Acute Schizophrenia Research Articles

Cost Analysis of Antipsychotics Schizophrenia of Inpatients in Mental Hospital West Java Province

Schizophrenia is a mental disorder that can affect behavior, emotions and communication. In the agitation phase ithe patient is acompanied by destructive or violent behavior. In these conditions, the patient must immediately calm down to avoid risk. Monotherapy Treatment in acute agitation schizophrenia is recommended than combination therapy. The purpose of this study was to determine the effectiveness of treatment costs and the factors that influence the total cost of schizophrenia patients at the Mental Hospital of West Java Province. This study was observational by cross sectional study design according to the hospital perspective. This method is retrospective data. The subject were inpatients aged 18-65 years with diagnosis of schizophrenia disorder and receiving antipsychotic therapy for at least 1 month. The results showed that average cost-effectiveness ratio (ACER) Rp.288.659/ 1 score PANSS EC with an average decrease score of 9,70. There is a difference in variant data compared because p-value = 0.011<0,05. ICER calculation of A to C = (Rp. 2.800.001–Rp. 2.593.821) / (9.70 - 8.57) = Rp. 182.460. The factors that influence the total cost found that the most significant are administration and room. The conclusion is atypical-atypical monotherapy recommended as a treatment for schizophrenic in agitation acute.

Intestinal infectious diseases increase the risk of psychiatric disorders: A nationwide population-based cohort study.

Intestinal infectious diseases (IIDs) are among the most common diseases and are prevalent worldwide. IIDs are also one of the major disease groups with the highest incidence worldwide, especially among children and older adults. We observed a higher probability of IIDs in patients from the psychiatric department of Tri-Service General Hospital. Therefore, our objective was to investigate if there is an association between IIDs and the risk of developing psychiatric disorders. This nationwide population-based study used the database of the National Health Insurance (NHI) program in Taiwan. The study included 150,995 patients from 2000 to 2015, comprising 30,199 patients with IIDs as the study group and 120,796 patients without IIDs as the control group. Cox proportional hazards regression analysis was performed to calculate the hazard ratio of psychiatric disorders during the 16-year follow-up. Of the patients with IIDs, 4022 (13.32%) developed psychiatric disorders compared to 8119 (6.72%) who did not (P < .001). The adjusted hazard ratio (aHR) for overall psychiatric disorders in the study group was 2.724 (95% confidence interval [CI]: 2.482–2.976; P < .001). More specifically, the study group had a higher risk of developing a psychiatric disorder, including sleep disorders, depression, anxiety, bipolar disorder, post-traumatic stress disorder (PTSD)/acute stress disorder (ASD), schizophrenia, mental retardation (MR), substance abuse, and other psychiatric disorders. Furthermore, refractory IIDs (seeking medical attention for IIDs 3 or more times) increased the risk (aHR: 3.918; 95% CI: 3.569–4.280; P < .001) of developing psychiatric disorders. There was an association between IIDs and the increased risk of developing psychiatric disorders. The novel role of etiological factors in the development of psychiatric disorders deserves more attention, and the control of pathogens that cause IIDs is of urgent public health importance.

Immunoglobulins G of Patients with Schizophrenia Protects from Superoxide: Pilot Results.

This study aimed to evaluate the superoxide dismutase (SOD) activity of IgG in patients with schizophrenia. After signing informed consent, we included 67 patients with schizophrenia (34 people with acute schizophrenia and 33 individuals were on outpatient treatment in therapeutic remission) and 14 healthy volunteers. IgGs from blood serum were isolated by affinity chromatography. SOD activity of antibodies was determined spectrophotometrically. We have shown for the first time that IgGs from patients with schizophrenia have SOD activity and this activity is an intrinsic property of antibodies. The maximum increase in SOD activity was registered in the group of patients in therapeutic remission compared with acute schizophrenia (p = 0.005) and in healthy individuals (p = 0.001). Based on the data of inhibitory analysis using a specific SOD inhibitor enzyme, triethylenetetramine (TETA), we can assume that the mechanism of the SOD activity of IgG is similar to the mechanism of classical enzyme catalysis. According to the kinetic analysis, the affinity of the IgGs to the substrate is higher than that of the classical SOD enzyme.

Personalized approach to early diagnosis of acute schizophrenia: an observational comparative study

BACKGROUND: An acute schizophrenic episode often meets the diagnostic criteria for the ICD-10 category acute and transient psychotic disorders (ATPD, F23), which includes clinically similar conditions of diverse etiologies. The presence of schizophrenic negative symptoms in ATPD signifies their nosological affiliation and determines the therapeutic tactics. Early recognition of the schizophrenic etiology in the first episode of psychosis may contribute to the development of a personalized approach for the management of patients with acute psychotic disorders.&#x0D; AIM: To evaluate the relationship between the developmental characteristics of psychosis and identify the negative symptoms after its reduction in patients with ATPD with the symptoms of schizophrenia.&#x0D; MATERIALS AND METHODS: This observational single-center selective comparative study was conducted during 20182020. The clinical-psychopathological method was applied to examine patients hospitalized in a psychiatric hospital with ATPD presenting with the symptoms of schizophrenia (F23.1). In order to objectify the results of the study, the positive and negative syndrome scale was used.&#x0D; RESULTS: The study involved 60 patients (50 men, 10 women) aged 1846 years (mean age: 21.46.0 years). Depending on the presence of negative symptoms after the psychosis reduction at 4 weeks of therapy, the study sample was divided into two groups: 1) the group with negative symptoms (NS+; n=41); 2) the group without any negative symptoms (NS; n=19). Individuals presenting with negative symptoms were distinguished from those without it based on the more frequent presence of prodromal disorders, subpsychotic, and, particularly, mild negative disorders at the prodromal stage, prolonged development, and long-drawn course of psychosis. The likelihood of negative symptoms detection after the reduction of psychosis was associated with a family history of schizophrenia and other psychiatric disorders, low premorbid social adjustment, prodromal symptoms, and impaired functioning, as well as with a longer duration of psychotic symptoms and its slow development.&#x0D; CONCLUSION: The likelihood of negative symptoms after the reduction of ATPD with symptoms of schizophrenia was associated with hereditary and premorbid characteristics of patients, prodromal psychopathological and functional abnormalities, as well as the clinical and dynamic characteristics of psychosis. The data obtained from this study may contribute to the early recognition of schizophrenia-spectrum disorders and to the development of a personalized approach for the management of patients with ATPD.

Cariprazine (Vraylar)

&#x0D; CADTH recommends that Vraylar should not be reimbursed by public drug plans for the treatment of schizophrenia in adults.&#x0D; Based on evidence from 5 clinical trials, treatment with Vraylar improved symptoms of schizophrenia or delayed relapse compared with placebo. Vraylar also improved negative symptoms of schizophrenia compared with risperidone. Although these results were statistically significant, it is not clear whether any of these effects are clinically important.&#x0D; It is not clear whether cariprazine offers any clinical benefits over other treatments that are available for schizophrenia because there were no clinical trials in patients with acute schizophrenia that compared Vraylar with any other treatments. The committee did not have confidence in the results because the indirect comparative evidence reviewed had too many limitations.&#x0D; There was not enough evidence to show that Vraylar filled a treatment gap.&#x0D;

Efficacy and Safety of Low-Dose Brexpiprazole for Acute Schizophrenia: Meta-Analysis of Randomized Placebo-Controlled Trials.

PurposeThe purpose of this meta-analysis was to compare the efficacy and safety profile of low-dose brexpiprazole (<2 mg/d) compared to placebo and standard-dose brexpiprazole (2–4 mg/d).Patients and MethodsWe identified relevant studies pertaining to the specific purpose of our meta-analysis by searching PubMed, Web of Science, Embase, Cochrane library, and PsycINFO using the search terms “schizophrenia” or “schizophrenic” AND “brexpiprazole” or “REXULTI”. We systematically reviewed all randomized controlled trials (RCTs) comparing low-dose brexpiprazole with placebo. Primary efficacy outcomes were the PANSS total score change and response rate. Primary safety outcomes were total treatment discontinuation rate, and total serious adverse events (SAEs). Risk ratios (RR) and standardized mean differences (SMDs) were pooled implementing a random effect model.ResultsFour RCTs (2178 patients) were included for effect assessment of low-dose brexpiprazole treatment on the patients with acute schizophrenia. Low-dose brexpiprazole was not superior to placebo (SMD = −0.11, 95% CI = −0.23, 0.02, P = 0.10, I2 = 0%), and significantly inferior to standard-dose brexpiprazole (SMD = 0.15, 95% CI = 0.03, 0.26, P = 0.01, I2 = 0%) for PANSS total score change. Low-dose brexpiprazole did not result in significant difference for response rate when compared to placebo and standard-dose brexpiprazole (RR = 1.16, 95% CI = 0.95, 1.41, P = 0.14, I2 = 25%; RR = 0.92, 95% CI = 0.76, 1.12, P = 0.40, I2 = 38%, respectively). For ratio of total discontinuation, low-dose brexpiprazole did not exhibit significant difference when compared to placebo (RR = 0.95, 95% CI = 0.81, 1.11, P = 0.53, I2 = 0%) and standard-dose brexpiprazole group (RR = 1.11, 95% CI = 0.95, 1.29, P = 0.19, I2 = 0%). Total SAEs in low-dose brexpiprazole group did not differ significantly from placebo and standard-dose brexpiprazole group (RR = 0.96, 95% CI = 0.52, 1.80, P = 0.90, I2 = 0%; RR = 1.29, 95% CI = 0.65, 2.57, P = 0.47, I2 = 26%, respectively).ConclusionThe results indicated that low-dose brexpiprazole may be not superior for improving the efficacy and safety for acute schizophrenia compared to placebo and standard-dose brexpiprazole, and may cause additional risk of increasing body weight. Therefore, using low-dose brexpiprazole in acute schizophrenia patients may be not recommended.

A clinical review: schizophrenia, transsexualism or their combination?

The change in the position of transsexualism in the new ICD classification, the hot debate about the psychopathological structure of this phenomenon and its relation to other mental disorders determine the relevance of considering the following clinical case.A detailed clinical description demonstrates the possibility of combining two initially independent disorders - transsexualism and schizophrenia - which gave a bright individual color to the clinical picture and caused difficulties both in the medical and legal aspects of patient care.At the age of 25, a patient with clinical signs of transsexualism developed acute paraphrenia psychosis. Without medical assistance, according to the mechanisms of sanogenesis, the severity of the condition decreased, but the psychotic state was not recovered. Features of the onset and dynamics of psychosis typical for the continuous type of paranoid schizophrenia (acuteness of development and absence of signs of syndromotaxis) allow us to attribute it to episodic with progressive or stable deficit paranoid schizophrenia variant. It is noteworthy that after the onset of psychosis, the stereotype of the development of birth-assigned gender rejection syndrome did not undergo significant changes: the formation of crossdressing, inverse psychosexual identity and inverse gender identity were finally completed; mimicry reactions became bright, self-destructive tendencies began to appear more and more clearly, and the patient applied for permission to change gender.In the described clinical situation, the primary task is to overcome the acute schizophrenia psychosis. After solving this problem, the secondary prevention and rehabilitation program development becomes more important. Formally, the patient does not have the right to change sex, since she suffers from schizophrenia, which is a contraindication for sex transformation. In the state of psychosis, the patient essentially loses her civil procedural capacity. Informally, the question remains relevant.

Benzodiazepine use during cariprazine treatment in acute schizophrenia

IntroductionAlthough antipsychotics are first-line treatments for schizophrenia, benzodiazepines (BZDs) are often used as concomitant medications in acutely exacerbated patients due to their anxiolytic and sedative effects. Cariprazine (CAR), a D3-preferring dopamine D2/D3 partial agonist antipsychotic, has been examined in many clinical studies for the treatment of acute schizophrenia, with and without benzodiazepines.ObjectivesTo delineate the effects of benzodiazepine-use during cariprazine treatment in acute schizophrenia.MethodsPooled data of cariprazine-treated (1.5-6mg/day) and placebo-treated patients from four short-term, randomised, double-blind trials (NCT00404573, NCT01104766, NCT01104779, NCT00694707) were analysed. Baseline characteristics (age, duration of illness) and efficacy outcome parameters (Total and Hostility Factor Score of the Positive and Negative Syndrome Scale [PANSS]) were compared in patients receiving benzodiazepines (for more ≥3 consecutive days) and not receiving benzodiazepines (&lt;3 consecutive days).ResultsAltogether, 36.7% and 40.7% of the CAR-treated and PBO-treated patients required BZDs. BZD-taking was associated with a higher age in both the CAR-treated (p=0.0002) and PBO-treated (p&lt;0.0001) patients, and with longer illness-duration in both treatment groups (p&lt;0.0001). PANSS Total Score at baseline was similar for BZD users and non-users (CAR: LS Mean=96.36 and 96.27; PBO: LS Mean=95.55 and 96.66). Change from baseline in the PANSS Total Score was greater for patients who did not use BZD vs those who did (CAR: LS Mean= -23.8 vs LS Mean 17.2, p&lt;0.0001; PBO: LS Mean= -14.0 vs LS Mean 12.9, p=0.5776).ConclusionsThese findings may suggest that requiring benzodiazepines is a potential indicator of longer illness duration and poorer response in acute schizophrenia.DisclosureI am an employee of Gedeon Richter Plc.

Superoxide dismutase activity of serum IgG in acute illness and remission period of schizophrenia

IntroductionAccording to recent research violations of the oxidative-antioxidant balance may play an important role in the pathogenesis of schizophrenia, by changing generate, conduct and reproduce a nerve impulse. Antibodies with oxidoreductase activity may be involved in protection against oxidative stress in schizophrenia.ObjectivesThe study was to compare the superoxide dismutase (SOD) activity of IgG in patients with acute schizophrenia and during remission.MethodsThe study included 20 patients with acute schizophrenia (mean PANSS total score 94,3±14), 18 people with schizophrenia during remission (mean PANSS total score 54,7±9), and 10 healthy individuals. All participants signed informed consent for the research. Isolation of IgG from blood serum was performed using affinity chromatography on Protein-G-Sepharose columns. The homogeneity of the substances is confirmed by the SDS PAGE method. SOD activity of IgG was carried out spectrophotometrically. Statistical processing was conducted with Statistica v.10.ResultsIgG of schizophrenia patients and healthy individuals have a SOD activity and studied activity is proved to be antibodies intrinsic property. The activity of antibodies in acute schizophrenia was 1.7 times higher than in healthy individuals (p&lt;0.05). In patients with schizophrenia during remission SOD activity of IgG was 2.4 times higher than in healthy individuals (p&lt;0.05).ConclusionsWe can assume that in the conditions of oppression antioxidant activity in schizophrenia patients, antibodies partially take over the function of protecting the body from patients with generalized oxidative stress. This work is supported by the Russian Scientific Foundation, grant # 18-15-00053P.DisclosureNo significant relationships.

Aripiprazole lai two-injection start in a 16 year-old with Schizophrenia

IntroductionAripiprazole LAI is approved for the treatment of schizophrenia in adults. Recently, Europe and Canada approved the use of the two-injection start (TIS) regimen: two separate injections of 400 mg long-acting aripiprazole along with a single 20 mg dose of oral aripiprazole. Aripiprazole showed efficacy in the treatment of adolescents with acute schizophrenia in several controlled trials, leading to its approval for 13-17 year-old adolescents with schizophrenia by the EMA. However, the LAI formulation still remains off-label in adolescents.ObjectivesTo demonstrate the efficacy and safety of the TIS regimen of aripiprazole LAI formulation in a 16 year-old adolescent with schizophrenia.MethodsWe evaluated the symptoms of schizophrenia and general severity by means of the PANSS and CGI scales. The scales were administered at hospital admission, after 3 weeks, 5 weeks, and at 4-weeks follow-up.ResultsAt the admission the patient PANSS total score was 136, the CGI score of 7. Aripiprazole was started and up-titrated to 30 mg/day. After 3 weeks, the positive symptoms were significantly reduced; due to the persistence of negative symptoms, clozapine 100 mg/day was added. At week 5 the PANSS total score decreased to 81. Due to poor insight we proposed aripiprazole LAI with the two-injection start. One month later, global functioning and illness insight improved; PANSS score was 43, CGI score 2. There was no evidence of akathisia or other side effects.ConclusionsAripiprazole LAI showed good efficacy and tolerability in an adolescent with schizophrenia. The two-injection start regimen was a safe and viable option.DisclosureNo significant relationships.

A DVLA Notification Audit in Forensic Supported Accommodation

AimsThe Driver and Vehicle Licensing Agency (DVLA) in England, Scotland and Wales are legally responsible for deciding if a person is medically unfit to drive. This means they need to know if a person holding a driving licence has a condition or is undergoing treatment that may now, or in the future, affect their safety as a driver. The driver is legally responsible for telling the DVLA about any such condition or treatment. Doctors should therefore alert patients to conditions and treatments that might affect their ability to drive and remind them of their duty to tell the appropriate agency. Patients with acute schizophrenia or an acute psychotic disorder must not drive and must notify the DVLA. In alliance with the above, the GMC advises that clinicians have a responsibility to explain the above information to the patient and inform them that they have a legal duty to inform the DVLA. Doctors should also inform patients that relevant medical information may need disclosing about them to the DVLA if they continue to drive against advice, and any advice given should be documented. The main objective of this audit is to identify if notification of DVLA for forensic patients living in supported accommodation, is in accordance with the DVLA guidelines.MethodsA total of 12 residents living in community forensic supported accommodation who have a notifiable diagnosis were included. Data collection took place in September 2021, looking through all previous records relating to the search words “DVLA”, “drive”, “driving” and “license”. Data audited were from the trust's electronic patient records.ResultsDiagnoses included paranoid schizophrenia, delusional disorder and personality disorder. Antipsychotic medications included Olanzapine (oral and IM), Clozapine and Zuclopenthixol +/- antidepressants. Legal status included community treatment orders (civil section), voluntary community patients and those on a conditionally discharged restriction under secretary of State supervision. Two patients held full driving licences and a further two held provisional licences, with DVLA documented discussions and notification compliance at 100%. The remaining eight patients had no documentation regarding driving nor DVLA discussions or notification.ConclusionThis audit found that DVLA discussions are not currently well documented, with only four patient records that have this recorded. Although it is the clinical team's responsibility to advise the patient to notify the DVLA, it is ultimately the patient's responsibility to notify the DVLA themselves. DVLA discussions need to be had regardless of driving status and documentation should reflect this.

The efficacy of cariprazine in chronic schizophrenia – post hoc analyses of phase II/III clinical trials

IntroductionChronic schizophrenia patients are experiencing persistent and severe illness for more than 15-20 years and are usually suffering from long-term negative symptoms. Cariprazine, a novel D3-D2 partial agonist has been proven to be effective in the treatment of acute schizophrenia, however its ability to treat chronic patients has not been assessed yet.ObjectivesThe primary aim of the present post-hoc analysis is to assess the efficacy of cariprazine in treating patients with chronic schizophrenia (late-stage and residual schizophrenia patients).MethodsData from 3 phase II/III 6-week, randomized, double-blind, placebo-controlled trials with similar design in patients with acute exacerbation of schizophrenia were pooled and patients with more than 15 years of schizophrenia were analysed (late-stage patients). Furthermore, schizophrenia patients experiencing predominantly negative symptoms from a 26-week, randomized, double-blind, active-controlled, fixed-flexible-dose trial with an ICD-10 code of F20.5 were analysed post-hoc (residual patients).ResultsAltogether, 414 late stage (286 cariprazine and 128 placebo) and 35 residual (23 cariprazine and 12 risperidone) patients were identified. The pooled analysis evaluating mean change from baseline to week 6 in the PANSS total score indicated statistically significant difference in favour of cariprazine in the late stage (LSMD -6.7, p&lt;0.01) subpopulation compared to placebo. The mean change from baseline in patients with residual schizophrenia in the cariprazine arm was -9.6 on the PANSS-FSNS scale, while -7.9 in the risperidone arm.ConclusionsBased on the results, it seems that cariprazine might be a good treatment option for patients with chronic schizophrenia. Nonetheless, further studies are needed to confirm this.DisclosureI am an employee of Gedeon Richter Plc.

Clinical predictors of kynurenine pathway aberrations in schizophrenia and bipolar disorder

IntroductionSchizophrenia and bipolar disorder are severe mental illnesses that are known to have a considerable overlap in underlying pathophysiological mechanisms. More specifically, disturbances in the kynurenine pathway have been hypothesized as processes bridging altered immune responses and clinical manifestations of these illnesses.ObjectivesThe aim of this study was to investigate the abnormalities in serum kynurenine metabolites in schizophrenic and bipolar patients and the impact of clinical factors.MethodsFour patient groups were included in the current study: 1) Acute bipolar inpatients (n=205); 2) stable bipolar outpatients (n=116); 3) acute schizophrenia inpatients (n=111) and 4) stable schizophrenia outpatients (n=75); and one healthy control group (n=185). Clinical symptoms were established using symptom severity scales. The quantitative determination of serum kynurenine metabolites was performed using LC-MS/MS. General linear model and multivariate linear regression analyses were used to perform the statistical analysis with JMP Pro 15.ResultsIn line with previous research, the results indicate that serum kynurenine metabolites are disturbed in schizophrenic and bipolar patients compared to healthy controls. Whereas no differences were observed between schizophrenia and bipolar disorder, illness state and duration of illness clearly impacted kynurenine metabolite levels. Acutely ill patients had significantly lower levels compared to stable patients, which seemed to be driven by psychotic symptoms.ConclusionsTo conclude, the results confirm the involvement of the kynurenine pathway in the pathophysiology of schizophrenia and bipolar disorder by lowered peripheral kynurenine metabolite level. In addition, an important role of acute psychotic symptoms and longer illness duration on these metabolite aberrances is demonstrated.DisclosureNo significant relationships.

Enhancement of Haloperidol Binding Affinity to Dopamine Receptor via Forming a Charge-Transfer Complex with Picric Acid and 7,7,8,8-Tetracyanoquinodimethane for Improvement of the Antipsychotic Efficacy.

Haloperidol (HPL) is a typical antipsychotic drug used to treat acute psychotic conditions, delirium, and schizophrenia. Solid charge transfer (CT) products of HPL with 7,7,8,8-tetracyanoquinodimethane (TCNQ) and picric acid (PA) have not been reported till date. Therefore, we conducted this study to investigate the donor–acceptor CT interactions between HPL (donor) and TCNQ and PA (π-acceptors) in liquid and solid states. The complete spectroscopic and analytical analyses deduced that the stoichiometry of these synthesized complexes was 1:1 molar ratio. Molecular docking calculations were performed for HPL as a donor and the resulting CT complexes with TCNQ and PA as acceptors with two protein receptors, serotonin and dopamine, to study the comparative interactions among them, as they are important neurotransmitters that play a large role in mental health. A molecular dynamics simulation was ran for 100 ns with the output from AutoDock Vina to refine docking results and better examine the molecular processes of receptor–ligand interactions. When compared to the reactant donor, the CT complex [(HPL)(TCNQ)] interacted with serotonin and dopamine more efficiently than HPL only. CT complex [(HPL)(TCNQ)] with dopamine (CTtD) showed the greatest binding energy value among all. Additionally, CTtD complex established more a stable interaction with dopamine than HPL–dopamine.

Comparison of Efficacy and Safety Between Low-Dose Ziprasidone in Combination With Sertraline and Ziprasidone Monotherapy for Treatment-Resistant Patients With Acute Exacerbation Schizophrenia: A Randomized Controlled Trial.

Treatment-resistant schizophrenia (TRS) is a prevalent clinical problem with heterogeneous presentations. However, the clinical trial designs for new treatments are still lacking. This study aimed to assess the efficacy of ziprasidone plus sertraline in TRS patients as compared to ziprasidone monotherapy. We conducted a 24 weeks, randomized, controlled, double-blinded clinical research trial. 62 treatment-resistant patients with acute exacerbation SZ were randomly allocated to receive a usual dose of ziprasidone (120–160 mg/d) monotherapy (Control group) and 53 TRS inpatients were to receive a low dose of ziprasidone (60–80 mg/d) in combination with sertraline (ZS group). Treatment outcomes were measured by the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and Personal and Social Performance Scale (PSP) at baseline, week 4, 8, 12, and 24. Relative to control group, the patients in ZS group showed greater reductions in the following: PANSS positive symptom, negative symptom, total score, and HAMD total score. Additionally, the patients in ZS group had a greater increase in PSP total score. Notably, the reduction in HAMD was positively correlated with the reduction in PANSS total score. The reduction in CGI-S was a predictor for the improvement of psychosocial functioning in patients. Furthermore, the ZS group had a lower rate of side effects compared to the control group. Our findings suggest that a low dose of ziprasidone in combination with sertraline is an effective therapy for the clinical symptoms as compared to a usual dose of ziprasidone in the treatment-resistant patients with acute exacerbation SZ. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04076371.

Elevated Serum Purine Levels in Schizophrenia: A Reverse Translational Study to Identify Novel Inflammatory Biomarkers.

BackgroundImmunological markers and related signaling molecules in the blood are altered in schizophrenia mouse models, in acutely relapsed patients with schizophrenia, and in persons at a clinically high risk for subsequently developing psychosis, highlighting their potential as prognostic and theranostic biomarkers. Therefore, we herein aimed to identify novel potential biomarkers in the serum that are associated with purinergic signaling.MethodsTo our knowledge, this is the first study to assess the correlations among the levels of human serum adenine nucleotides (ATP, ADP), adenosine, P2X7 receptor, and disease activity in patients hospitalized due to an acute relapse of schizophrenia (n = 53) and healthy controls (n = 47). In addition, to validate these findings using a reverse translational approach, we examined the same parameters in an acute phencyclidine-induced schizophrenia mouse model.ResultsWe found consistently elevated levels of ATP, ADP, interleukin (IL)-6, and IL-10 in both schizophrenia groups compared with the controls. The levels of adenosine, IL-1β, IL-12, and C-reactive protein were also increased in the human patient samples. Moreover, ATP and ADP were significantly positively correlated with the Positive and Negative Symptom Scale item “lack of judgment and insight”; IL-1β, IL-12, and tumour necrosis factor alpha were significantly positively correlated with “tension” and “depression”; and “disorientation” and “poor attention” were correlated significantly with IL-6 and IL-8.ConclusionsOur study suggests the promising potential of blood purines and inflammatory markers as future prognostic tools.

Fast In Vitro Release and In Vivo Absorption of an Anti-Schizophrenic Drug Paliperidone from Its Soluplus®/TPGS Mixed Micelles.

The purpose of this study was to develop a drug delivery system for paliperidone (PPD) in order to provide a more effective therapeutic strategy for patients with acute schizophrenia. PPD-loaded Soluplus®/TPGS mixed micelles (PPD-S/T-MM) were prepared using the thin-film hydration method. The critical micelle concentration (CMC) of blank S/T-MM was 4.77 × 10−2 mg/mL. PPD presented much higher solubility in PPD-S/T-MM formulation than that in pure water. The particle size of blank or drug loaded S/T-MM was around 60 nm. The polydispersity index (PDI) was less than 0.1. PPD-S/T-MM presented a nearly spherical shape under transmission electron microscopy. The encapsulation efficiency (EE%) of PPD-S/T-MM was higher than 94%. Based on the analysis of XRD and DSC, it was proved that PPD was incorporated in the core of the mixed micelles as amorphous dispersion or solid solution. PPD-S/T-MM were stable when they were undergoing dilution with water and the change of environmental pH. Although PPD-S/T-MM showed lower rates to release PPD than those from PPD raw material in acidic solution, they provided faster release rates in neutral conditions than those from PPD raw material who only showed modest dissolution in the same neutral condition. This proves that PPD-S/T-MM can release PPD in a more controlled manner. After oral administration of PPD-S/T-MM (dose of PPD, 6 mg/kg) in rats, the plasma concentration of PPD increased rapidly: Tmax was 0.83 ± 0.29 h, and Cmax was 844.33 ± 93.73 ng/mL. Oral administration of PPD suspension resulted in longer Tmax and lower Cmax. The relative oral bioavailability was about 158% for PPD-S/T-MM over PPD suspension. These findings confirm that PPD-S/T-MM can provide faster release in neutral conditions and better oral absorption in rats than those from PPD raw material, which should potentially benefit patients with acute schizophrenia.

Relation Between Unconjugated Bilirubin and Peripheral Biomarkers of Inflammation Derived From Complete Blood Counts in Patients With Acute Stage of Schizophrenia.

BackgroundInflammation and oxidative stress are the major leading hypothetical causes of schizophrenia. Unconjugated bilirubin (UCB) is an efficient endogenous plasma antioxidant. Inflammation is closely linked to oxidative stress. The relationship between UCB and inflammatory markers should be paid close attention in schizophrenia acute stage. In this paper, combined UCB and inflammatory markers were evaluated for their capability in predicting schizophrenia in the acute stage to find an easy and effective indicator to identify acute schizophrenia.MethodsA total of 6,937 acute schizophrenia patients and 6,404 healthy controls (HCs) were enrolled. UCB and peripheral biomarkers of inflammation derived from complete blood counts (CBC) were investigated in the subjects with acute schizophrenia, and the results were compared with HCs. Simultaneously, Spearman test was employed to assess the correlation between the variables, while logistic regression was adopted to determine the combined equation and receiver operating characteristic curve was used to evaluate the combined value of UCB and peripheral biomarkers of inflammation derived from CBC to predict schizophrenia in the acute stage.ResultsThe study indicates that white blood cells, neutrophil, monocyte, mean platelet volume (MPV), red cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR) have significantly increased in schizophrenia (p < 0.05 for all), while platelet, lymphocyte, and platelet/lymphocyte ratio (PLR) in schizophrenia have significantly decreased (p < 0.05 for all). UCB exhibits negative correlation with MPV significantly (r = 0.121, p < 0.001), and no correlation with neutrophil and monocyte. The correlations between UCB and other peripheral biomarkers of inflammation derived from CBC are very weak. MPV, RDW, NLR, MLR, PLR, and UCB were taken as independent variables for a logistic regression analysis. The model was as follows: Logit (P1)=-6.141+0.827 MPV+5.613 MLR-0.005 PLR-0.346 UBC. The combination demonstrates better effectiveness in predicting schizophrenia in the acute stage (AUC 0.831, 95% CI 0.825 to 0.837).ConclusionUCB has a protective effect on acute stage of schizophrenia, which is weak and indirect by affecting the proinflammatory processes. Our findings suggest that a combination of MLR, MPV, PLR, and UBC could be used to predict acute stage of schizophrenia.

Changes in leukocytes and CRP in different stages of major depression

BackgroundWe recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD).MethodsWe assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6).ResultsConsidering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0–T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients.ConclusionsThese findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.

Thermodynamic analysis and molecular dynamic simulation of the solubility of risperidone (form I) in the pure and binary solvents

Risperidone is one of the second-generation anti-schizophrenia representative drugs, which is widely used in the treatment of acute and chronic schizophrenia. In this work, the solubility of risperidone (form I) in thirteen pure solvents and three binary solvent mixtures (ethanol + water, acetone + water and 2-propanol + water) was determined. The measured temperature range was 278.15–313.15 K and the measurement was accomplished by utilizing a gravimetric method under the barometric pressure. The experimental solubility data were correlated by the Apelblat equation, λh equation, NRTL model, UNIQUAC model, Jouyban-Acree model and CNIBS/R-K model with all the calculated solubility data dovetailing well with the experimental solubility data. The solubility of risperidone (form Ⅰ) in selected solvent systems was positively correlated with the temperature and the co-solvency phenomenon was observed in all the three binary solvent systems, which was different from the results obtained from the literature. The Hirshfeld surface (HS) analysis was applied to understand the intermolecular interaction of the crystal packing of risperidone (form I). The molecular dynamic simulation was then carried out and the Radial distribution function (RDF) analysis was employed to illustrate the intermolecular interaction between the solute and solvent molecules, and it turns out that the results of the RDF analysis can well explain the co-solvency phenomenon. In addition, based on the van’t Hoff equation, the apparent thermodynamic properties of risperidone (form I) in selected solvent systems were calculated and the results show that the dissolution of risperidone (form I) is a process of endothermic and entropy-driven.