ziprasidone / Generic mfg. - LARVOL DELTA

Interim data from ENIGMA – TRS 1 study of evenamide as add on therapy to antipsychotic Standard of Care in patients with treatment resistant schizophrenia (TRS). Difficulties in performing TRS study with TRRIP criteria: the CRO experience (WFSBP 2026) - "One aspect of the ENIGMA – TRS 1 study assesses plasma concentrations of standard of care as selected antipsychotics: Aripiprazole, Brexpiprazole, Cariprazine, Clozapine, Lurasidone, Olanzapine, Paliperidone, Quetiapine, Risperidone and Ziprasidone for subjects treated with those antipsychotics with daily therapeutic doses meeting local product labels requirements and correlated those with minimal duration of 6 weeks treatment with any of those medications. As the study is performed in 20 countries worldwide major issues reside in getting approval by all regulatory approvals, languages use for the rating instruments as well as for the training of the raters. Based on hundreds of patients entering screening, a large proportion failed the screening phase because of lack of adequate concentration of the primary AP. Difficulties have been noticed in ensuring adequate documentation of previous AP failures."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Evidence based interventions for bipolar disorder across phases and age groups: living umbrella review, evaluation, analysis, and communication hub (U-REACH) project. (PubMed, BMJ) - "The EBI-BD tool can help clinicians make evidence based, personalised treatment decisions for bipolar disorder. This resource can inform clinical guidelines and provides a foundation for continuously improving bipolar disorder care as new evidence emerges."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Mood Disorders • Psychiatry

Receptor Contribution Reallocation After Removal of Literature-Derived Weights: A Secondary Sensitivity Analysis of the Integrated Ki-DDD-TWAS Pipeline for Antipsychotic Lipid-Trait Prioritization. (PubMed, Cureus) - "The model most strongly under-ranked paliperidone versus the supplied 12-drug comparator, while ziprasidone rose under uniform weighting. Removing HRH1 produced the largest rank shifts, particularly for levomepromazine, promazine, and acepromazine...The framework supports dual reporting of clinically anchored weighted and discovery-oriented uniform models as an internal sensitivity strategy only. It is not externally validated, does not predict patient-level outcomes, and should not be interpreted as estimating clinical metabolic risk or establishing receptor-level causality."

Journal • CNS Disorders • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • ADRB2 • DRD2 • HTR2A • SLC6A4

Impact of nutritional factors on the pharmacokinetics of antipsychotics - a systematic review. (PubMed, Psychiatry Res) - "Nutritional factors are a significant source of PK variability in antipsychotic treatment. The results underscore the necessity of standardized administration guidelines (e.g., "take with food" for ziprasidone or "fasted" for amisulpride) to ensure predictable plasma levels and optimize therapeutic outcomes in clinical practice."

Journal • PK/PD data • Review • CNS Disorders • Psychiatry

Efficacy, acceptability, and related outcomes of pharmacological interventions for acute bipolar mania: a systematic review and dose-related network meta-analysis across different age groups. (PubMed, J Affect Disord) - "Our findings are consistent with previous NMAs and current guidelines, expanding the current knowledge base while concurrently appraising different drugs, doses, and age groups."

Journal • Retrospective data • Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Pediatrics • Psychiatry

The efficacy and safety of paliperidone palmitate injection(II) as a replacement for oral medication in the treatment of schizophrenia (ChiCTR) - P4 | N=120 | Not yet recruiting | Sponsor: Nanjing Brain Hospital; Nanjing Brain Hospital

New P4 trial • CNS Disorders • Psychiatry • Schizophrenia

Heterogeneity and concentration-dependence of ionic channel mechanisms underlying ventricular repolarization prolongation induced by atypical antipsychotics. (PubMed, Toxicol Appl Pharmacol) - "Using whole-cell patch-clamp techniques, we recorded action potentials and major transmembrane ionic currents (IKr, IKs, IK1, Ito, and INa) in primary adult mouse ventricular myocytes exposed to five AAPs (olanzapine, quetiapine, clozapine, ziprasidone, and risperidone) at a moderate therapeutic concentration. In conclusion, at therapeutic concentrations, AAPs delay ventricular repolarization via distinct ion channel blockades. At supratherapeutic doses, the loss of channel selectivity and synergistic multi-channel blockade constitute the core mechanism for malignant arrhythmias during drug overdose, highlighting the need to consider drug-specific multi-channel profiles in future clinical cardiac safety evaluations."

Heterogeneity • Journal • Cardiovascular • CNS Disorders

Cardiac Safety Profile of Ziprasidone: A Real-World Pharmacovigilance Study Using FAERS and Network Toxicology. (PubMed, Curr Neuropharmacol) - "The findings from FAERS pharmacovigilance analysis suggest a potential association between ziprasidone exposure and cardiac adverse events. Toxicological network analysis further indicated that the calcium signaling pathway may be involved in the underlying molecular mechanisms."

Adverse events • Journal • Real-world evidence • Cardiovascular • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

Proposal To Develop A Rapid And Cost-Effective Diagnostic Test For Schizophrenia (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: University of Arizona | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2026 ➔ Feb 2027 | Trial primary completion date: Feb 2026 ➔ Feb 2027

Enrollment closed • HEOR • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Cardiovascular Effects of Droperidol: A Clinically-Focused Review for the Consultation-Liaison and Emergency Psychiatrist. (PubMed, J Acad Consult Liaison Psychiatry) - "Despite practical advantages for agitation, the use of droperidol is associated with moderate-to-high-risk QTc prolongation, comparable to ziprasidone and greater than intravenous haloperidol. Although droperidol use does not appear to be associated with an increased risk for arrythmia, alternative agents may be preferred in patients with other risk factors for arrythmias. Consultation-liaison and emergency psychiatrists should be familiar with these risks."

Journal • Review • Cardiovascular • Psychiatry

Pharmacological and non-pharmacological interventions for altered consciousness and agitation following paediatric acquired brain injury: a scoping literature review. (PubMed, Disabil Rehabil) - "The highest quality studies investigated the use of dopaminergic agents (amantadine and pramipexole), an atypical antipsychotic (ziprasidone), multidisciplinary rehabilitation approaches, and sensory stimulation. This review highlights the paucity of high-quality experimental studies investigating the use of pharmacological and non-pharmacological approaches to managing altered consciousness and agitation for children following ABI. Further research is needed to determine their efficacy and inform recommendations to guide clinical practice."

Journal • Review • CNS Disorders • Pediatrics • Vascular Neurology

MAIA: Maternal And Infant Antipsychotic Study (clinicaltrials.gov) - P=N/A | N=74 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | N=200 ➔ 74 | Trial primary completion date: Jun 2027 ➔ Jan 2028

Enrollment change • Trial primary completion date • CNS Disorders

BARD1 phase separation orchestrates a repair hub by enriching XRCC5 to drive chemoresistance in glioma. (PubMed, Life Sci) - "Through structure-based virtual screening, our results suggest that Ziprasidone and Apomorphine may disrupt the BARD1-XRCC5 interaction...Our findings unveil a novel LLPS-mediated mechanism by which BARD1 confers TMZ resistance in GBM, positioning it as a prognostic marker and a therapeutic target. Targeting the BARD1-XRCC5 axis presents a promising strategy to overcome chemoresistance."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • BARD1 • BRCA1 • XRCC5

Risk of extrapyramidal symptoms associated with antipsychotic drugs in children and adolescents: a systematic review and meta-analysis of double-blind randomised placebo-controlled trials. (PubMed, Res Sq) - "The highest risk estimates were observed for ziprasidone, risperidone, and aripiprazole. Careful risk-benefit assessment, tailored prescribing, and systematic monitoring of EPS in routine paediatric clinical practice are warranted."

Journal • Retrospective data • CNS Disorders • Developmental Disorders • Pediatrics • Psychiatry

Antipsychotic selection in combination with electroconvulsive therapy for acute schizophrenia: differential efficacy and safety profiles from a real world study. (PubMed, BMC Psychiatry) - P=N/A | "In this observational study of patients with acute phase schizophrenia, the comparative effectiveness and tolerability of antipsychotic medications combined with ECT appeared to differ depending on the specific agent used. These preliminary observations require confirmation in randomized controlled trials before guiding individualized treatment selection."

Journal • Real-world evidence • CNS Disorders • Psychiatry • Schizophrenia

When all treatment fails in neuroleptic malignant syndrome: two refractory cases compared with two recoveries (APA 2026) - "Cases: Case 1: A 38-year-old male with schizophrenia on ziprasidone and haloperidol, independent in basic activities of daily living (ADLs), presented with altered mental status (AMS), extreme hyperthermia of 107°F, creatine kinase (CK) 1260 U/L, creatinine (Cr) 1.82 mg/dL, transaminitis, ventricular tachycardia prompting cardioversion, and early vasopressor requirement...Memantine and amantadine were used for augmentation...Case 2: A 49-year-old male independent in ADLs with a history of schizophrenia on olanzapine, paliperidone palmitate (long-acting injectable), quetiapine, and cariprazine, presented with AMS, fever 102°F, severe rigidity, CK 5366 U/L, Cr 1,84 mg/dL, transaminitis...Despite treatment with dantrolene, aggressive supportive care, benzodiazepine optimization, and 20 ECT sessions, the patient did not recover to baseline functioning and was discharged to a nursing facility with persistent deficits...He was managed with antipsychotic..."

Clinical • Acute Kidney Injury • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • Mental Retardation • Nephrology • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Schizophrenia • Ventricular Tachycardia

Management Challenges in Patients with Sickle Cell Disease and Schizophrenia: Case-Based Review and Clinical Recommendations (APA 2026) - "Interdisciplinary collaboration emphasized hydration, pain management with hydrocodone-acetaminophen, and caregiver education, which supported psychiatric stabilization and reduced risk of decompensation...Based on this case and the limited literature, olanzapine, quetiapine, ziprasidone, and aripiprazole appear to be safer antipsychotic options in SCD, as they are less likely to cause neutropenia or intrinsic kidney injury... Patients with SCD and schizophrenia require individualized, collaborative care. This case highlights the importance of careful medication selection, interdisciplinary coordination, and proactive education. More research is needed to develop evidence-based guidelines for psychiatric management in this population."

Clinical • Review • Acute Kidney Injury • Agranulocytosis • Chronic Kidney Disease • CNS Disorders • Developmental Disorders • Genetic Disorders • Granulocytopenia • Hematological Disorders • Leukopenia • Mental Retardation • Nephrology • Neutropenia • Psychiatry • Renal Disease • Schizophrenia • Sickle Cell Disease

Chill Pill: A Case Series on Antipsychotic-Induced Hypothermia (APA 2026) - "Psychiatric evaluation was notable for excited catatonia and he was started on lorazepam. He was eventually discharged on abilify 5mg daily for psychosis and catatonia without recurrence of hypothermia...He was on risperidone and zyprexa at the jail...Risperidone was switched to ziprasidone; despite this, she was hospitalized three times over six months for hypothermia... Given multiple risk factors of correctional settings, including poor temperature regulation, limited access to insulating clothing, and poorly managed medical comorbidities, it is difficult to attribute these patients' development of hypothermia to antipsychotic exposure alone. AIH may be overstated in the literature, and distract from proper diagnosis and management. Thorough medical work-up is necessary to exclude all other etiologies of hypothermia before antipsychotics are discontinued."

Clinical • CNS Disorders • Diabetes • Endocrine Disorders • Epilepsy • Hypoglycemia • Metabolic Disorders • Schizophrenia • Septic Shock • Type 2 Diabetes Mellitus

Risk of Akathisia with Antipsychotics and Its Treatment: Is Propranolol still the best option in 2025? (APA 2026) - " We performed a literature review using PubMed and PubMed Central databases using keywords in different combinations, like "akathisia and antipsychotics", "akathisia management", "akathisia and propranolol", "akathisia and ECT", "akathisia and benzodiazepines", "akathisia and mirtazapine", "akathisia and biperiden/anticholinergics", and "akathisia and vitamin B6" etc. We included data from thirty-nine observational, analytical, and review articles published in the last five years and summarized the key findings. Observations: Akathisia has been classically associated with first-generation high-potency antipsychotics like haloperidol. Among atypical antipsychotics Risperidone (mean dose of 5.4mg/day) and Lurasidone (mean dose of 240mg/day), Cariprazine and Ziprasidone have been found causing akathisia at higher therapeutic dosages, while the risk is found to be lower with Sertindole..."

CNS Disorders

Multi-objective optimization in population pharmacokinetic model selection and optimization: application of NSGA-II in pyDarwin. (PubMed, J Pharmacokinet Pharmacodyn) - "Concentration measurements of 17-DMAG, quetiapine, clozapine and ziprasidone were applied to build population pharmacokinetic models through traditional stepwise search, machine learning based single-objective hybrid genetic algorithm (SOHGA) and MOO. The optimal model selected by SOHGA appeared on the Pareto front for DMAG, ziprasidone and clozapine datasets. Overall, MOO provides objective transparency to the cost of tradeoffs between competing model objectives, allowing researchers to better contextualize subjective criteria (e.g., biological plausibility, improvements in diagnostic plots) when aligning model selection with clinical context."

Journal • PK/PD data

Diagnosis and Medication Treatment of Schizophrenia in Adolescents. (PubMed, Drugs) - "Randomized controlled trials and open-label studies support the efficacy of risperidone, aripiprazole, olanzapine, quetiapine, paliperidone, lurasidone, and brexpiprazole in reducing psychotic symptoms in adolescents. In contrast, ziprasidone and asenapine have not demonstrated clear benefit in treatment of schizophrenia in youth. Similar to studies in adults, evidence from pediatric clinical trials suggests that clozapine remains the most effective option for treatment-resistant adolescent schizophrenia, although its use requires close monitoring for hematologic and other adverse effects...However, the relative paucity of pediatric-specific data compared with adult populations underscores the importance of continued research to guide clinical practice. In the meantime, accurate diagnosis, early intervention, and vigilant monitoring of both therapeutic response and side effects remain essential to optimizing outcomes for youth with schizophrenia."

Journal • Review • Anesthesia • CNS Disorders • Hematological Disorders • Metabolic Disorders • Pediatrics • Psychiatry • Schizophrenia

Seizures Risk Related to Atypical Antipsychotics: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS). (PubMed, Alpha Psychiatry) - "This pharmacovigilance study aimed to characterize the spectrum of seizure-related adverse events (AEs) associated with eight commonly used atypical antipsychotics (AAPs)-clozapine, quetiapine, olanzapine, aripiprazole, ziprasidone, risperidone, lurasidone, and paliperidone-based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and to explore potential receptor mechanisms underlying AAP-related seizures. Clinicians should consider these differential risks, especially when prescribing for patients with predisposing factors, and maintain vigilance for specific seizures types. These findings warrant further validation through prospective studies and clinical causality assessments."

Adverse events • Journal • CNS Disorders • Epilepsy

Risk factors for drug-related gestational diabetes mellitus: a real-world pharmacovigilance study based on the FAERS database. (PubMed, BMC Pregnancy Childbirth) - "This study identified 12 drugs that may be independent risk factors for GDM, including quetiapine, aripiprazole, olanzapine, prednisolone, venlafaxine, risperidone, escitalopram, clozapine, mirtazapine, ziprasidone, rosuvastatin, and trazodone. The established predictive model has certain clinical value, and the potential mechanisms by which antipsychotic drugs may lead to GDM were further analyzed. These results provide potential clues for the early identification of GDM and early warning of suspected drugs, and offer a reference for further exploration of its pathogenesis."

Adverse events • Journal • Real-world evidence • CNS Disorders • Diabetes • Gestational Diabetes • Metabolic Disorders • DRD2 • IR • KCNH2

Transitioning from clozapine to Cobenfy (xanomeline-trospium chloride) in treatment resistant schizophrenia and clozapine induced OCD. (PubMed, BMC Psychiatry) - "This case highlights a successful switch from clozapine to xanomeline-trospium for management of chronic schizophrenia and clozapine induced OCD. The patient's improvement raises important considerations regarding clozapine-induced OCD, cautious discontinuation, and the benefit of muscarinic receptor agonists. Xanomeline-trospium may represent a viable alternative for patients intolerant of clozapine."

Journal • CNS Disorders • Hematological Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • Schizophrenia • Suicidal Ideation

Exploring Risk Drugs and Mechanisms in Dystonia: Insights from Pharmacovigilance and Proteogenomics. (PubMed, Curr Neuropharmacol) - "Our study highlights risk drugs for dystonia and their molecular mechanisms and provides evidence for the safer and more individualized use of antipsychotics, antidepressants, and other drugs related to dystonia."

Adverse events • Journal • CNS Disorders • Dystonia • Essential Tremor • Movement Disorders • Parkinson's Disease