BACKGROUND: In patients with schizophrenia, Diankuang Mengxing Decoction with antipsychotics is one of the treatments for it. However, little information is available regarding the difference between the therapeutic effect of Diankuang Mengxing Decoction with antipsychotics and other treatments. Systematic evaluation is conducted to assess the efficacy and safety of Diankuang Mengxing Decoction and other antipsychotics, which are used to treat schizophrenia.
METHODS: We performed a systematic review (PROSPERO ID: CRD42023414603). This entailed a computerized search of several research databases from their respective dates of establishment until April 11, 2023, which collected clinical randomized controlled trials of Diankuang Mengxing Decoction combined with antipsychotics. The databases that contributed to this study were PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. Each publication was screened according to defined inclusion and exclusion criteria, and appropriate literature was extracted and evaluated for quality, for which meta-analysis was performed using RevMan 5.4.
RESULTS: A literature review of 456 publications resulted in the inclusion of 18 randomized controlled trials with data collected from a total of 1636 patients. Meta-analytical results showed combination with risperidone, olanzapine, chlorpromazine, clozapine, ziprasidone, or aripiprazole increased the overall effectiveness of Diankuang Mengxing Decoction when treating schizophrenia (P < . 00001), among whom olanzapine demonstrated the greatest enhancement (Z = 3.65, odds ratio = 4.26, 95% CI: 1.96-9.28, P = .0003). The 4-week/30-day treatment (P = .0003) and a dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were more effective. Also, there were widespread reductions to the Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, general psychopathology scores (P < .05 for all), as well as the incidence of adverse effects (Z = 2.79, odds ratio = 0.34, 95% CI: 0.16-0.73, P = .005) in patients with schizophrenia.
CONCLUSIONS: The combination of Diankuang Mengxing Decoction with different antipsychotics can improve the overall prognosis of patients with schizophrenia; Diankuang Mengxing Decoction combined olanzapine, a dosage of 400 mL/d and a duration of 4 weeks/30 days being the best in this regard, by alleviating the symptoms and diminishing the disorder\'s adverse effects. To build on this work, more large-sample, multi-center, and high-quality clinical studies in the future would help to further validate our findings.

The complexity of brain activity reflects its ability to process information, adapt to environmental changes, and transition between states. However, it remains unclear how schizophrenia (SZ) affects brain activity complexity, particularly its dynamic changes. This study aimed to investigate the abnormal patterns of brain activity complexity in SZ, their relationship with cognitive deficits, and the impact of antipsychotic medication. Forty-four drug-naive first-episode (DNFE) SZ patients and thirty demographically matched healthy controls (HC) were included. Functional MRI-based sliding window analysis was utilized for the first time to calculate weighted permutation entropy to characterize complex patterns of brain activity in SZ patients before and after 12 weeks of risperidone treatment. Results revealed reduced complexity in the caudate, putamen, and pallidum at baseline in SZ patients compared to HC, with reduced complexity in the left caudate positively correlated with Continuous Performance Test (CPT) and Category Fluency Test scores. After treatment, the complexity of the left caudate increased. Regions with abnormal complexity showed decreased functional connectivity, with complexity positively correlated with connectivity strength. We observed that the dynamic complexity of the brain exhibited the characteristic of spontaneous, recurring \"complexity drop\", potentially reflecting transient state transitions in the resting brain. Compared to HC, patients exhibited reduced scope, intensity, and duration of complexity drop, all of which improved after treatment. Reduced duration was negatively correlated with CPT scores and positively with clinical symptoms. The results suggest that abnormalities in brain activity complexity and its dynamic changes may underlie cognitive deficits and clinical symptoms in SZ patients. Antipsychotic treatment partially restores these abnormalities, highlighting their potential as indicators of treatment efficacy and biomarkers for personalized therapy.

BACKGROUND: Recent studies have shown that liver enzyme abnormalities were not only seen with typical antipsychotics (APs) but also with atypical antipsychotics (AAPs). During the last 20 years, the hepatotoxicity of various antipsychotics received much attention. However, systematic evaluations of hepatotoxicity associated with APs are limited.
METHODS: All drug related hepatic disorders cases were retrieved from the FDA Adverse Event Reporting System (FAERS) database using standardized MedDRA queries (SMQ) from the first quarter of 2017 to the first quarter of 2022. Patient characteristics and prognosis were assessed. In this study, a case/non-case approach was used to calculate reporting odds ratio (RORs) and 95% confidence intervals (CIs). We calculated the drug-induced liver injury (DILI) RORs for each AAPs.
RESULTS: A total of 408 DILI cases were attributed to AAPs during the study period. 18.6% of these were designated as serious adverse event (SAE), which include death (19.74%), hospitalization (68.42%), disability (2.63%), and life-threatening (9.21%) outcomes. The RORs values in descending order were: quetiapine (ROR = 0.782), clozapine (ROR = 0.665), aripiprazole (ROR = 0.507), amisulpride (ROR = 0.308), paliperidone (ROR = 0.212), risperidone (ROR = 0.198), ziprasidone (0.131).
CONCLUSIONS: The result found in our study was that all AAPs didn\'t have a significant correlation with increased hepatotoxicity. Future analysis of the FAERS database in conjunction with other data sources will be essential for continuous monitoring of DILI.

BACKGROUND: Schizophrenia is a pervasive and severe mental disorder characterized by significant disability and high rates of recurrence. The persistently high rates of readmission after discharge present a serious challenge and source of stress in treating this population. Early identification of this risk is critical for implementing targeted interventions. The present study aimed to develop an easy-to-use predictive instrument for identifying the risk of readmission within 1-year post-discharge among schizophrenia patients in China.
METHODS: A prediction model, based on static factors, was developed using data from 247 schizophrenia inpatients admitted to the Mental Health Center in Wuxi, China, from July 1 to December 31, 2020. For internal validation, an additional 106 patients were included. Multivariate Cox regression was applied to identify independent predictors and to create a nomogram for predicting the likelihood of readmission within 1-year post-discharge. The model\'s performance in terms of discrimination and calibration was evaluated using bootstrapping with 1000 resamples.
RESULTS: Multivariate cox regression demonstrated that involuntary admission (adjusted hazard ratio [aHR] 4.35, 95% confidence interval [CI] 2.13-8.86), repeat admissions (aHR 3.49, 95% CI 2.08-5.85), the prescription of antipsychotic polypharmacy (aHR 2.16, 95% CI 1.34-3.48), and a course of disease ≥ 20 years (aHR 1.80, 95% CI 1.04-3.12) were independent predictors for the readmission of schizophrenia patients within 1-year post-discharge. The area under the curve (AUC) and concordance index (C-index) of the nomogram constructed from these four factors were 0.820 and 0.780 in the training set, and 0.846 and 0.796 for the validation set, respectively. Furthermore, the calibration curves of the nomogram for both the training and validation sets closely approximated the ideal diagonal line. Additionally, decision curve analyses (DCAs) demonstrated a significantly better net benefit with this model.
CONCLUSIONS: A nomogram, developed using pre-discharge static factors, was designed to predict the likelihood of readmission within 1-year post-discharge for patients with schizophrenia. This tool may offer clinicians an accurate and effective way for the timely prediction and early management of psychiatric readmissions.

Disrupted connectivity in the default mode network (DMN) during resting-state functional MRI (rs-fMRI) is well-documented in schizophrenia (SCZ). The amygdala, a key component in the neurobiology of SCZ, comprises distinct subregions that may exert varying effects on the disorder. This study aimed to investigate variations in functional connectivity (FC) between distinct amygdala subregions and the DMN in SCZ individuals and explore the effects of treatment on these connections. Fifty-six SCZ patients and 51 healthy controls underwent FC analysis and questionnaire surveys during resting state. The amygdala was selected as the region of interest (ROI) and subdivided into four parts. Changes in FC were examined, and correlations between questionnaire scores and brain activity were explored. Pre-treatment, SCZ patients exhibited reduced FC between the amygdala and DMN compared to HCs. After treatment, significant differences persisted in the right medial amygdala, while other regions did not differ significantly from controls. In addition, PANSS scores positively correlated with FC between the Right Medial Amygdala and the left SMFC (r = .347, p = .009), while RBANS5A scores showed a positive correlation with FC between the Left Lateral Amygdala and the right MTG (rho = -.347, p = .009). The rsFC between the amygdala and the DMN plays a crucial role in the treatment mechanisms of SCZ. This could provide a promising predictive indicator for understanding the neural mechanisms behind treatment and symptomatic improvement.

OBJECTIVE: This study aims to comprehensively assess the safety of Asenapine by conducting an comprehensive statistical analysis of adverse event reports in the FAERS database, with a particular focus on potential adverse reactions related to its use in the treatment of psychiatric disorders.
METHODS: Event reports from the first quarter of 2009 to the third quarter of 2023 were collected and analyzed. Detailed examinations of gender, age, reporter identity, and other aspects were conducted to reveal the fundamental characteristics of Asenapine-related adverse events. Signal mining techniques were employed to systematically evaluate various adverse reactions associated with Asenapine.
RESULTS: The study found that adverse event reports involving Asenapine were more common among female patients, with the age group mainly distributed between 18 and 45 years. Physicians were the primary reporters of adverse events, and psychiatric disorders, neurological disorders, and gastrointestinal disorders were the most common areas affected by adverse reactions. In addition to known adverse reactions, potential risks not mentioned in the drug label were identified, such as anosognosia, attentional drift, and psychogenic compensation disorder.
CONCLUSIONS: Asenapine carries the risk of various adverse reactions alongside its therapeutic effects. In clinical practice, physicians should closely monitor the occurrence of neurological disorders, psychiatric disorders, and gastrointestinal system disorders.

BACKGROUND: Treatment with different antipsychotics can lead to various metabolic side effects in patients with psychosis, impacting long-term prognosis. This study aimed to compare the changes and clinical efficacy of insulin resistance in patients treated with olanzapine and ziprasidone.
METHODS: A retrospective analysis was conducted on the clinical data of 80 patients with schizophrenia. The patients were divided into olanzapine treatment group and ziprasidone treatment group. Parameters including body weight, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), insulin resistance index, and Positive and Negative Syndrome Scale (PANSS) scores were recorded and compared before and after treatment.
RESULTS: BMI, FPG, FPI, homeostatic model assessment of insulin resistance (HOMA-IR), CHO, TG and LDL in both groups were significantly higher than before treatment (p < 0.05). These parameters were significantly higher in the olanzapine group than in the ziprasidone group (p < 0.05). The level of HDL in both groups was significantly decreased after treatment, and the level of HDL in the olanzapine group was significantly lower than that in the ziprasidone group after treatment (p < 0.05). After treatment, the total score and score of PANSS in both groups were significantly lower than before treatment (p < 0.05). After treatment, there was no significant difference in total score and PANSS score between both groups (p > 0.05). The incidence of insulin resistance (IR) was significantly higher in the olanzapine group compared to the ziprasidone group (χ2 = 4.021, p < 0.05). In the IR group, BMI, FPG, FPI, TG, and LDL levels were higher than in the non-IR group (p < 0.05). Multivariate analysis indicated that BMI, FPG, FPI, TG, and LDL were independent risk factors for IR (odd ratio (OR) >1, p < 0.05).
CONCLUSIONS: Treatment with olanzapine and ziprasidone improves clinical symptoms in patients with schizophrenia, but increases the risk of insulin resistance. The metabolic side effects of olanzapine are more pronounced.

BACKGROUND: Schizophrenia is a debilitating psychiatric disorder with diverse cognitive impairments. Insulin-like growth factor binding protein 1 (IGFBP-1), a ubiquitous negative regulator of IGF signaling, crosses the blood-brain barrier after peripheral synthesis. Given the crucial role of IGF signaling in cognitive function, we reasoned that altered serum IGFBP-1 concentrations might be associated with cognitive impairments in schizophrenia. To test this hypothesis, we examined the relationship between serum IGFBP-1 levels and cognitive performance in both medicated and treatment-resistant schizophrenia (TRS) patients.
METHODS: Serum IGFBP-1 was measured in 31 TRS patients, 49 chronic medicated schizophrenia (CMS) patients, and 53 healthy controls. Clinical symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS) and cognitive functions using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
RESULTS: Both TRS and CMS patients exhibited cognitive deficits compared to healthy controls (p < 0.05). Serum IGFBP-1 concentration differed significantly among groups (F=36.805, p < 0.001) and post hoc tests demonstrated significantly higher concentrations in both schizophrenia groups compared to controls (p < 0.001). Further, serum IGFBP-1 concentration was higher in the TRS group than the CMS group (p = 0.048). Correlation analysis identified a significant relationship between serum IGFBP-1 and attention in the TRS group (r = 0.411, p = 0.021), immediate memory in the CMS group (r = -0.417, p = 0.003), and RBANS total score in the CMS group (r = -0.368, p = 0.009). Multiple regression analysis adjusting for confounding factors revealed that serum IGFBP-1 was independently associated with attention in TRS patients (p = 0.016, 95 %CI. 0.002-0.015) and immediate memory in CMS patients (p = 0.022, 95 %CI-0.012 to -0.001).
CONCLUSIONS: Elevated serum IGFBP-1 concentration may serve as a predictive biomarker for distinct cognitive deficits in TRS and CMS patients. Further investigations are warranted.

BACKGROUND: Many articles suggest that clozapine was strongly associated with a higher incidence of new-onset diabetes mellitus, and the issue has remained unsettled. Many articles have compared clozapine with FGAs, but few have compared clozapine with SGAs. We aimed to compare the risk of new-onset diabetes mellitus in adults with schizophrenia treated with clozapine and other SGAs.
METHODS: We conducted a comprehensive search of databases from their inception up until August 26, 2023. The specific databases include PubMed, Embase and others. We included non-randomized controlled trials involving the use of SGAs such as clozapine, olanzapine, risperidone, quetiapine, amisulpride, and zotepine, with a focus on new-onset diabetes mellitus as an outcome. We utilized odds ratio with 95 % credible intervals (95 % CI) as our effect size measures. The study protocol is registered with PROSPERO, number CRD42024511280.
RESULTS: We included 7 studies with sufficient data to include in the meta-analysis. A total of eight studies with 641,48 participants met the eligibility criteria. The OR of the incidence rates of new-onset diabetes between clozapine and olanzapine was 0.95 (95 % CI:[0.82-1.09]), between clozapine and risperidone was 1.25 (95 % CI: [1.09-1.44]), between clozapine and quetiapine was 1.44 (95 % CI: [0.92-2.25]).
CONCLUSIONS: In patients with schizophrenia, clozapine has been found to have a higher rate of new-onset diabetes mellitus compared to risperidone. However, there was no significant difference in incidence rate between clozapine versus olanzapine and quetiapine. These findings can assist clinicians in balancing the risks and benefits of those drugs.

The dopamine D2 receptor (DRD2) represents a pivotal target for therapeutic intervention in the treatment of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and Parkinson\'s disease. The successful discovery of numerous effective DRD2 inhibitors has led to their clinical application and ongoing evaluation in various clinical trials. This review explores the synthetic approaches and clinical applications of prototypical small-molecule DRD2 inhibitors that have received approval or are currently undergoing clinical trials, highlighting their therapeutic potential and challenges. The synthesis of these inhibitors employs various chemical strategies, including modifications of phenothiazine and butyrophenone structures, which have yielded significant antipsychotic agents like chlorpromazine and haloperidol. Additionally, newer classes of inhibitors, such as aripiprazole, exhibit partial agonist activity at DRD2, offering a unique therapeutic profile. Clinically, DRD2 inhibitors demonstrate efficacy in managing positive symptoms of schizophrenia, manic episodes in bipolar disorder, and dopaminergic imbalance in Parkinson\'s disease. However, the emergence of adverse effects, including tardive dyskinesia, extrapyramidal symptoms and metabolic syndrome, presents substantial challenges. Advances in the development of second-generation antipsychotics aim to balance efficacy with a better side effect profile by targeting additional neurotransmitter receptors. This review aims to deliver an overview of the synthesis and clinical applications of representative small-molecule DRD2 inhibitors across various clinical phases, thereby offering strategic insights for the advancement of DRD2 inhibitor development.