Antipsychotic Research Articles

Antipsychotic medications are prescribed in the pediatric population for various psychiatric conditions, such as schizophrenia, autism spectrum disorder, mood disorders, and other disruptive behaviors. However, the use of antipsychotic medications, particularly atypical antipsychotic medications, has raised concerns because of their potential to cause weight gain. This review aims to compare the effects of different antipsychotic medications on weight gain in children and adolescents, particularly patients with childhood-onset schizophrenia, after 6-8 weeks of antipsychotic treatment. We searched 5 online databases. Seventeen articles were included with 1360 participants being enrolled. Meta-insight was used for network meta-analysis. We used body weight gain (kilogram) collected in the included studies for calculation. Olanzapine caused the most significant weight gain. The ranking of clozapine is not as high as in adult studies. In contrast, molindone may actually reduce weight. Weight gain in patients with schizophrenia is more clinically significant than in the whole participants. Our study indicated the effects of different antipsychotic medications on body weight gain among children. Childhood-onset schizophrenia may represent a more vulnerable group. Future studies exploring genetic and physiologic risk factors for weight gain, and potential preventive strategies, are needed.

Schizophrenia spectrum disorders (SSD) are debilitating psychiatric illnesses that require extensive pharmacologic, cognitive, and functional management. SSD patients are often prescribed different medications, most commonly antipsychotics, which bear numerous side effects. Recently, accumulating evidence has shown epigenetic aging changes in SSD. However, the effects of antipsychotic medications on this phenomenon remain unexplored.We investigated whether antipsychotic medications are associated with epigenetic age acceleration (EAA) in 153 SSD patients. EAA was estimated using six different epigenetic clocks, based on the methylation patterns of peripheral blood cells.The analysis revealed some evidence of aging deceleration based on the Hannum DNAm Age in individuals on antipsychotic polypharmacy, relative to their monopharmacy counterparts (mean difference=-0.59 years, p=0.0109), which was only nearing significance after adjusting for multiple comparisons (padjusted=0.0654). In sex-specific analysis, only females displayed significantly decelerated epigenetic aging in the polypharmacy group in three of the six clocks. Furthermore, we observed no dose-dependent effects of antipsychotics on EAA in all clocks using three dose standardization methods (daily defined dose, chlorpromazine equivalents, and percent of maximum allowed dose).The findings suggest that antipsychotic treatment may modulate biological aging in SSD; however, this effect is not dose-dependent. Moreover, there appears to be an interplay between sex, polypharmacy, and epigenetic aging. These findings contribute to our understanding of the biological effects of antipsychotic treatment, and future research in this area is key for weighing the benefits and the risks of pharmacological management of SSD.

Does adjunctive electro-convulsive therapy improve the speed of treatment response in schizophrenia? A systematic review and week-by-week meta-analyses of controlled clinical trials.

Brain histaminergic system: An emerging target for the treatment of feeding and eating-related disorders.

Droperidol vs. haloperidol for abdominal pain.

Synthesis of 2-(3-aminopropyl)benzopyrans as potential antipsychotic agents targeting D2/D3 and 5-HT2A receptors.

Dual emissive nanoprobe for reliable detection of antipsychotic drug fluphenazine using silicon nanoparticles and eosin dye

Efficacy of continuous theta burst stimulation (cTBS) in the treatment of auditory verbal hallucinations in Schizophrenia: A randomized controlled trial.

A sensitive colorimetric immunosensor for clozapine, norclozapine, and clozapine-N-oxide simultaneous detection based on monoclonal antibodies preparation with homogeneous cross-reactivity.

Reducing burst release and enhancing sustained release in SAIB-based implants: The role of polyphenol-modification.

The gut-brain axis (GBA), a bidirectional communication system between the gut and the brain, has emerged as a critical player in mental health. The interest in the connection between anxiety disorders (AD) and the gut microbiota is growing. This paper provides an overview of gut microbiota's role in dysregulation in anxiety, including alterations in gut microbiota (dysbiosis), leaky gut, metabolic endotoxemia, and the effect of antipsychotic medications. The mechanisms underlying the gut microbiota-anxiety (GMA) connection, such as neurotransmitter production, immune dysregulation, and GBA communication, are discussed. Furthermore, the paper explores gut microbiota- based therapeutic strategies, including probiotics, prebiotics, symbiotics, fecal microbiota transplantation, and dietary interventions, as potential approaches for anxiety management. This research field's clinical implications and future directions are also examined, underscoring that more studies are needed on gut microbiota's role in anxiety disorders. The conclusion highlights the importance of this ongoing research and the potential for personalized therapeutic interventions, instilling hope and optimism for the future of anxiety management and providing reassurance about the potential for personalized therapeutic interventions in this field.

Hospitalization in women with psychosis: An age-based proxy analysis for menopause.

Clozapine, a highly effective antipsychotic medication, is associated with rare but potentially life-threatening neutropenia. In February 2025, the US Food and Drug Administration (FDA) eliminated its clozapine Risk Evaluation and Mitigation Strategies (REMS) program, which required documented absolute neutrophil count (ANC) lab results prior to clozapine dispensation. Considering the FDA decision, the purpose of this study was to examine the prevalence and patient-level factors associated with clozapine-associated neutropenia in a large, diverse, US-based integrated health system. This was a retrospective cohort study of adult Kaiser Permanente Northern California members who initiated clozapine therapy between January 2021 and December 2022. Data were extracted from KPNC's electronic health record, including sociodemographic and clinical characteristics, medication fills, and ANC values. The main outcome was any neutropenic event within two years of clozapine initiation, classified as mild (ANC = 1000-1499/μL) or severe (ANC < 1000/μL). Among 402 patients, 10 (2.5%) experienced neutropenia within 24 months of starting clozapine. Eight cases were mild, and two were severe, with one resulting in death. Race differed significantly between those who experienced neutropenia and those who did not (p = 0.038). The mean clozapine dose at the time of neutropenia was 192.5 mg, with significant differences between mild and severe cases (p = 0.015). Logistic regression analyses showed no significant associations between neutropenia and patient-level sociodemographic or clinical characteristics. Clozapine-related neutropenia was rare and typically transient, but it can be life-threatening. Continued adherence to the manufacturer's recommendations for ANC monitoring is warranted to ensure patient safety.

Hippocampal subfield activity in schizophrenia: Effects of the disease course.

Antipsychotic drugs are the mainstay of schizophrenia treatment; yet, controversy persists regarding their relative efficacy and side effects, and guideline recommendations on efficacy differences are particularly vague. The aim of this trial was to compare seven antipsychotics in acutely ill patients with schizophrenia. The authors performed a multicenter (32 hospitals), industry-independent, parallel, assessor-blinded, flexible-dosage randomized trial (Schizophrenia in Non-Occidental Participants). Eligible inpatients 18-45 years of age with schizophrenia experiencing acute exacerbation were recruited and randomized to 6 weeks of monotherapy with one of seven antipsychotic drugs: olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, perphenazine, and haloperidol. A total of 3,067 patients were randomized, of whom 82% completed follow-up. The mixed model indicated significant differences in the primary outcome percentage change in Positive and Negative Syndrome Scale (PANSS) score between the antipsychotics. At week 6, olanzapine and risperidone showed a significantly higher percentage change in PANSS score than aripiprazole, ziprasidone, and quetiapine (mean differences: 5.52-7.93) but not haloperidol or perphenazine. Olanzapine was associated with the highest risk of weight gain (relative risk: 1.44-3.22). Aripiprazole was associated with lower risk of hyperprolactinemia than all the other drugs (relative risks: 0.11-0.21). Ziprasidone and aripiprazole were associated with lower risks of weight gain and metabolic side effects. Haloperidol was associated with a higher risk of extrapyramidal symptoms than all other drugs (relative risks: 0.13-0.61). Aripiprazole was least sedating (relative risks: 0.30-0.39). Olanzapine and risperidone showed lower all-cause discontinuation rates than ziprasidone and haloperidol (hazard ratios: 0.61-0.73). This trial fills important knowledge gaps in acute antipsychotic treatment of schizophrenia. It confirms hierarchies in efficacy and side effects of antipsychotics from related evidence.

Highlights - Aripiprazole and brexpiprazole showed significantly increased dissociation from the dopamine D2 receptor upon L94A mutation, indicating that their secondary pharmacophores interact with the secondary binding pocket.- Cariprazine, sharing an identical primary pharmacophore with aripiprazole, was unaffected by the secondary binding pocket mutation, suggesting a canonical binding pose at the dopamine D2 receptor.- In contrast to aripiprazole, cariprazine, and brexpiprazole, lumateperone lacked detectable dopamine D2 receptor efficacy in our assay.

Schizophrenia is among the serious mental illness affecting about 1% of the global population and ranking among the top ten causes of long-term disability. It is a major contributor to global disability and requires consistent adherence to antipsychotic medication for effective management. However, treatment non-adherence remains a significant challenge, particularly in Sub-Saharan Africa (SSA), where systemic barriers and cultural stigma further exacerbate the issue. This systematic review and meta-analysis aim to estimate the pooled prevalence of antipsychotic non-adherence among patients with schizophrenia in SSA and to identify the factors associated with treatment non-adherence. A systematic search was conducted across multiple databases, including PubMed, Cochrane, Scopus, African Index Medicus, and Google Scholar, for studies published before February 2025. This review has been registered with PROSPERO (registration number: CRD420251038674). Data were extracted using standardized forms, and study quality was assessed using the Joanna Briggs Institute (JBI) tools. A random-effects model was employed to estimate the pooled prevalence, with subgroup analyses and meta-regression conducted to explore sources of heterogeneity. This meta-analysis, which was conducted in SSA, included 16 full-text articles encompassing a total of 5,994 participants. The pooled prevalence of antipsychotic non-adherence was 45.30% (95% CI: 29.57–61.04%), with substantial heterogeneity observed (I2 = 99.51%). The review identified Several factors associated with treatment regimen non-adherence, including EPS (AOR = 3.95, 95% CI: 1.84–8.48), polypharmacy (AOR = 2.15, 95% CI: 1.56–2.96), substance use (AOR = 2.30, 95% CI: 1.43–3.71), alcohol use (AOR = 2.70, 95% CI: 1.21–5.99), perceived stigma (AOR = 2.58, 95% CI: 1.73–3.84), and lack of family support (AOR = 2.01, 95% CI: 1.33–3.04). The study reveals that nearly half of patients with schizophrenia in SSA exhibit non-adherence to antipsychotics, driven by treatment-related side effects, substance use, and socio-cultural barriers. Targeted interventions simplifying regimens, managing EPS, enhancing family involvement, and reducing stigma are urgently needed. Policymakers should prioritize mental health infrastructure and community education to improve adherence and outcomes in this vulnerable population.

Individuals affected by psychotic disorders often decide to have a trial of dose reduction or discontinuation of their antipsychotic medications; however, there is a lack of evidence-based guidance for this practice. There is limited knowledge on the different methods for dose reduction or discontinuation of antipsychotic medications in which methods might be the safest and most effective. This scoping review aims to identify methods of antipsychotic dose reduction and discontinuation, to develop a comprehensive inventory of tapering strategies. A systematic search was performed in PubMed, EMBASE, PsycINFO, and Cochrane to identify publications involving antipsychotic dose reduction or discontinuation. We included primary studies, systematic reviews, theoretical papers, and guidelines. A total of 9005 unique articles were identified, and full text screening was conducted on 459 of these. Thirty-two articles were included in the final analysis: 28 related to oral antipsychotic medications and 4 to long acting injectables. Three broad categories of dose reduction/discontinuation were identified-immediate, rapid (<4weeks), and gradual (short 4-26weeks and long≥26weeks). Further subtypes were identified, with reduction based on either the original starting dose or the most recent dose after the last reduction. The hyperbolic method estimates the dose reduction based on a gradual reduction in the D2 receptor occupancy. A wide range of antipsychotic tapering methods have been implemented internationally with no consensus on the best approach. The results of this scoping review could help to inform research on establishing the most effective methods of antipsychotic discontinuation.

Introduction Triple-negative breast cancer (TNBC) is a challenging subtype of breast cancer to treat because it lacks the expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). A significant majority of deaths related to cancer are caused by tumor metastasis and angiogenesis. Vascular endothelial growth factor receptor 2 (VEGFR2) plays a significant role in angiogenesis. Instead of developing new molecules, drug repurposing, also known as repositioning, seeks innovative uses for outdated drugs or those that fail due to ineffectiveness. Methods In this study, we performed high-throughput virtual screening of FDA approved drug library taken from Enamine bioactive collection targeting VEGFR proteins, and the top hit compounds analyzed by molecular dynamics simulations and MM-GBSA were considered for further in vitro analyses against human breast cancer cells, MDA-MB-231 and MDA-MB-468 cells followed by in ovo assay using the Chorioallantoic Membrane (CAM) model. Results The results revealed that risperidone was effective against triple-negative breast cancer, with IC50 values ranging from 46.53 to 49.76 µM. The findings of our study demonstrated that risperidone, an antipsychotic drug, could successfully inhibit human breast cancer cells in silico, in vitro and in ovo . Discussion We could prove that a structure-based drug repurposing approach is an effective strategy to produce a promising antiangiogenic repurposed drug that could also inhibit VEGFR2 in breast cancer. Although risperidone showed modest potency, its clinical availability and repurposing potential support further evaluation in preclinical and clinical settings.

New treatments for schizophrenia are urgently needed because existing antipsychotic drugs mainly improve positive symptoms, with minimal effect on cognitive deficits and negative symptoms. The approval of Karuna Therapeutics (KarXT) in 2024 marked a significant milestone, as it became the first antipsychotic drug to target muscarinic acetylcholine receptors (mAChRs) rather than dopamine receptors. Here, we provide a perspective on how targeting mAChRs might improve the positive, negative and cognitive symptoms of schizophrenia. First, we revisit the prevailing view that xanomeline acts primarily as a M1 and M4 mAChR partial agonist. Next, we examine potential pharmacological overlap with clozapine, focusing on actions at 5-HT1A, 5-HT2A and 5-HT7 receptors and consider whether 5-HT receptor subtype agonism, inverse agonism or antagonism could be important for therapeutic efficacy. We then review the brain systems and networks impacted by muscarinic receptor subtypes in the context of Research Domain Criteria (RDoC) domains. We propose that, based on their cellular and regional expression, muscarinic receptor subtypes impact several cortico-striatal-thalamo-cortical loops and interrelated networks to improve RDoC-informed sensorimotor, positive valence, social processes, arousal and regulation, and cognitive systems. Taken together, these data suggest that there are neurobiological reasons for optimism for muscarinic agents to improve the classically described positive, negative and cognitive symptoms of schizophrenia, although the relative contribution of each mAChR subtype (M1-M5) remains unclear. We propose that a multi-targeted approach combining actions at 5-HT1A and 5-HT7 receptors could provide additional therapeutic benefits across a range of RDoC domains and hence be of clinical benefit trans-diagonistically beyond schizophrenia.