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Background: The nature of aberrant salience in schizophrenia, whether it is a state or a trait phenomenon, remains unclear. Aim: To assess and compare aberrant salience in patients with schizophrenia at different stages of the illness and to explore its association with symptom severity and medication use. Methods: A total of 113 subjects were included, comprising 83 patients with schizophrenia divided into three groups: group A (acute drug-free symptomatic stage, n = 23), group B (chronic-medicated symptomatic stage, n = 30), and group C (chronic-medicated asymptomatic stage, n = 30). These were compared with a healthy control group (group D, n = 30). Participants were assessed using the Aberrant Salience Inventory (ASI) and clinical rating scales, including Psychotic Symptom Rating Scales, Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms (SANS). Results: Significant differences were observed across almost all domains of aberrant salience. The most notable differences were between the symptomatic groups (A, B) and the healthy controls (D). Subgroup analysis showed no significant differences between the acute (A) and chronic groups (B, C), but significant differences were found between the symptomatic (A, B) and asymptomatic (C) groups in several domains and in the total ASI score. A highly significant positive correlation was noted between the total ASI score and the symptom rating scales, except for SANS. Conclusion: Aberrant salience is significantly elevated in patients with prominent positive symptoms, particularly delusions and hallucinations. It appears comparable to the general population in chronic remitted patients, suggesting that aberrant salience is state-dependent. Medication did not significantly influence aberrant salience as both medicated and nonmedicated symptomatic patients continued to exhibit it. However, medication may contribute to reducing aberrant salience by alleviating positive psychotic symptoms. [ABSTRACT FROM AUTHOR]

Background: The nature of aberrant salience in schizophrenia, whether it is a state or a trait phenomenon, remains unclear. Aim: To assess and compare aberrant salience in patients with schizophrenia at different stages of the illness and to explore its association with symptom severity and medication use. Methods: A total of 113 subjects were included, comprising 83 patients with schizophrenia divided into three groups: group A (acute drug-free symptomatic stage, n = 23), group B (chronic-medicated symptomatic stage, n = 30), and group C (chronic-medicated asymptomatic stage, n = 30). These were compared with a healthy control group (group D, n = 30). Participants were assessed using the Aberrant Salience Inventory (ASI) and clinical rating scales, including Psychotic Symptom Rating Scales, Scale for Assessment of Positive Symptoms, and Scale for Assessment of Negative Symptoms (SANS). Results: Significant differences were observed across almost all domains of aberrant salience. The most notable differences were between the symptomatic groups (A, B) and the healthy controls (D). Subgroup analysis showed no significant differences between the acute (A) and chronic groups (B, C), but significant differences were found between the symptomatic (A, B) and asymptomatic (C) groups in several domains and in the total ASI score. A highly significant positive correlation was noted between the total ASI score and the symptom rating scales, except for SANS. Conclusion: Aberrant salience is significantly elevated in patients with prominent positive symptoms, particularly delusions and hallucinations. It appears comparable to the general population in chronic remitted patients, suggesting that aberrant salience is state-dependent. Medication did not significantly influence aberrant salience as both medicated and nonmedicated symptomatic patients continued to exhibit it. However, medication may contribute to reducing aberrant salience by alleviating positive psychotic symptoms.

• We provide the first network meta-analysis comparing long-acting injectable antipsychotics and their oral counterparts for the acute treatment of schizophrenia. • The efficacy of long-acting injectable and oral antipsychotics for acute schizophrenia is similar. • Some side-effects may be less frequent under LAIs, although this pattern is not consistent across outcomes and drugs. Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase. [ABSTRACT FROM AUTHOR]

Mingjun Zhao,1,&ast; Bin Qin,2,&ast; Yage Mao,3 Hailing Wang,1 Aiqin Wang,1 Chuansheng Wang4 1Department of Pharmacy, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, Henan, People’s Republic of China; 2Department of Neurology, Liuzhou General Hospital, Liuzhou, Guangxi, People’s Republic of China; 3Department of Pharmacy, Maternal and Child Health Care Hospital of Xinxiang City, Xinxiang, Henan, People’s Republic of China; 4Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), Xinxiang, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuansheng Wang, Department of Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University (Henan Mental Hospital), 207# QianJin Road, Xinxiang, Henan, 453000, People’s Republic of China, Tel +86-373-3388772, Fax +86-373-3374082, Email chuansonwang@126.comPurpose: The 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 Methods: We 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.Results: Four 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).Conclusion: The 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.Keywords: brexpiprazole, placebo, acute schizophrenia, RCTs, meta-analysis

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. [ABSTRACT FROM AUTHOR]

Abstract Introduction Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random‐effect model network meta‐analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia. Methods The study included the double‐blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS‐T, primary), positive (PANSS‐P), negative (PANSS‐N), and general (PANSS‐G) subscale scores; and Clinical Global Impression‐Severity Scale (CGI‐S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events. Results We included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS‐T [standardized mean difference (95% credible interval): LUR40 = −0.298 (−0.420, −0.176), LUR80 = −0.170 (−0.320, −0.019)], PANSS‐P, and CGI‐S scores, LUR40 but not LUR80 outperformed placebo in PANSS‐N and PANSS‐G scores and response rate. LUR40 outperformed LUR80 regarding PANSS‐G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug‐Induced Extrapyramidal Symptoms Scale score. Conclusions Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms.

Introduction In spite of the long history of antipsychotic treatment there are still no clear criteria, which can be robust support for drug decision-making. Objectives To determine the important hallmarks of patient’s current state, life span and history of illness defining the doctor’s decision about the type of antipsychotic to be chosen. Methods The data from the case charts of 275 patients with episodic schizophrenia and rather benign course of the disease were analyzed. Results The group included: male 62%, mean age 33 (SD 11), education 10 years 23%, 13 years 27%, 16 years 29%, disability - 51%, number of hospitalizations due to psychotic episodes in the past 7 (SD 6). The symptoms of the current episode varied from patient to patient: delusions and hallucinations, symptoms of disorganization, negative symptoms of different severity were registered Atypical antipsychotics were more often than typical prescribed to the patients with developmental problems: traumatic obstetric complications (p=0,009), poor somatic health in the childhood (p= 0,02), cognitive dysfunction during school years (p=0,04), and quality of first remission – presence of residual symptoms in the first remission (p=0.005). Good compliance in the past was one more important factor for choosing a atypical antipsychotic for a patient (p=0.05). It appeared that the most important for the decision-making was the specific features of the patient’s development and early period of the disease, but not the specific signs of current psychotic state. Conclusions Doctor’s decision upon the type of antipsychotics in this category of patients is most probably based on other than current clinical symptoms signs.

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.

This study investigated factors associated with discontinuation in double-blind, randomized, placebo-controlled trials (DBRPCTs) of second-generation antipsychotics (SGAs) for acute schizophrenia, with a view to establishing what factors were associated with all-cause discontinuation. 77 eligible studies (96 comparisons; n = 22,678) were included in this study. Thirty-one factors potentially affecting all-cause discontinuation, related to the participants, study design, and drugs, were included in a meta-regression analysis that examined the factors associated with discontinuation rates in treatment and placebo groups and/or the treatment–placebo group difference in discontinuation. Smaller improvements in Positive and Negative Syndrome Scale total scores from baseline to endpoint were associated with higher discontinuation rates in both the treatment and placebo groups, and smaller response rates in the treatment group were associated with higher discontinuation rates in the treatment group. These factors were also associated with the treatment–placebo group difference in discontinuation. Although the risk of weight gain from SGA use was not associated with discontinuation rates in either the treatment or placebo groups, SGAs with a risk of weight gain were associated with a larger treatment–placebo group difference in discontinuation, although the reason is unknown. Factors associated with discontinuation rates in both treatment and placebo groups did not influence the treatment–placebo group difference in discontinuation. The efficacy and the risk of weight gain of SGAs seemed to influence treatment–placebo group difference in discontinuation in DBRPCTs of SGAs for acute schizophrenia. • This meta-regression analysis included 77 studies (n = 22,678). • The efficacy might influence in discontinuation. • The risk of weight gain of SGAs might influence in discontinuation. [ABSTRACT FROM AUTHOR]

Introduction: Considering that the efficacy results of the Japan lurasidone phase 3 trials for acute schizophrenia were inconsistent, we conducted a systematic review and a random‐effect model network meta‐analysis of those trials to examine whether lurasidone was beneficial for the treatment of Japanese patients with acute schizophrenia. Methods: The study included the double‐blind, randomized trial in Japan that included patients with acute schizophrenia. Efficacy outcomes were improvement of the Positive and Negative Syndrome Scale total score (PANSS‐T, primary), positive (PANSS‐P), negative (PANSS‐N), and general (PANSS‐G) subscale scores; and Clinical Global Impression‐Severity Scale (CGI‐S) score and response rate. Other outcomes were discontinuation rates and incidence of individual adverse events. Results: We included four studies (n = 1,608). Although both lurasidone 40 mg/d (LUR40) and 80 mg/d (LUR80) outperformed placebo in PANSS‐T [standardized mean difference (95% credible interval): LUR40 = −0.298 (−0.420, −0.176), LUR80 = −0.170 (−0.320, −0.019)], PANSS‐P, and CGI‐S scores, LUR40 but not LUR80 outperformed placebo in PANSS‐N and PANSS‐G scores and response rate. LUR40 outperformed LUR80 regarding PANSS‐G score. Both LUR40 and LUR80 were associated with a higher incidence of akathisia, somnolence, and increased body weight compared with placebo. Compared with placebo, LUR40 was associated with a higher incidence of weight gain (≥7%), and LUR80 was associated with a higher incidence of dystonia and weight loss (≥7%) and higher Drug‐Induced Extrapyramidal Symptoms Scale score. Conclusions: Both LUR40 and LUR80 improved overall symptoms in Japanese patients with acute schizophrenia. However, LUR80 seemed to have a risk of extrapyramidal symptoms. [ABSTRACT FROM AUTHOR]

Introduction The use of the blonanserin patch (BLO-P) for schizophrenia treatment was approved in Japan in 2019. This systematic review of trials in Japan assessed the efficacy and safety profile of BLO-P compared with other antipsychotics. Methods The systematic review included 6-week, double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with acute schizophrenia. Pooled data for patients receiving BLO-P 40 and 80 mg/day (BLO-P40+80) were compared with pooled data for patients receiving asenapine 10 and 20 mg/day (ASE10+20) and data for those receiving brexpiprazole 2 mg/day (BRE2) and paliperidone extended-release 6 mg/day (PAL-ER6). Results All the investigated treatments were superior to placebo in reducing the Positive and Negative Syndrome Scale (PANSS) total score; the Hedges' g values (95% confidence interval) for BLO-P40+80, ASE10+20, BRE2, and PAL-ER6 were−0.40 (−0.58,−0.22),−0.61 (−0.79,−0.42),−0.33 (−0.60,−0.07), and−0.69 (−0.93,−0.45), respectively. There were differences among the antipsychotics in the incidence of various individual adverse events. Discussion BLO-P40+80 may have a good efficacy/safety/tolerability profile for the treatment of patients with acute schizophrenia. [ABSTRACT FROM AUTHOR]

Rationale: What is the difference between aripiprazole and brexpiprazole? Objectives: This systematic review, network meta-analysis of randomized trials evaluated the efficacy and safety/tolerability of aripiprazole and brexpiprazole for treating acute schizophrenia. Methods: We searched Scopus, MEDLINE, and Cochrane Library from inception until May 22, 2019. The response rate was set as the primary outcome. Other outcomes were discontinuation rate and incidence of individual adverse events. The risk ratio (RR) and 95% credible interval (95%CrI) were calculated. Results: Fourteen studies were identified (n = 3925). Response rates of both aripiprazole and brexpiprazole were superior to that of the placebo (RR [95%CrI]: aripiprazole = 0.84 [0.78, 0.92], brexpiprazole = 0.84 [0.77, 0.92]). Aripiprazole and brexpiprazole were associated with a lower incidence of all-cause discontinuation (0.80 [0.71, 0.89], 0.83 [0.72, 0.95]), adverse events (0.67 [0.47, 0.97], 0.64 [0.46, 0.94]), and inefficacy (0.56 [0.40, 0.77], 0.68 [0.48, 0.99]) compared with the placebo. Although brexpiprazole was associated with a lower incidence of schizophrenia as an adverse event compared with the placebo (0.57 [0.37, 0.85]), aripiprazole and brexpiprazole were associated with a higher incidence of weight gain compared with the placebo (2.12 [1.28, 3.68], 2.14 [1.35, 3.42]). No significant differences were found in other individual adverse events, such as somnolence, akathisia, extrapyramidal symptoms, and dizziness between aripiprazole or brexpiprazole and placebo. Any outcome between aripiprazole and brexpiprazole were not different. Conclusions: Differences in short-term efficacy and safety for acute schizophrenia were not apparent between aripiprazole and brexpiprazole. Future studies are warranted to evaluate whether there are differences in the long-term outcome between treatments. [ABSTRACT FROM AUTHOR]

Objectives: Schizophrenia is the third leading cause of loss of life years in Thailand. Currently, aripiprazole is the latest drug for the treatment of acute schizophrenia in Thailand, but its cost-effectiveness has not been studied. The purpose of this study was to investigate the costeffectiveness of aripiprazole compared with risperidone. Methods: A Markov model was used to evaluate total costs and quality-adjusted life years (QALYs) over a lifetime horizon from a societal perspective. Clinical effectiveness was retrieved from previous studies. All cost data and mortality rates were retrieved from Thai data. Results: The results revealed that the total cost of the treatment with aripiprazole was 691,469.06 Baht compared to 692,200.88 Baht for risperidone, and the QALYs were 15.75 and 15.45 years, respectively. The acceptability curves demonstrated that the probability of aripiprazole being cost-effective was 97.5% of the willingness-to-pay, being 1.2 times the Thai gross national income per capita. Conclusions: Treatment of acute schizophrenia in Thailand with aripiprazole was showed greater QALYs and lower cost than treatment with risperidone. Treatment with aripiprazole is a dominant alternative. The results of this study could contribute to appropriate decision-making by policymaker. [ABSTRACT FROM AUTHOR]

Objective Numerous studies on the effects of seclusion and/or restraint in acute psychiatric treatment have reported both positive and negative effects. However, no studies to date have evaluated the effects of seclusion and/or restraint on schizophrenia patients using a rating scale. Thus, to examine the effects of seclusion and/or restraint on schizophrenia patients, we used the Brief Psychiatric Rating Scale and assessed the psychological condition of patients. Methods Factor analysis was conducted to create subscales of Brief Psychiatric Rating Scale, and psychiatric changes were assessed with respect to each subscale using multiple logistic regression analyses. Analyses were performed on three groups (i.e. entire, higher functioning, and lower functioning groups) involving a total of 1559 schizophrenia patients aged 18 to 65 years. Results In the entire and lower functioning groups, seclusion was a significant predictor of improvements related to the “hostility/suspiciousness” subscale. Seclusion combined with restraint was associated with improvements related to the “psychosis/thinking disorder” subscale. In the higher functioning group, there were no significant predictors. Conclusions It is implied that seclusion and/or restraint is related to improved psychiatric symptoms only among patients whose functioning is impaired. To verify the present findings, further studies involving multiple sites and additional psychiatric measures are necessary. [ABSTRACT FROM AUTHOR]

Background: Etiological research in schizophrenia is actively exploring biochemical toxic factor that may be result of an innate metabolic error - that factor is thought to be abnormal protein factor. Aim: The present study was undertaken to study the concentration of various protein fractions in acute schizophrenics, to find out the association of serum proteins in acute schizophrenia patients and to find out in what fraction of proteins an abnormality lies. Methods: Study consists of two groups, group one formed by healthy individuals, acting as controls and group two by acute schizophrenia patients. With all aseptic precautions, blood was collected and subjected to electrophoresis and for biuret reaction to find out fractional proteins and total proteins respectively. Analysis was done using Students "t" test. Results: In acute schizophrenics, decrease in albumin fraction was seen compared to control group, and increase in the ALPHA 1 and ALPHA 2 Fraction was seen in patients of acute schizophrenia as compared to healthy controls. Conclusion: Observation showed that there exists an abnormal protein fraction in acute schizophrenia patients. As seen in present research, there is decreased albumin level and increase in both Alpha -1 and Alpha-2 globulin fraction significantly as compared to controls. Alpha -2 fraction was more increased in patients with increased psychomotor activity. [ABSTRACT FROM AUTHOR]

Introduction: This single-group, open-label, prospective, noncomparative, multicenter, Phase IV study explored the efficacy and tolerability of paliperidone palmitate (PP) in hospitalized patients with acute exacerbation of schizophrenia. Methods: Asian patients of either sex, between 18 and 65 years of age, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) with acute exacerbations within the previous 4 weeks, were enrolled. Intramuscular PP was initiated at doses of 150 milligram equivalent (mg eq) (day 1) and 100 mg eq (day 8), followed by a monthly maintenance dose between 75 mg eq and 150 mg eq (days 36 and 64). Primary efficacy endpoint was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score (last-observation-carried-forward) at week 13. Results: Of the 212 enrolled patients, 152 (71.7%) completed the 13-week treatment; withdrawal of consent (24 [11.3%] patients) was the most common reason for study discontinuation. Mean (standard deviation) PANSS total score from baseline (90.0 [17.41]) improved significantly at day 4 (-6.1 [9.27]; 95% confidence interval: -7.38, -4.85; P<0.001) and week 13 endpoint (-23.9 [23.24]; 95% confidence interval: -27.10, -20.78; P<0.001). Similarly, the secondary endpoints (Clinical Global Impression-Severity, Physical and Social Performance, each PANSS subscale, and Marder factor scores) improved significantly from baseline to week 13 endpoint (P<0.001 for all). At week 13, 112/210 (53.3%) patients had a 40% improvement in the PANSS total score (responder rate), and 133/212 (62.7%) patients were ready for hospital discharge. Overall, 139 (65.6%) patients experienced at least one treatment-emergent adverse event (TEAE). Most common (>5%) TEAEs were hyperprolactinemia, constipation, nasopharyngitis, insomnia, increased weight, and tremor. Worsening of schizophrenia (3.3%) and sinus bradycardia (2.0%) were serious TEAEs; no deaths were reported. Conclusion: PP was generally tolerable and efficacious in a hospital setting for the treatment of acute exacerbated schizophrenia with significant improvements in psychotic symptoms, social functioning, and severity of illness. [ABSTRACT FROM AUTHOR]

Résumé Les auteurs présentent un cas de cannibalisme psychotique chez un homme célibataire de 26 ans, ancien militaire de carrière. Sous l’influence directe d’un trouble psychotique aigu avec délire mystique et sentiment de possession diabolique, ce patient paranoïde a tué un homme de 90 ans, puis dévoré une partie de sa langue et de son cœur. Il a par la suite agressé un autre homme et tenté sans succès de massacrer une famille. Placé en unité pour malades difficiles, ce psychotique anthropophage n’avait ni antécédent psychiatrique, ni condamnation antérieure. The authors present a case of psychotic cannibalism in a 26-year-old single man who was a former professional soldier. Under the direct influence of an acute psychotic disorder with mystical delusion and a feeling of demonic possession, this paranoid patient killed a man of 90 years and devoured part of his tongue and his heart. He later assaulted another man and tried unsuccessfully to kill a family. Placed in a unit for dangerous patients, this psychotic cannibal had no psychiatry history or previous conviction. [ABSTRACT FROM AUTHOR]

Abstract: The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed to explore treatment response, tolerability, and safety of flexible doses of paliperidone ER in patients with schizophrenia admitted for an acute exacerbation. This paper addresses a secondary analysis of PERTAIN data designed to explore predictors for treatment response, flexible dosing, and concomitant benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single-arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily) to treat patients hospitalized for an acute exacerbation of schizophrenia, reflecting more closely daily clinical practice. Predictive models were evaluated for paliperidone ER flexible dosing, treatment response, and concomitant treatment with benzodiazepines as distinct independent variables. For the analysis of explanatory variables, a stepwise logistic regression was used, taking into account patient age, gender, body mass index, diagnosis and duration of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS), disease severity (CGI-S), and patient functioning (PSP) at baseline. Early response (defined as response within 2weeks of treatment initiation) was also used as a predictor. Clinical response (defined as ≥30% decrease in PANSS total score and ≥1 point decrease in CGI-S from baseline to endpoint) was predicted by early clinical response (p <0.001) and there was a trend for the diagnosis of paranoid schizophrenia vs. other types of schizophrenia to predict clinical response (p =0.0525). High response (defined as ≥50% decrease in PANSS total score and ≥2 points decrease in CGI-S from baseline to endpoint) was predicted by early high response, higher baseline CGI-S, or female gender. More severely ill patients with a higher baseline CGI-S were twice likely to be treated concomitantly with a benzodiazepine. [Copyright &y& Elsevier]

Objective: First-month data of a 13-week acute schizophrenia study were used to compare paliperidone palmitate to oral risperidone during initiation of long-acting injectable risperidone. Design: Double-blind, randomized study. Setting: Outpatient or inpatient. Participants: Adults with established (³1 year) schizophrenia. Those assigned to risperidone longacting injectable (n=460) received 25mg on Days 8 and 22 with oral risperidone (1-6mg) supplementation for the first 28 days. The paliperidone palmitate group (n=453) received 150mg eq. on Day 1, 100mg eq. on Day 8, and oral placebo supplementation for the first 28 days. Measurements: Positive andNegative Syndrome Scale, Personal and Social Performance Scale, Clinical Global Impression-Severity score, and responder rate (percentage of patients with ³30% reduction in PANSS total score). An analysis of covariance model. [ABSTRACT FROM AUTHOR]

Abstract: Background: Effective emergency intervention for acute schizophrenia is of great concern to psychiatrists. To investigate whether differences in attitudes toward pharmacotherapy exist in the emergency setting, we surveyed two regions of Japan. Methods: The subjects were 100 psychiatrists. The clinical experience of all subjects was not more than 15 years. A questionnaire with a case vignette was sent to them and returned anonymously. Thirty-five out of 42 subjects in Hokkaido and 30 out of 58 subjects in Fukuoka responded. Results: We found a difference in the preferred route of administration of haloperidol, the agent chosen by 46.2% of the respondents. Most psychiatrists in Hokkaido preferred intravenous administration, but none of the Fukuoka psychiatrists chose this route preferring intramuscular administration. The mean dose of haloperidol was significantly higher in Hokkaido (7.29±2.5mg) compared to that in Fukuoka (5.56±1.7mg). Conclusion: The difference in preferred route of administration and dose of haloperidol probably reflects the content of training at each hospital and suggests that early training determines the subsequent clinical custom of each psychiatrist. [Copyright &y& Elsevier]

Even though the relief of symptoms can be achieved with the treatments used in schizophrenia, the re-gain of the functioning cannot be established to that extent. Patients can have difficulties in the social adaptation, impairment in interpersonal relations, problems in family communication, difficulties in occupational functioning, and inadequacy in self-care. Personal and Social Performance Scale (PSP) is a comprehensive and sensitive to change instrument developed for the assessment of social functioning in schizophrenia. Paliperidone provides significant remission in social functioning assessed with PSP. The pooled data of the three clinical trials with paliperidone are re-analyzed. In the analyses, paliperidone 3 mg provided an improvement of 8.3±17.1 in the PSP score, for 6 mg it is 9.0±14.8, for 9 mg 7.8±14.3, for 12 mg 9.5±15.0, and for 15 mg it is 12.2±15.7. With placebo, the reduction in the PSP score is 0.5±15.0. When the improvement of at least one category (i.e. one ten-point interval) is taken into consideration, 50.4% of the patients in the treatment of 3 mg of paliperidone, 56.1% in the 6 mg group, 49.6% in the 9 mg group, 54.1% in the 12 mg group and 63.6% in the 15 mg group achieved improvement. Patients in the paliperidone group improved significantly in social functioning when compared with patients in the placebo group. In acute schizophrenia with six-week treatment, paliperidone appears to be effective in the improvement of impairment in social functions. [ABSTRACT FROM AUTHOR]

Little has been published regarding the pharmacokinetics of the intramuscular (IM) formulation of Ziprasidone. The authors report results from 2 early phase I studies in healthy volunteers: a trial of single 5-, 10-, or 20-mg IM doses of ziprasidone in 24 subjects and an open-label 3-way crossover trial of 5-mg intravenous (IV), 5-mg IM, and 20-mg oral ziprasidone in 12 subjects. Absorption of IM ziprasidone was rapid (Tmax < 1 hour). The IM pharmacokinetic profile was consistent between studies and linear, with dose-related increases in exposure observed. The mean IM elimination t1/2was short and approximately 2.5 hours. The mean bioavailability for the 5-mg IM ziprasidone dose was approximately 100%. Adverse events were generally mild to moderate, and no subjects were discontinued from the study. No significant effects on renal function or other laboratory values were noted. These results support the use of IM ziprasidone in treating acutely agitated patients with schizophrenia. [ABSTRACT FROM PUBLISHER]

Abstract: Learned irrelevance (LIrr) is a pre-exposure effect in which uncorrelated presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US) retard subsequent CS-US association. LIrr is closely related to the phenomenon of latent inhibition (LI). LI refers to the retarding effects of inconsequential stimulus pre-exposure on subsequent conditioning to that stimulus, and is considered to reflect the organism''s capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the preexposed CS and the US. A new within-subject target-recognition LIrr procedure was applied. The target was either cued by a priming signal or appeared at random, and priming signals were novel or preexposed cues. Schizophrenia patients were compared to age- and sex-matched control subjects. Normal subjects (n =24) have shown robust LIrr, namely, faster cue-target associations of novel compared to preexposed cues. Schizophrenia patients at the early stages of their first episode (n =7) showed LIrr disruption, namely, cue-target associations to preexposed cues were as fast as for novel cues. Chronic patients during an acute phase (n =18) did not show LIrr as they failed to learn the cue-target association. In addition to the LIrr paradigm the same subjects were tested in a covert-orientation task. No differences were observed between the groups on this task. The possible advantages of the new LIrr paradigm are discussed. [Copyright &y& Elsevier]

Rationale: Conventional intramuscular (IM) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia. Objectives: To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizo-affective disorder. Methods: In a 6-week, multicenter, parallel-group, flexibly dosed study, patients were randomized to ziprasidone (IM up to 3 days, then oral 40-80 mg, b.i.d.) or haloperidol (IM up to 3 days, then oral 5-20 mg/day). Assessments were rater-blinded. Results: At the end of IM treatment, patients receiving ziprasidone (n=427) showed significantly improved Brief Psychiatric Rating Scale Total (BPRS total) scores compared with those receiving haloperidol (n=138) [least-squares (LS) mean change -6.14 for ziprasidone versus -4.13 for haloperidol, P<0.0018]. At endpoint, there were no significant between-group differences in BPRS total scores. There was a significantly greater improvement in BPRS negative subscale scores in ziprasidone-treated patients, both at the end of IM treatment (LS mean change -1.15 for ziprasidone and -0.28 for haloperidol, P<0.0001) and at study endpoint (LS mean change -2.94 for ziprasidone and -2.24 for haloperidol, P<0.0001). Haloperidol-treated patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment and at endpoint (P<0.0001). They also had significantly higher ratings on the Barnes Akathisia Scale (P<0.0001) and the Movement Disorder Burden Score (P<0.005), as well as higher incidences of movement disorder-related adverse events. Conclusions: Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia. [ABSTRACT FROM AUTHOR]

Abstract: Learned irrelevance (LIrr) is closely related to latent inhibition (LI). In LI a to-be-conditioned stimulus (CS) is prexposed alone prior to the opportunity to learn an association between the CS and an unconditioned stimulus (UCS). In LIrr preexposure consists of intermixed presentations of both CS and UCS in a random relationship to each other. In both paradigms preexposure leads in normal subjects to reduced or retarded learning of the CS–UCS association. Acute schizophrenics fail to show LI. LI is usually demonstrated as a one-off, between-groups difference in trials to learning, so posing problems for neuroimaging. We have developed a novel, continuous, within-subject paradigm in which normal subjects show robust and repeated LIrr. We show that this paradigm is suitable for functional magnetic resonance imaging (fMRI) and gives rise, in normal subjects, to activation in the hippocampal formation, consistent with data from animal experiments on LI. We also report, consistent with previous studies of LI, loss (indeed, significant reversal) of LIrr in acute (first 2 weeks of current psychotic episode) schizophrenics. Chronic schizophrenics failed to demonstrate learning, precluding measurement in this group of LIrr. These findings establish the likely value of the new paradigm for neuroimaging studies of attentional dysfunction in acute schizophrenia. [Copyright &y& Elsevier]

Abstract: Purpose. – This open label study was performed to evaluate the relationship between the plasma concentration of olanzapine and the response in acute schizophrenic inpatients. Material and methods. – A total of 54 inpatients, 38 males and 16 females, age ranging from 18 to 75 years, affected by Schizophrenia (DSM IV criteria) during an exacerbation phase were included in the study. Olanzapine (OLZ) was started at a dose of 5–20 mg/day and was increased to a mean dose of 15.27 mg ±5.53 S.D. Patients were evaluated at baseline, and after 2 weeks, by using BPRS, PANNS, HRS-D, EPSE, and ACS. Results. – BPRS and total PANSS showed a statistically significant improvement at the end of the study. Olanzapine plasma levels (PL) ranged from 5 to 120 ng/ml (mean 33.15 ng/ml ± 28.28 S.D.) and showed a positive correlation with OLZ dosage. A significant curvilinear correlation between OLZ PL and clinical improvement (BPRS, PANSS and HRS-D percent of amelioration) was observed. Conclusion. – Olanzapine plasma level determination seems to be a useful tool in optimizing acute treatment particularly for more problematic cases. [Copyright &y& Elsevier]

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