels in predicting the risk of antipsychotic-induced dyslipidemia in schizophrenia patients.

The prolonged usage of atypical antipsychotic drugs (AAPD) among individuals with schizophrenia often leads to metabolic side effects such as dyslipidemia. These effects not only limit one's selection of AAPD but also significantly reduce compliance and quality of life of patients. Recent studies suggest that bilirubin plays a crucial role in maintaining lipid homeostasis and may be a potential pre-treatment biomarker for individuals with dyslipidemia. The present study included 644 schizophrenia patients from two centers. Demographic and clinical characteristics were collected at baseline and 4 weeks after admission to investigate the correlation between metabolites, episodes, usage of AAPDs, and occurrence of dyslipidemia. Besides, we explored the combined predictive value of genotypes and baseline bilirubin for dyslipidemia by employing multiple PCR targeted capture techniques to sequence two pathways: bilirubin metabolism-related genes and lipid metabolism-related genes. Our results indicated that there existed a negative correlation between the changes in bilirubin levels and triglyceride (TG) levels in patients with schizophrenia. Among three types of bilirubin, direct bilirubin in the baseline (DBIL-bl) proved to be the most effective in predicting dyslipidemia in the ROC analysis (AUC = 0.627, p < 0.001). Furthermore, the odds ratio from multinomial logistic regression analysis showed that UGT1A1*6 was a protective factor for dyslipidemia (ß = -12.868, p < 0.001). The combination of baseline DBIL and UGT1A1*6 significantly improved the performance in predicting dyslipidemia (AUC = 0.939, p < 0.001). Schizophrenia patients with UGT1A1*6 mutation and a certain level of baseline bilirubin may be more resistant to dyslipidemia and have more selections for AAPD than other patients.

Cariprazine: An Antipsychotic Medication with High Therapeutic Potential

Introduction and purposeCariprazine is an atypical antipsychotic drug approved for the treatment of schizophrenia, as well as manic and mixed episodes associated with bipolar disorder. It functions as a dopamine multifunctional agent, a partial agonist at dopamine and serotonin receptors. Unlike the majority of antipsychotics, which primarily target positive symptoms through dopaminergic antagonism, often neglecting negative, cognitive, and affective symptoms, the unique cariprazine's pharmacological profile, particularly potent blockade of D3 dopamine receptors, suggests the potential for numerous clinical applications. The aim of this study is to present current knowledge of cariprazine, focusing particularly on its mechanism of action, potential applications, adverse effects, and pharmacokinetic properties that could impact its clinical use.Methods and materialsA review of the literature available in the PubMed database was performed using the key words: cariprazine; atypical antipsychotic drug; antipsychotic medication; schizophrenia treatment; bipolar disorder treatment; mania treatment; depression treatment, dopamine agonist.ConclusionsCariprazine demonstrates a unique pharmacological profile, offering potential benefits in managing a wide range of psychiatric disorders, including schizophrenia, bipolar disorder (mania, depression, mixed episodes), unipolar depression, and co-occurring substance use disorders. Clinical studies have shown efficacy in reducing symptoms and improving negative and cognitive function, with a favorable metabolic profile, minimal impact on cardiovascular system, and generally mild adverse effect profile. However, further research is necessary to explore its full therapeutic potential and optimize its clinical use in diverse patient populations.

Prenatal aripiprazole induces alterations of rat placenta: a histological, immunohistochemical and ultrastructural study.

Antipsychotic drugs (APDs) are used to treat many psychiatric illnesses as schizophrenia. Typical antipsychotic drugs (TAPDs) are being used; however, they have many side effects. Atypical antipsychotic drugs (AAPDs) are newer medications with known fewer side effects. Aripiprazole (ARI) is an AAPD, recommended by healthcare providers, even during pregnancy. It can cross the placental barrier and enter fetal circulation, so it might be possible that ARI can adversely impair normal placental development and growth, if it is given prenatally. ARI was applied orally to pregnant female rats in two doses (3& 6mg/kg body weight). On gestation day 20, the mothers were sacrificed, and the placentas were removed and processed for general histological and electron microscopic evaluations. Immunohistochemistry was done using anti-PCNA (proliferating cell nuclear antigen), anti-Bax (for apoptosis) and anti-vascular endothelial growth factor alpha (VEGFA). Morphological evaluation revealed degenerative changes in the placenta as dark nuclei, vacuolization, and cyst formation. Ultra-structurally, there was degeneration of cellular components including organelles and nuclei. These changes were found in different cells of the basal and labyrinth zones and were dose dependent. Immunohistochemistry revealed upregulation of Bax and VEGFA and downregulation of PCNA. Prenatal administration of the AAPD, ARI to pregnant female rats resulted in histological changes in the placenta. Additionally, there was a decrease in cellular proliferation and increase in apoptosis, and vascular impairment. This indicates placental atrophy and dysgenesis and might suggest possible teratogenic effects to ARI, which needs further evaluation.

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.

The role of Galacto-oligosaccharides (GOS) in the recovery from dysbiosis in patients on long-term atypical antipsychotic treatment

Introduction Atypical antipsychotic (AAP) drugs are the gold-standard treatment for psychotic patients but are nowadays also widely prescribed among people with other mental disorders. Notwithstanding the benefits of AAP in terms of symptom improvement, there are severe adverse effects including the metabolic syndrome. A novel hypothesis is that part of these undesirable effects of antipsychotics could be mediated by their deleterious effects on the microbiome. This may result in dysbiosis, the disruption of bacterial species of the gut microbiota. Recently, dysbiosis has been linked to poor quality of life, depression and anxiety through the gut-brain axis. Mounting evidence proposes that prebiotic consumption may be helpful in the recovery of dysbiosis, although this effect is unclear among long-term antipsychotic users.ObjectivesThe main objective of this study is to assess the potential beneficial effects of the prebiotic Galacto-oligosaccharides (GOS) in combination with 2′-fucosyllactose (2’-FL) on the gut microbiota, by showing a relative increase in Bifidobacteria in fecal samples following intervention. The secondary objective is to assess the effects of GOS on mental wellbeing, sleep, and metabolic parameters. We hypothesize that GOS+2’FL supplementation will improve gut health, mental wellbeing, sleep, and metabolic parameters. Data will be collected 4 weeks prior to the start of the intervention during an observation only phase [t0], at baseline [t1], and after 2 [t2] and 6 [t3] weeks of GOS+2’FL intake. A follow-up will take place at week 10, 4 weeks after the intervention [t4]. Other outcomes that are assessed include the FiberScreen tool, the form of human faeces (Bristol Stool Chart), side effects and the defined daily dosis (DDD) of antipsychotic medication.MethodsThe study is a single-arm pilot study (non-randomized and non-blinded). We aim to include 30 psychiatric patients on long-term atypical antipsychotic use, irrespective of their specific psychiatric disorder, with a BMI &gt; 25 kg/m2. Following a run-in period of 4 weeks (no intervention but all other aspects of the study), the participants will consume GOSplus (7.0 g BiotisTMGOS + 0.7 g 2’-FL) daily during the first consumption moment of the day (preferably in the morning) for 42 days. The GOSplus powder has a slightly sweet flavour. The primary endpoint is the change in Bifidobacteria in fecal samples from week 0 to week 6.ResultsThe study started recruiting participants in October 2023.ConclusionsConclusions are expected by the end of 2024.Disclosure of InterestNone Declared

Elevated liver transaminases among patients with psychiatric disorders.

Hepatocyte injury is assessed by serum aspartate transaminase and alanine transaminase estimation. In psychiatric populations, antipsychotic drugs (AD) are culprit in hepatic dysfunction. To assess transaminitis among psychiatric patients treated by AD. This cross-sectional study was conducted in Zagazig University Hospitals in Egypt, from December 2022 to February 2023. A total of 135 adult patients aged ≥ 18 years, were diagnosed with psychiatric disorders after exclusion of patients receiving any hepatotoxic drugs, viral hepatitis, having chronic liver or kidney diseases, diabetes mellitus, mental retardation, and pregnant females. Among the 135 patients, 104 (77.0%) were males. Their age was 32 ± 9, The most popular used class of AD was atypical AD 84 (62.2%). The overall incidence of transaminitis among patients receiving AD was 23/135 (17.04%) of patients; 13 (56.5%) were on atypical AD compared to 10 (43.5%) patients receiving combined AD, without any statistically significant difference. The use of AD in patients with psychiatric disorders is potentially safe with minimal transaminitis (<one-fold elevation). However, baseline and regular monitoring of serum aminotransferase is recommended during treatment.

Association of pneumonia admission with polypharmacy and drug use in community-dwelling older people.

The purpose of the present study was to clarify the association of pneumonia admission with polypharmacy and specific drug use in community-dwelling older people. Using health insurance and long-term care insurance data from Kure city in Japan, we retrospectively collected data for older community-dwelling people (aged ≥65 years) from April 2017 to March 2019. The outcome was pneumonia admission. We carried out multivariate logistic regression analysis to identify the association of pneumonia admission with polypharmacy (≥5 drugs), the use of psychotropic drugs or anticholinergics with adjustment for patient backgrounds, such as comorbidity, and the daily life independence level for the older people with disability. Of 59 040 older people, 4017 (6.8%) participants were admitted for pneumonia in 2 years. The ratio of polypharmacy, and the use of psychotropic drugs and anticholinergics in the admission group were significantly higher than the non-admission group. Multivariate logistic regression analysis showed that polypharmacy (odds ratio 1.29, 95% confidence interval 1.18-1.41), and the use of conventional antipsychotic drugs (odds ratio 1.39, 95% confidence interval 1.02-1.90), atypical antipsychotic drugs (odds ratio 1.67, 95% confidence interval 1.37-2.05) and anticholinergics (odds ratio 1.22, 95% confidence interval 1.13-1.33) were significantly associated with pneumonia admission. The present results suggest that polypharmacy, and the use of psychotropic drugs and anticholinergics are risk factors for pneumonia admission. Geriatr Gerontol Int 2024; 24: 404-409.

Revealing receptor-ligand interactions of atypical antipsychotic drugs and screening anti-schizophrenia ingredients in Magnolia officinalis based on 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models

Schizophrenia is a serious mental illness with unknown etiology, and shows increasing incidence and high lifetime prevalence rate. The main receptors related to the disease are DRD2 and 5-HTR2A. Thus, a comprehensive understanding of the interaction mode between antipsychotic drugs with relevant receptors is very important for developing more effective drugs. 5-HTR2A-SNAP-Tag/CMC and DRD2-SNAP-Tag/CMC models constructed in this work provided a new method for studying the interaction between atypical antipsychotics and the two receptors. The results of comparative experiments showed that the new models not only met the high selectivity and specificity of the screening requirements but were also more stable and long-lasting than the traditional CMC model. Binding assays showed that the effects of three atypical antipsychotics (including clozapine, olanzapine, and quetiapine) on 5-HTR2A were stronger than their effects on DRD2. Additionally, two potentially active components, magnolol and honokiol, were screened in Magnolia officinalis methanol extract using the 5-HTR2A-SNAP-Tag/CMCHPLC-MS system. Nonlinear chromatographic analysis and molecular docking were conducted to study the interactions between screened compounds and the two receptors. The binding constants (KA) of magnolol and honokiol with 5-HTR2A were 17,854 ± 1,117 M–1 and 38,858 ± 4,964 M–1, respectively, and KA values with DRD2 were 4,872 ± 1,618 M–1 and 20,692 ± 10,267 M–1, respectively. We concluded that the established models are reliable for studying receptor-ligand interactions and screening antagonists of schizophrenia.

Clozapine Induces Neuronal Activation in the Medial Prefrontal Cortex in a Projection Target-Biased Manner.

The medial prefrontal cortex (mPFC) is associated with various behavioral controls via diverse projections to cortical and subcortical areas of the brain. Dysfunctions and modulations of this circuitry are related to the pathophysiology of schizophrenia and its pharmacotherapy, respectively. Clozapine is an atypical antipsychotic drug used for treatment-resistant schizophrenia and is known to modulate neuronal activity in the mPFC. However, it remains unclear which prefrontal cortical projections are activated by clozapine among the various projection targets. To identify the anatomical characteristics of neurons activated by clozapine at the mesoscale level, we investigated the brain-wide projection patterns of neurons with clozapine-induced c-Fos expression in the mPFC. Using a whole-brain imaging and virus-mediated genetic tagging of activated neurons, we found that clozapine-responsive neurons in the mPFC had a wide range of projections to the mesolimbic, amygdala and thalamic areas, especially the mediodorsal thalamus. These results may provide key insights into the neuronal basis of the therapeutic action of clozapine.

The Implications of Cytochrome P450 2D6/CYP2D6 Polymorphism in the Therapeutic Response of Atypical Antipsychotics in Adolescents with Psychosis-A Prospective Study.

The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.