Antipsychotic Drugs: A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application.

The introduction of the first antipsychotic drug, chlorpromazine, was a milestone for psychiatry. The authors review the history, classification, indications, mechanism, efficacy, side effects, dosing, drug initiation, switching, and other practical issues and questions related to antipsychotics. Classifications such as first-generation/typical versus second-generation/atypical antipsychotics are neither valid nor useful; these agents should be described according to the Neuroscience-based Nomenclature (NbN). Antipsychotic drugs are not specific for treating schizophrenia. They reduce psychosis regardless of the underlying diagnosis, and they go beyond nonspecific sedation. All currently available antipsychotic drugs are dopamine blockers or dopamine partial agonists. In schizophrenia, effect sizes for relapse prevention are larger than for acute treatment. A major unresolved problem is the implausible increase in placebo response in antipsychotic drug trials over the decades. Differences in side effects, which can be objectively measured, such as weight gain, are less equivocal than differences in rating-scale-measured (subjective) efficacy. The criteria for choosing among antipsychotics are mainly pragmatic and include factors such as available formulations, metabolism, half-life, efficacy, and side effects in previous illness episodes. Plasma levels help to detect nonadherence, and once-daily dosing at night (which is possible with many antipsychotics) and long-acting injectable formulations are useful when adherence is a problem. Dose-response curves for both acute treatment and relapse prevention follow a hyperbolic pattern, with maximally efficacious average dosages for schizophrenia of around 5 mg/day risperidone equivalents. Computer apps facilitating the choice between drugs are available. Future drug development should include pharmacogenetics and focus on drugs for specific aspects of psychosis.

Effects of synbiotic supplementation on the components of metabolic syndrome in patients with schizophrenia: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Antipsychotic drugs may have adverse effects on the components of metabolic syndrome. Previous studies have shown that changes in the intestinal microbiome are associated with metabolic disturbances in patients with schizophrenia. The objective of this study was to determine the effects of synbiotics on the components of metabolic syndrome as primary outcomes in patients with schizophrenia. Secondary outcomes were HbA1c, insulin resistance, LDL-c, and anthropometric measurements. METHODS: In this double-blind, placebo-controlled trial, seventy patients with schizophrenia receiving antipsychotic drugs who had at least two criteria of metabolic syndrome were randomly divided into two groups to receive either two capsules of a synbiotic supplement or a placebo daily for 8 weeks. Anthropometric indices and biochemical parameters were measured at baseline and after the intervention. RESULTS: Fifty-five patients completed the study. The synbiotic supplement significantly decreased waist circumference and HbA1C compared to placebo (-2.66 ± 4.20 vs. 3.03 ± 4.50 and - 0.26 ± 0.54 vs. 0.20 ± 0.75, respectively). Although BMI did not change significantly in the synbiotic + antipsychotic group, it increased in the placebo + antipsychotic group (-0.37 ± 1.00 vs. 0.61 ± 1.09 P < 0.5). LDL-c and triglyceride (TG) levels decreased significantly in the synbiotic + antipsychotic group, but the change was not significantly different from that of the placebo + antipsychotic group. FBS, HDL-c, systolic and diastolic blood pressure, insulin resistance, and total cholesterol were not significantly different between the two groups after intervention. CONCLUSION: Synbiotic supplement may decrease waist circumference, HbA1c, LDL and TG and prevent BMI increase in patients receiving antipsychotic drugs. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT Number: IRCT20090901002394N45), Date: 26-12-2019.

Aberrant glycosylation in schizophrenia: insights into pathophysiological mechanisms and therapeutic potentials.

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ.

Interictal psychosis of epilepsy: What is the role of the neurologist?

Psychotic disorders are more frequent in people with epilepsy than the general population. They constitute one of the most serious psychiatric comorbidities which require an immediate psychopharmacologic intervention. Yet, access to psychiatrists is often limited or not available and the neurologists taking care of these patients are called-upon to start treatment with antipsychotic medication. The purpose of this manuscript is to provide clinicians with pragmatic psychopharmacologic strategies to treat interictal psychotic disorders in patients with epilepsy. We review the case of a 45 years-old man with a 35-year history of treatment-resistant focal epilepsy of bitemporal origin who developed a de-novo psychotic episode that began with insomnia, mood lability and agitation and evolved into paranoid delusions, auditory hallucinations and a thought disorder. The patient was diagnosed with an interictal psychotic episode and was treated with aripiprazole which resulted in significant improvement after reaching a 20 mg /day dose and allowed for the patient to be discharged home. In summary, interictal psychotic episodes of epilepsy are relatively frequent in patients with epilepsy and require of an early psychopharmacologic treatment to facilitate their remission or stabilization until mental health professionals can take over their long-term care. Compared to primary psychotic disorders, interictal psychotic episodes respond better and at lower doses of antipsychotic drugs.

Drugs with glutamate-based mechanisms of action in psychiatry.

Psychopharmacotherapy of major psychiatric disorders is mostly based on drugs that modulate serotonergic, dopaminergic, or noradrenergic neurotransmission, either by inhibiting their reuptake or by acting as agonists or antagonists on specific monoamine receptors. The effectiveness of this approach is limited by a significant delay in the therapeutic mechanism and self-perpetuating growth of treatment resistance with a consecutive number of ineffective trials. A growing number of studies suggest that drugs targeting glutamate receptors offer an opportunity for rapid therapeutic effect that may overcome the limitations of monoaminergic drugs. In this article, we present a review of glutamate-modulating drugs, their mechanism of action, as well as preclinical and clinical studies of their efficacy in treating mental disorders. Observations of the rapid, robust, and long-lasting effects of ketamine and ketamine encourages further research on drugs targeting glutamatergic transmission. A growing number of studies support the use of memantine and minocycline in major depressive disorder and schizophrenia. Amantadine, zinc, and Crocus sativus extracts yield the potential to ameliorate depressive symptoms in patients with affective disorders. Drugs with mechanisms of action based on glutamate constitute a promising pharmacological group in the treatment of mental disorders that do not respond to standard methods of therapy. However, further research is needed on their efficacy, safety, dosage, interactions, and side effects, to determine their optimal clinical use.

Age and sex differences in outpatient antipsychotic prescriptions for schizophrenia: a claims data study.

Most studies on antipsychotic efficacy and safety, including sex differences, focus on young schizophrenia patients. However, with an aging population, the number of older schizophrenia patients is increasing. This group faces challenges due to varying treatment responses and higher risks of adverse reactions, and guidelines often lack specific recommendations due to insufficient trials. Therefore, we investigated how age and sex influence antipsychotic prescribing practices in schizophrenia using the German Pharmacoepidemiological Research Database (GePaRD). We included patients diagnosed with schizophrenia (ICD-10 code F20.X) who had been prescribed at least one antipsychotic on an outpatient basis in at least two consecutive quarters in 2020, analyzing prescription data for 49,681 patients. Key findings include a notable preference for second-generation antipsychotics (SGAs) across all age groups, especially in younger patients, possibly due to their perceived better tolerability and efficacy. Treatment intensity with SGAs (expressed as the defined daily doses of SGAs per patient in 2020) initially increased with age, peaked among 35- to 44-year-olds, and then decreased, with the lowest treatment intensity in patients aged 65 years and older. The prescription patterns of specific SGAs and first-generation antipsychotics varied across age groups, highlighting the complexity of treatment decisions in schizophrenia management. Sex differences in prescription frequency and treatment intensity were also observed. The basic recommendation of the guideline to consider sex and age when prescribing antipsychotics therefore appears to be followed. Whether this prescribing practice is really optimal for older male and female schizophrenia patients, however, still needs to be proven in clinical trials.

Additive Inhibition of HERG Channels Expressed in Xenopus Oocytes by Antipsychotic Drugs and Citrus Juice Flavonoid Naringenin.

INTRODUCTION: Citrus juice has been shown to cause QT prolongation in electrocardiograms of healthy volunteers, and naringenin, a major flavonoid found in citrus juice, has been identified as the potent inhibitor of human ether-a-go-go-related gene (HERG) channels as the cause of QT prolongation. Inhibition of HERG channels and prolongation of QT interval by antipsychotic drugs such as haloperidol, chlorpromazine, and clozapine have also been shown. However, naringenin's effect on HERG channel function in conjunction with antipsychotic medications has not been investigated. METHODS: In the present study, we evaluated the effect of combining naringenin with antipsychotics on the function of HERG channels expressed in Xenopus oocytes. RESULTS: When 30 µm naringenin was added to antipsychotic drugs (1 µm haloperidol, 10 µm chlorpromazine, or 10 µm clozapine), significantly greater HERG inhibition was demonstrated, compared to the inhibition caused by antipsychotic drugs alone. Co-application studies also showed that the magnitudes of inhibitions caused by naringenin + antipsychotics were similar to that predicted by the allotopic interaction model, suggesting that naringenin and antipsychotics bind to the HERG channel at different sites. CONCLUSION: The results suggest that there is an additive interaction between antipsychotics and naringenin. Due to the potential for repolarization heterogeneity and a decrease in repolarization reserve, this additive HERG inhibition may increase the risk of arrhythmias.

Living systematic review and meta-analysis of plasma-concentrations of antipsychotic drugs in carriers and non-carriers of variant CYP450 genotypes: Living systematic review protocol.

Introduction: Carriers of variant alleles of genes that encode liver CYP450 and UGT enzymes may experience abnormal plasma levels of antipsychotics and, consequently, worse efficacy or tolerability. Although pharmacogenomics is a rapidly developing field, current guidelines often rely on limited, underpowered evidence. We have previously demonstrated that meta-analysis is a viable strategy for overcoming this problem. Here, we propose a project that will expand our previous work and create a living systematic review and meta-analysis of drug plasma level differences between carriers and non-carriers of variant genotype-predicted phenotypes for every pharmacokinetic drug-gene interaction relevant to commonly used antipsychotic drugs. Protocol: First, a baseline systematic review and meta-analysis will be conducted by searching for observational pharmacogenomics-pharmacokinetic studies. Data on dose-adjusted drug plasma levels will be extracted, and participants will be grouped based on their genotype for each drug-gene pair separately. Differences in plasma drug levels between different phenotypes will be compared using a random-effect ratio-of-means meta-analysis. The risk of bias will be assessed using ROBINS-I, and the certainty of evidence will be assessed using GRADE. Following the establishment of baseline results, the literature search will be re-run at least once every six months, and the baseline data will be updated and re-evaluated as new evidence is published. A freely available website will be designated to present up-to-date results and conclusions. Discussion: This systematic review will provide evidence-based results that are continuously updated with evidence as it emerges in the rapidly developing field of pharmacogenomics. These results may help psychiatrists in their decision-making, as clinicians are becoming increasingly aware of the patients' genetic data as testing becomes more widespread and cheaper. In addition, the results may serve as a scientific basis for the development of evidence-based pharmacogenomics algorithms for personalized dosing of antipsychotics to mitigate potentially harmful drug-gene interactions.

Patterns of Antipsychotic Use in Belgian Nursing Homes 2017-2022: Admission is a Decision Point.

OBJECTIVES: Chronic antipsychotic use among nursing home (NH) residents carries risks with uncertain benefits. Despite guidelines recommending restricted use, these agents remain widely prescribed. This study investigates chronic antipsychotic use in Belgian NHs. DESIGN: We examined the evolution of chronic antipsychotic use, associated NH resident profiles, impact of NH admissions, and variation among Belgian NHs in a retrospective dynamic cohort study between 2017 and 2022. SETTING AND PARTICIPANTS: Antipsychotic dispensation rates were extracted for members of the Independent Health Insurance Funds in NHs. Prescription trends and resident profiles were evaluated for around 15,000 residents yearly (n = 14,733-15,451) from 2017 to 2022 and variation was assessed among 59 NHs. The impact of NH admission was analyzed for 9647 admissions between 2020 and 2022, and variation was evaluated among 22 NHs. METHODS: For 22 antipsychotics identified at the ATC3 level, chronic use was defined as ≥80 defined daily doses (DDD) and/or ≥16 weekly dispensations per year. We analyzed changes in the 4 most frequently used antipsychotics (haloperidol, olanzapine, quetiapine, risperidone) on NH admission, with chronic use defined as ≥80 minimal prescribed doses (MPD) annually. RESULTS: The prevalence of chronic antipsychotic use among NH residents decreased from 24% in 2017 to 22.5% in 2022 (P = .002). Factors associated with higher antipsychotic use included younger age, greater dependency, and lower socioeconomic status. Upon NH admission, 30% (n = 818 of 2723) of residents discontinued treatment, while in 33% (n = 949 of 2854) treatment was initiated, predominantly with quetiapine or risperidone. This led to a small but significant increase of 1.4% after admission (P < .001). Defining chronic use as ≥80 MPD annually appeared to be more sensitive in measuring chronic antipsychotic use. CONCLUSIONS AND IMPLICATIONS: Chronic antipsychotic use remains widespread in Belgian NHs, with care transition as an important decision point. Further research should explore effects of safer (de)prescribing strategies on patient well-being.

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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.

Remission in schizophrenia spectrum disorders: A randomized trial of amisulpride, aripiprazole and olanzapine.

Schizophrenia is a serious mental disorder, and monitoring remission is a widely used measure of effectiveness of the treatment provided. It is very important to identify possible factors correlating with remission. In our substudy of BeSt InTro, a randomized controlled trial of three antipsychotic drugs, 126 patients with ICD-10 diagnoses F20-29 (F23 excluded) were randomized to one of the second-generation antipsychotic drugs amisulpride, aripiprazole or olanzapine. Remission rate was calculated at seven assessment points, with and without using the time criterion of six months included in the consensus remission criteria. Because of drop-out (n = 77), we had data for 49 patients at one-year follow-up. These data were used to calculate the one-year remission rate to 55 % (27/49), without taking into consideration the 6-month time criterion. When we applied the consensus remission criteria with the 6-month time criterion included, the one-year remission rate was calculated for 59 patients: 29 % (17/59). Antipsychotic drug naivety and low negative symptom load at baseline correlated highly with belonging to the remission group. Use of amisulpride was more probable to lead to remission than that of aripiprazole, but it was not more probable than the use of olanzapine (in per-protocol analyses). Negative symptoms showed the largest resistance to treatment. The lack of remission for the majority of the participants in this closely monitored antipsychotic drug trial is alarming and could act as a reminder that novel treatment principles are needed, especially targeted towards the negative symptoms in schizophrenia.

Antidepressant and antipsychotic prescribing in patients with type 2 diabetes in Scotland: A time-trend analysis from 2004 to 2021.

AIMS: Prescribing of antidepressant and antipsychotic drugs in general populations has increased in the United Kingdom, but prescribing trends in people with type 2 diabetes (T2D) have not previously been investigated. The aim of this study was to describe time trends in annual prevalence of antidepressant and antipsychotic drug prescribing in adult patients with T2D. METHODS: We conducted repeated annual cross-sectional analysesof a population-based diabetes registry with 99% coverage, derived from primary and secondary care data in Scotland, from 2004 to 2021. For each cross-sectional calendar year time period, we calculated the prevalence of antidepressant and antipsychotic drug prescribing, overall and by sociodemographic characteristics and drug subtype. RESULTS: The number of patients with a T2D diagnosis in Scotland increased from 161 915 in 2004 to 309 288 in 2021. Prevalence of antidepressant and antipsychotic prescribing in patients with T2D increased markedly between 2004 and 2021 (from 20.0 per 100 person-years to 33.3 per 100 person-years and from 2.8 per 100 person-years to 4.7 per 100 person-years, respectively). We observed this pattern for all drug subtypes except for first-generation antipsychotics, prescribing of which remained largely stable. The degree of increase, as well as the overall prevalence of prescribing, differed by age, sex, socioeconomic status and subtype of drug class. CONCLUSIONS: There has been a marked increase in the prevalence of antidepressant and antipsychotic prescribing in patients with T2D in Scotland. Further research should identify the reasons for this increase, including indication for use and the extent to which this reflects increases in incident prescribing rather than increased duration.

Novel Insights into Psychosis and Antipsychotic Interventions: From Managing Symptoms to Improving Outcomes.

For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling and antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there has been limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal senescence, brain volume loss, the attenuation of gamma oscillations in electroencephalograms, and the oxidation of lipids in the plasma and mitochondrial membranes. We surmise that the aberrant activation of the aryl hydrocarbon receptor by toxins derived from gut microbes or the environment drives premature cellular and neuronal senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including the impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: (1) to summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders, and (2) to discuss novel strategies for improving long-term outcomes in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor antagonists.

Effects of long-term antipsychotic medication on brain instability in first-episode schizophrenia patients: a resting-state fMRI study.

Early initiation of antipsychotic treatment plays a crucial role in the management of first-episode schizophrenia (FES) patients, significantly improving their prognosis. However, limited attention has been given to the long-term effects of antipsychotic drug therapy on FES patients. In this research, we examined the changes in abnormal brain regions among FES patients undergoing long-term treatment using a dynamic perspective. A total of 98 participants were included in the data analysis, comprising 48 FES patients, 50 healthy controls, 22 patients completed a follow-up period of more than 6 months with qualified data. We processed resting-state fMRI data to calculate coefficient of variation of fractional amplitude of low-frequency fluctuations (CVfALFF), which reflects the brain regional activity stability. Data analysis was performed at baseline and after long-term treatment. We observed that compared with HCs, patients at baseline showed an elevated CVfALFF in the supramarginal gyrus (SMG), parahippocampal gyrus (PHG), caudate, orbital part of inferior frontal gyrus (IOG), insula, and inferior frontal gyrus (IFG). After long-term treatment, the instability in SMG, PHG, caudate, IOG, insula and inferior IFG have ameliorated. Additionally, there was a positive correlation between the decrease in dfALFF in the SMG and the reduction in the SANS total score following long-term treatment. In conclusion, FES patients exhibit unstable regional activity in widespread brain regions at baseline, which can be ameliorated with long-term treatment. Moreover, the extent of amelioration in SMG instability is associated with the amelioration of negative symptoms.

Ziprasidone population pharmacokinetics and co-medication effects in Chinese patients.

Ziprasidone is widely used in the treatment of psychiatric disorders. Despite its prevalence, there is a notable lack of population pharmacokinetics (PPK) studies on ziprasidone in serum, both domestically and internationally. This study aimed to comprehensively investigate the various factors influencing the PPK characteristics of Ziprasidone, thereby providing a scientific basis for personalized treatment strategies in clinical settings. This is a retrospective study. A non-linear mixed-effects modeling method was used for data analysis, with the ziprasidone PPK model established using the Phoenix NLME 8.1 software. Model evaluation employed goodness-of-fit plots, visual predictive checks, and Bootstrap methods to ensure reliability and accuracy. To further validate the model's applicability, data from an additional 30 patients meeting the same inclusion criteria but not included in the final model were collected for external validation. Simulations were performed to explore the personalized dosage regimens. This retrospective analysis collected 547 drug concentration data points from 185 psychiatric disorder patients, along with related medical records. The data included detailed demographic information (such as age, gender, weight), dosing regimens, laboratory test results, and concomitant medication details. In the final model, Ka was fixed at 0.5 h-1 based on literature, and the population typical values for ziprasidone clearance (CL) and volume of distribution (V) were 18.74 L/h and 110.24 L, respectively. Co-administration of lorazepam and valproic acid significantly influenced the clearance of ziprasidone. Moreover, the model evaluation indicated good stability and predictive accuracy. A simple to use dosage regimen table was derived based on the results of simulations. This study successfully established and validated a PPK model for ziprasidone in Chinese patients with psychiatric disorders. The model provides a scientific reference for individualized dosing of ziprasidone and holds the potential to optimize treatment strategies, thereby enhancing therapeutic efficacy and safety.

Antipsychotic drug-induced behavioral abnormalities in common carp: The potential involvement of the gut microbiota-brain axis.

The effects of antipsychotic drugs on aquatic organisms have received widespread attention owing to their widespread use and continued release in aquatic environments. The toxicological effects of antipsychotics on aquatic organisms, particularly fish, are unexplored, and the underlying mechanisms remain unelucidated. This study aimed to use common carp to explore the effects of antipsychotics (olanzapine [OLA] and risperidone [RIS]) on behavior and the potential mechanisms driving these effects. The fish were exposed to OLA (0.1 and 10 µg/L) and RIS (0.03 and 3 µg/L) for 60 days. Behavioral tests and neurological indicators showed that exposure to antipsychotics could cause behavioral abnormalities and neurotoxicity in common carp. Further, 16 S rRNA sequencing revealed gut microbiota alteration and decreased relative abundance of some strains related to SCFA production after OLA and RIS exposure. Subsequently, a pseudo-sterile common carp model was successfully constructed, and transplantation of the gut microbiota from antipsychotic-exposed fish caused behavioral abnormalities and neurotoxicity in pseudo-sterile fish. Further, SCFA supplementation demonstrated that SCFAs ameliorated the behavioral abnormalities and neurological damage caused by antipsychotic exposure. To our knowledge, the present study is the first to investigate the effects of antipsychotics on various complex behaviors (swimming performance and social behavior) in common carp, highlighting the potential health risks associated with antipsychotic drug-induced neurotoxicity in fish. Although these results do not fully elucidate the mechanisms underlying the effects of antipsychotic drugs on fish behavior, they serve as a valuable initial investigation and form the basis for future research.

A Case of Rhabdomyolysis Induced by Antipsychotic Medication With Creatine Kinase (CK) Levels Elevated to 420,000 U/L, Resulting in Acute Kidney Injury (AKI) and Necessitating Hemodialysis.

A 45-year-old man on public welfare, who had been visiting a psychiatric hospital for schizoaffective disorder, began working as a package delivery person for the first time in the morning after receiving welfare. In the afternoon, he noticed pain in his lower back. By evening, he was unable to move, prompting an emergency call and transportation to our hospital. Blood tests revealed renal damage and elevated creatine kinase (CK) levels, resulting in hospitalization. Although he received fluid replacement after admission, he did not urinate, and his CK levels increased to 420,000 U/L, necessitating hemodialysis. Subsequently, his CK levels gradually improved over time, accompanied by increased urine output. Approximately three weeks after initiating hemodialysis, he was weaned off the treatment and discharged home 40 days after admission.

Is Antipsychotic Drug Use During Pregnancy Associated with Increased Malformation Rates and Worsening of Maternal and Infant Outcomes? A Systematic Review.

There is much debate about continuing antipsychotic medication in patients who need it when they become pregnant because benefits must be weighed against potential teratogenic and malformation effects related to antipsychotics themselves. To address this, we conducted a systematic review on the PubMed, PsycINFO and CINHAL databases and the ClinicalTrials.gov register using the following strategy: (toxicity OR teratogenicity OR malformation* OR "birth defect*" OR "congenital abnormality" OR "congenital abnormalities" OR "brain changes" OR "behavioral abnormalities" OR "behavioral abnormalities") AND antipsychotic* AND (pregnancy OR pregnant OR lactation OR delivery OR prenatal OR perinatal OR post-natal OR puerperium) on September 27, 2023. We found 38 studies to be eligible. The oldest was published in 1976, while most articles were recent. Most studies concluded that the antipsychotics, especially the second-generation antipsychotics, were devoid of teratogenic potential, while few studies were inconclusive and recommended replication. Most authoritative articles were from the Boston area, where large databases were implemented to study the malformation potential of psychiatric drugs. Other reliable databases are from Northern European registers. Overall conclusions are that antipsychotics are no more related to malformations than the disorders themselves; most studies recommend that there are no reasons to discontinue antipsychotic medications in pregnancy.

Nanogels Based on N,N-Dimethylacrylamide and ß-Cyclodextrin Triacrylate for Enhanced Solubility and Therapeutic Efficacy of Aripiprazole.

Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette's syndrome. Despite its therapeutic benefits, ARZ is characterized by a poor water solubility which provoked the development of various delivery systems in order to enhance its solubility. In the present work, a nanoscale drug delivery system based on N,N-dimethylacrylamide (DMAA) and ß-cyclodextrin triacrylate (ß-CD-Ac3) as potential aripiprazole delivery vehicles was developed. The nanogels were synthesized by free radical polymerization of DMAA in the presence of ß-CD-Ac3 as a crosslinking agent and then loaded with ARZ via host-guest inclusion complexation. The blank- and drug-loaded nanogels were evaluated using different methods. Fourier transform infrared (FTIR) spectroscopy was employed to confirm the incorporation of ß-CD moieties into the polymer network. Dynamic light scattering (DLS) was used to study the size of the developed systems. The samples exhibited a monomodal particle size distribution and a relatively narrow dispersity index. The hydrodynamic diameter (Dh) of the gels varied between 107 and 129 nm, with a tendency for slightly larger particles as the ß-CD-Ac3 fraction increased. Loading the drug into the nanocarrier resulted in slightly larger particles than the blank gels, but their size was still in the nanoscopic range (166 to 169 nm). The release profiles in PBS were studied and a sustained release pattern with no significant burst effect was observed. A cytotoxicity assessment was also conducted to demonstrate the non-toxicity and biocompatibility of the studied polymers.

Antipsychotic drugs selectively decorrelate long-range interactions in deep cortical layers.

Psychosis is characterized by a diminished ability of the brain to distinguish externally driven activity patterns from self-generated activity patterns. Antipsychotic drugs are a class of small molecules with relatively broad binding affinity for a variety of neuromodulator receptors that, in humans, can prevent or ameliorate psychosis. How these drugs influence the function of cortical circuits, and in particular their ability to distinguish between externally and self-generated activity patterns, is still largely unclear. To have experimental control over self-generated sensory feedback, we used a virtual reality environment in which the coupling between movement and visual feedback can be altered. We then used widefield calcium imaging to determine the cell type-specific functional effects of antipsychotic drugs in mouse dorsal cortex under different conditions of visuomotor coupling. By comparing cell type-specific activation patterns between locomotion onsets that were experimentally coupled to self-generated visual feedback and locomotion onsets that were not coupled, we show that deep cortical layers were differentially activated in these two conditions. We then show that the antipsychotic drug clozapine disrupted visuomotor integration at locomotion onsets also primarily in deep cortical layers. Given that one of the key components of visuomotor integration in cortex is long-range cortico-cortical connections, we tested whether the effect of clozapine was detectable in the correlation structure of activity patterns across dorsal cortex. We found that clozapine as well as two other antipsychotic drugs, aripiprazole and haloperidol, resulted in a strong reduction in correlations of layer 5 activity between cortical areas and impaired the spread of visuomotor prediction errors generated in visual cortex. Our results are consistent with the interpretation that a major functional effect of antipsychotic drugs is a selective alteration of long-range layer 5-mediated communication.