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.

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect.

On the example of a patient with a mixed affective episode within the framework of bipolar affective disorder, the clinical features of this psychopathological condition, the difficulties of diagnosis and selection of therapy in mixed states are presented. The use of the modern atypical antipsychotic ziprasidone in this category of patients is argued.
На примере пациентки со смешанным аффективным эпизодом в рамках биполярного аффективного расстройства представлены клинические особенности данного психопатологического состояния, трудности диагностики и подбора терапии данных состояний. Аргументировано использование современного атипичного антипсихотика зипрасидона у этой категории пациентов.

Quetiapine, a pharmacological agent within the class of atypical antipsychotics, is characterized by its efficacy in mood stabilization and its role in the modulation of serotonergic and dopaminergic pathways. Its therapeutic utility is broad, encompassing the management of acute psychotic episodes, schizophrenia, bipolar disorder, and treatment-resistant depressive states. Quetiapine\'s effectiveness extends to depressive disorders that do not exhibit classic psychotic features, with a side effect profile that is less burdensome than many alternative psychotropic medications. Its versatility in addressing a range of psychiatric conditions is useful in the psychopharmacological management of mood and thought disorders. However, like all drugs, quetiapine may have different effects relative to the individual. It is imperative to approach the administration of quetiapine carefully, ensuring any adverse effects are ameliorated for beneficial therapeutic outcomes. In this case report, we present a psychosis-naive 42-year-old male who developed psychotic symptoms after beginning a quetiapine regimen in order to manage major depressive disorder with suicidal ideation. Clinical suspicion of quetiapine-induced psychosis was a diagnosis considered due to symptom remission secondary to ziprasidone in the place of quetiapine. The determination of a suspected adverse drug reaction can utilize the Naranjo scale to demonstrate the likelihood of an adverse drug reaction. This patient scored a three on the Naranjo scale, indicating a possible adverse effect from quetiapine. Other potential etiologies of psychosis include medication-induced psychosis, major depressive disorder exacerbation, cocaine use/withdrawal, and brief psychotic disorder. Quetiapine-induced psychosis has not been described in the current literature, and therefore, this case report is solely based on clinical evaluation and is intended for educational purposes due to possible confounding factors and etiologies.

In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (t_imp. V, t_imp. V - t_imp. I, S and ) was studied by Box-Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained. The design space was computed (π ≥ 80%), and a working point was selected: initial methanol fraction 38.5%, final methanol fraction 77.5%, and gradient duration 16.25 min. Furthermore, the quantitative robustness of the developed method was tested using the Plackett-Burman design. P_imp II and P_imp V were found to be significantly affected, the first by mobile phase flow rate and the second by gradient duration. Finally, the method was validated, and its reliability for routine quality control in capsules was confirmed.

The feasibility of using lipid-polymer hybrid (LPH) nanocarriers as a potential platform for the intranasal delivery of ziprasidone (ZP), a second-generation antipsychotic, was explored. Different ZP-loaded LPH composed of a PLGA core and cholesterol-lecithin lipid coat were prepared using a single step nano-precipitation self-assembly technique. Modulation of polymer, lipid and drug amounts, as well as stirring-speed-optimized LPH with a particle size of 97.56 ± 4.55 nm and a ZP entrapment efficiency (EE%) of 97.98 ± 1.22%. The brain deposition and pharmacokinetics studies proved the efficiency of LPH to traverse the blood-brain barrier (BBB) following intranasal delivery with a 3.9-fold increase in targeting efficiency compared to the intravenous (IV) ZP solution with a direct nose-to-brain transport percentage (DTP) of 74.68%. The ZP-LPH showed enhanced antipsychotic activity in terms of animals\' hypermobility over an IV drug solution in schizophrenic rats. The obtained results showed that the fabricated LPH was able to improve ZP brain uptake and proved its antipsychotic efficiency.

Packed with hemoglobin, an essential protein for oxygen transport, human erythrocytes are a suitable model system for testing the pleiotropic effects of lipophilic drugs. Our study investigated the interaction between antipsychotic drugs clozapine, ziprasidone, sertindole, and human hemoglobin under simulated physiological conditions. Analysis of protein fluorescence quenching at different temperatures and data obtained from the van\'t Hoff diagram and molecular docking indicate that the interactions are static and that the tetrameric human hemoglobin has one binding site for all drugs in the central cavity near αβ interfaces and is dominantly mediated through hydrophobic forces. The association constants were lower-moderate strength (~104 M-1), the highest observed for clozapine (2.2 × 104 M-1 at 25 °C). The clozapine binding showed \"friendly\" effects: increased α-helical content, a higher melting point, and protein protection from free radical-mediated oxidation. On the other hand, bound ziprasidone and sertindole had a slightly pro-oxidative effect, increasing ferrihemoglobin content, a possible \"foe\". Since the interaction of proteins with drugs plays a vital role in their pharmacokinetic and pharmacodynamic properties, the physiological significance of the obtained findings is briefly discussed.

UNASSIGNED: Schizophrenia usually begins with prodromal symptoms in adolescence. In 39% of patients, onset of psychotic symptoms occurs prior to age 19. Advances in the treatment of psychosis with medications over the last decade are reviewed in this paper.
UNASSIGNED: Understanding how to prescribe antipsychotics early in schizophrenia requires an understanding of the pathophysiology of the disease. The current structure of the dopamine hypothesis is reviewed. Risperidone, paliperidone, olanzapine, quetiapine, and aripiprazole have become established treatments prior to 2012. Since 2012, lurasidone (2017) and brexpiprazole (2022) have also been approved. Lurasidone was approved based on placebo-controlled studies, but brexpiprazole has been approved on the bases of open safety trials. In comparative trials, aripiprazole was better tolerated and less likely to cause hyperprolactinemia and metabolic abnormalities.
UNASSIGNED: Antipsychotics can induce adaptive changes in the brain that predispose patients to future problems such as tardive dyskinesia and supersensitivity psychosis. When pathophysiology of schizophrenia, and a clear understanding of the pharmacology of existing antipsychotics are included in the evidence-based analysis, use of partial agonists, which are less likely to induce adaptive changes in the brain and less likely to induce metabolic and prolactin side effects, become the preferred agents.

Ziprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia.
A total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10-40 mg daily and started sequentially with oral ziprasidone 40-80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120-160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment.
Out of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2-Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported.
Ziprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients.
The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn : ChiCTR-OIC-16007970.

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