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Introduction: Our objective was to conduct a systematic review and meta-analysis of adverse effects on sleep in patients with schizophrenia receiving antipsychotic treatment. Methods: A systematic search was performed in PubMed, Cochrane Central, Embase, Toxline, Ebsco, Virtual Health Library, Web of Science, SpringerLink, and in Database of abstracts of Reviews of Effects of Randomized Clinical Trials to identify eligible studies published from January 1990 to October 2021. The methodological quality of the studies was evaluated using the CONSORT list, and the Cochrane bias tool. Network meta-analysis was performed using the Bayesian random-effects model, with multivariate meta-regression to assess the association of interest. Results: 87 randomized clinical trials were identified that met the inclusion criteria, and 70 articles were included in the network meta-analysis. Regarding the methodological quality of the studies, 47 had a low or moderate bias risk. The most common adverse effects on sleep reported in the studies were insomnia, somnolence, and sedation. The results of the network meta-analysis showed that ziprasidone was associated with an increased risk of insomnia (OR, 1.56; 95% credible interval CrI, 1.18-2.06). Several of the included antipsychotics were associated with a significantly increased risk of somnolence; haloperidol (OR, 1.90; 95% CrI, 1.12-3.22), lurasidone (OR, 2.25; 95% CrI, 1.28-3.97) and ziprasidone (OR, 1.79; 95% CrI, 1.06-3.02) had the narrowest confidence intervals. In addition, perphenazine (OR, 5.33; 95% CrI, 1.92-14.83), haloperidol (OR, 2.61; 95% CrI, 1.14-5.99), and risperidone (OR, 2.41; 95% CrI, 1.21-4.80) were associated with an increased risk of sedation compared with placebo, and other antipsychotics did not differ. According to the SUCRAs for insomnia, chlorpromazine was ranked as the lowest risk of insomnia (57%), followed by clozapine (20%), while flupentixol (26 %) and perospirone (22.5%) were associated with a lower risk of somnolence. On the other hand, amisulpride (89.9%) was the safest option to reduce the risk of sedation. Discussion: Insomnia, sedation, and somnolence were the most frequent adverse effects on sleep among the different antipsychotics administered. The evidence shows that chlorpromazine, clozapine, flupentixol, perospirone, and amisulpride had favorable safety profiles. In contrast, ziprasidone, perphenazine, haloperidol, and risperidone were the least safe for sleep. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Long-acting injectable (LAI) antipsychotics (APs) each have an oral equivalent formulation, while aripiprazole, olanzapine, and ziprasidone each also have a short-acting injectable (SAI) equivalent formulation. Inpatient prescribing patterns of LAIs and their oral/SAI equivalents are less characterized in populations other than Medicaid, Medicare, and Veterans Affairs populations. Mapping out inpatient prescribing patterns remains an important first step to ensure appropriate use of antipsychotics during this critical juncture of patient care prior to discharge. This study determined inpatient prescribing patterns of first- (FGA) and second-generation antipsychotic (SGA) LAIs and their oral/SAI formulations. Methods: This was a large retrospective study using the Cerner Health Facts® database. Hospital admissions due to schizophrenia, schizoaffective disorder, or bipolar disorder from 2010 to 2016 were identified. AP utilization was defined as the proportion of inpatient stays during which at least 1 AP was administered to the total number of inpatient visits over the observed period. Descriptive analyses were used to determine prescribing patterns for APs. Chi-square tests were used to determine utilization differences across years. Results: 94,989 encounters were identified. Encounters during which oral/SAI of SGA LAIs were administered were most common (n = 38,621, 41%). Encounters during which FGA LAIs or SGA LAIs were administered were the least common (n = 1,047, 1.1%). Prescribing patterns differed across years (p < 0.05) within the SGA LAI subgroup analysis (N = 6,014). Paliperidone palmitate (63%, N = 3,799) and risperidone (31%, N = 1,859) were the most frequently administered. Paliperidone palmitate utilization increased from 30% to 72% (p < 0.001), while risperidone utilization decreased from 70% to 18% (p < 0.001). Conclusions: Compared with their oral or SAI formulations, LAIs were underutilized from 2010 to 2016. Among SGA LAIs, the prescribing patterns of paliperidone palmitate and risperidone changed significantly. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with psychotic disorders have increased rates of medical comorbidities. In this cross-sectional study, we investigated the relationship between antipsychotics and medical comorbidities among patients with psychotic disorders in an urban psychiatry clinic in Atlanta, Georgia (n = 860). Each antipsychotic group was compared to a group of patients from the same sample who were not on any antipsychotic, and logistic regression models were constructed for each comorbidity. Ziprasidone was associated with diabetes (aOR 2.56, 95% CI 1.03–6.38) and obesity (aOR 3.19, 95% CI 1.37–7.41). Aripiprazole was associated with obesity (aOR 2.39, 95% CI 1.27–4.51). Clozapine was associated with GERD (aOR 3.59, 95% CI 1.11–11.61), movement disorders (aOR 4.44, 95% CI 1.02–19.32), and arrythmias (4.89, 95% CI 1.44–16.64). Two antipsychotics that are considered weight neutral, ziprasidone and aripiprazole, were associated with cardiometabolic comorbidities. This study suggests that research is warranted to study the association between antipsychotics, medical comorbidity, and psychotic symptom burden. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Trial registration: The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn: ChiCTR-OIC-16007970. [ABSTRACT FROM AUTHOR]

Richter Geodon Vegyeszeti Gyar RT v Laboratórios Leon Farma S.A. [ABSTRACT FROM AUTHOR]

(1) Background: To systematically review evidence on the safety and efficacy of psychopharmacological treatments available for psychomotor agitation (PA) in children and adolescents. (2) Methods: Studies assessing the safety and efficacy of psychopharmacological treatments for acute PA in children and adolescents that were published between January 1984 and June 2022 on PubMed were systematically reviewed. We included: (i) papers that presented a combination of the search terms specified in the "Search strategy" sub-paragraph; (ii) manuscripts in English; (iii) original papers; (iv) prospective or retrospective/observational studies and experimental or quasi-experimental reports. The exclusion criteria were: (i) review papers; (ii) non-original studies including editorials and book reviews; (iii) studies not specifically designed and focused on the selected topic. (3) Results: We selected 42 papers: 11 case series (11/42, 26.19%), 8 chart reviews (8/42, 19.05%), 8 case reports (8/42, 19.05%), 6 double-blind placebo-controlled randomized studies (6/42, 14.29%), 4 double-blind controlled randomized studies (4/42, 9.52%), 4 open-label trials (4/42, 9.52%) and 1 case control (1/42, 2.38%). (4) Conclusions: The drugs most frequently used to treat agitation in children and adolescents were ziprasidone, risperidone, aripiprazole, olanzapine and valproic acid. Further studies are needed to evaluate the efficacy/safety ratio, considering the limited number of observations in this field. [ABSTRACT FROM AUTHOR]

A systematic study was performed into the degradation of ziprasidone in simulated postmortem blood. Fifteen potential degradation products not previously reported in the literature were observed. Four resulted from degradation in human blood, whereas the remaining products resulted from reaction with solvents: four from alkaline degradation, four from reaction with acetaldehyde, and three from reaction with acetone. To identify possible degradation products, a liquid chromatograph‐diode array detector (LC‐DAD) and liquid chromatograph quadrupole‐time‐of‐flight mass spectrometer (LC‐QTOF‐MS) operating in auto‐MS/MS mode were used. It was indicated from red‐shifted UV–Vis spectra, accurate mass data, mass fragmentation data, and a deuteration experiment that the site of ziprasidone degradation, in the in vitro blood experiments, was the methylene carbon of the oxindole moiety. The major in vitro blood degradation products were proposed to be E/Z isomers of 3‐ethylidene‐ziprasidone. Further, another in vitro degradation product in microbially inoculated blood specimens was proposed to be 3‐ethyl‐ziprasidone. 3‐Ethylidene‐ziprasidone was hypothesized to form from the reaction of ziprasidone with acetaldehyde derived from the ethanol used to spike ziprasidone into the in vitro blood experiments. Data from two postmortem investigations were available for retrospective reanalysis. Attempts were made to detect degradation products of ziprasidone, but none were found. [ABSTRACT FROM AUTHOR]

This paper reported a case of drug eruption in a male patient with first-episode schizophrenia. The patient received ziprasidone monotherapy， and experienced post-treatment remission of schizophrenic symptoms， while accompanied by drug eruption with fever and elevated white blood cell count. Even with antiallergic treatment， the eruption did not subside without discontinuation of ziprasidone， whereas the eruption resolved after discontinuation of ziprasidone. This case suggested that individual allergy history should be taken into account during the use of ziprasidone， and timely intervention of adverse skin reactions was essential to prevent the development of severe drug eruption.

This paper reported a case of a 25-year-old male schizophrenic patient， who obtained remission from psychotic symptoms during the treatment of olanzapine and trihexylphenidyl， was given ziprasidone treatment additionally due to the occurrence of auditory hallucination， and developed stuttering 4 days later. The stuttering disappeared 2 days following the discontinuation of therapy， and reappeared after reinstitution of ziprasidone therapy， but disappeared again after discontinuation. The dose of olanzapine was increased to 20 mg/d to ensure the stability of psychotic remission. At a follow-up visit 4 months later， the patient’s mental condition was stable and stuttering did not recur， indicating that the stuttering was induced by ziprasidone. This case suggests that the possibility of stuttering as an adverse reaction should be considered in the clinical application of ziprasidone.

Rationale : While meta-analyses of clinical trials found that lurasidone and partial dopamine agonists (brexpiprazole and aripiprazole) were the antipsychotics less likely to cause QTc prolongation, and sertindole, amisulpride, and ziprasidone were the most frequently associated with this adverse drug reaction; no real-world studies have investigated this risk between the different antipsychotics. Objectives and methods: Using data recorded from 1967 to 2019 in VigiBase®, the World Health Organization's Global Individual Case Safety Reports database, we performed disproportionality analysis to investigate the risk of reporting QT prolongation between 20 antipsychotics. Results: Sertindole had the highest risk of reporting QT prolongation, followed by ziprasidone and amisulpride. Lurasidone was associated with the lowest risk. First-generation antipsychotics were associated with a greater QT prolongation reporting risk (ROR, 1.21; 95%CI, 1.10–1.33) than second-generation antipsychotics. A positive correlation was found between the risk of reporting QT prolongation and affinity for hERG channel (R2 = 0.14, slope = Pearson coefficient = 0.41, p value = 0.1945). Conclusions: This large study in a real-world setting suggests that sertindole and ziprasidone were the antipsychotics drugs associated with the highest risk of QT prolongation reporting. Our results suggest that lurasidone is less associated with QT interval prolongation reports. Our study also suggests that antipsychotics with the higher hERG affinity are more associated with to QT prolongations reports. [ABSTRACT FROM AUTHOR]

Vesicular monoamine transporter 2 (VMAT2) is responsible for packing monoamine neurotransmitters into synaptic vesicles for storage and subsequent neurotransmission. VMAT2 inhibitors are approved for symptomatic treatment of tardive dyskinesia and Huntington's chorea, but despite being much-studied inhibitors their exact binding site and mechanism behind binding and inhibition of monoamine transport are not known. Here we report the identification of several approved drugs, notably β2-adrenergic agonists salmeterol, vilanterol and formoterol, β2-adrenergic antagonist carvedilol and the atypical antipsychotic ziprasidone as inhibitors of rat VMAT2. Further, plausible binding modes of the established VMAT2 inhibitors reserpine and tetrabenazine and hit compounds salmeterol and ziprasidone were identified using molecular dynamics simulations and functional assays using VMAT2 wild-type and mutants. Our findings show VMAT2 as a potential off-target of treatments with several approved drugs in use today and can also provide important first steps in both drug repurposing and therapy development targeting VMAT2 function. Several existing β2-adrenergic agonists and antagonists, as well as the atypical antipsychotic ziprasidone, are identified as high affinity VMAT2 inhibitors, which could have implications for drug repurposing and drug derivatization campaigns. [ABSTRACT FROM AUTHOR]

Background: Ziprasidone is a second-generation antipsychotic drug commonly used to treat schizophrenia and bipolar disorder. Acne is a common inflammatory disease of sebaceous glands in adolescents that is often co-morbid with anxiety and depression, which may reduce treatment compliance. Through unknown mechanisms, ziprasidone may cause a range of inflammatory responses. Whether ziprasidone can cause acne in young patients with bipolar disorder has not been reported. Case summary: We report a 23-year-old woman with a 5-year history of bipolar disorder who experienced acne during use of ziprasidone. She was admitted to our hospital during 1-month aggravation of her symptoms and was diagnosed with bipolar I disorder (current or most recent episode of depression) with psychotic features. She was given ziprasidone and soon developed acne, which she never had before; the rash worsened substantially when the ziprasidone dose was increased. At the same time, levels of inflammatory factors increased. The rash resolved after ziprasidone therapy was stopped. Conclusion: When prescribing ziprasidone to young people with bipolar disorder, clinicians should consider the potential for adverse skin reactions. It may be useful to assay levels of inflammatory markers during ziprasidone therapy and adjust the dose if necessary in order to ensure treatment compliance. [ABSTRACT FROM AUTHOR]