Positive And Negative Syndrome Scale Excited Component Research Articles

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder

BackgroundHostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. MethodsData were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3–12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS–Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. ResultsMost patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [−0.93], disruptive-aggressive behavior [−0.79], combined [−1.75]; P ≤ 0.001 each), YMRS total score (−5.92, P ≤ 0.0001), and all individual YMRS items (−0.25 to −0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LimitationsPost hoc analysis. ConclusionCariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

Efficacy of Atypical-Atypical and Atypical-Typical Antipsychotic in Indonesia Psychotic Mental Disorder Patients

It is approximately 7% of Indonesian people undergo psychotic mental disorder or schizophrenia. Special Region of Yogyakarta in Indonesian is on the second rank as the area whose high number of schizophrenia; for about 10 occurrences per 1000 citizens and 80% of patients treated at psychiatric hospital are caused by schizophrenia. A response of a medication therapy can be measured through doctor diagnosis based on the measurement parameter such as The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and Global Assessment of Functioning (GAF). Those two parameters are important variables that will be shown objectively by the assessment results. This research aimed to find out the different value of PANSS-EC and GAF, before and after the therapy of atypical-typical and atypical-typical on the schizophrenia patients at Psychiatric Hospital of Grhasia Yogyakarta. The research design here is Prospective Cohort. The criteria of inclusive patient was adults (18-65 years old), being hospitalized, undergoing atypical-atypical and atypical-typical therapy, and possessing complete medical record. The research data were gained from the medical records which then analyzed using univariate test to illustrate the patient distribution. Bivariate test was conducted to compare and correlate the value of PANSS-EC and GAF. The number of samples were 32 patients which were divided into 2 groups; atypical-atypical (n=16) and atypical-typical (n=16). The results showed that the value of PANSS-EC after therapy in both groups experienced a significant decrease (p=0.001). However, there was no significant difference between the two groups of patients with psychotic mental disorders or schizophrenia in a mental hospital and there reseach no significant difference in effectiveness between doses and frecuency of antipsychotic therapy regimens in schizophrenic patients with a significant value of p>0.05

The safety and efficacy of sequential intramuscular/oral ziprasidone treatment of acute episode in patients with schizophrenia: a multicenter, open-labeled study

BackgroundZiprasidone 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.MethodsA 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.ResultsOut 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.ConclusionsZiprasidone 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 registrationThe Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn: ChiCTR-OIC-16007970.

Positive and Negative Syndrome Scale (PANSS) predictors of hospitalization during home treatment on 1045 patients with schizophrenia in acute crisis

IntroductionSeveral factors related to the risk of requiring psychiatric hospitalization have been described in patients diagnosed with schizophrenia treated with methods other than home treatment. With regard to the symptoms, high global illness severity and positive symptoms of schizophrenia have been most frequently related to the risk of hospitalization in patients with schizophrenia. However, there are no studies describing which clinical factors increase the likelihood of being hospitalized while undergoing home follow-up.ObjectivesTo determine which of the clinical factors assessed in the PANSS predict the risk of hospitalization in patients diagnosed with schizophrenia following a home treatment program.MethodsAll patients with schizophrenia who were visited by a home treatment team in Barcelona between January 2017 and December 2021 were included in the study. A comparative, bivariate analysis of each item of the PANSS and of the global results of each category was conducted on those who were hospitalized and those who were not hospitalized. Finally, a logistic regression of each category of the PANSS was done on both groups, controlling for other socio-demographic and clinical factors.ResultsA total of 1045 patients with schizophrenia were evaluated in this study. PANSS positive symptom subscale (PANSS-S), PANSS General Psychopathology, PANSS Excited Component and PANSS Global Score scored higher in patients who were finally hospitalized in a conventional acute treatment unit. Regarding the PANSS negative symptom subscale, no significant differences were found between the two groups.In patients who required hospitalization, the scores of all the PANSS positive symptom subscale (PANSS-P) items and all items on the PANSS excited component (excitement, tension, hostility, uncooperativeness and poor impulse control) were significantly higher. Some items regarding general psychopathology (Somatic concern, anxiety, guilt feelings, tension, and mannerisms) were also significantly higher in the hospitalization group. Only 3 items—blunted affect, guilt feelings and motor retardation—scored significantly higher in patients who did not require hospitalization. In the logistic regression, only the global score of the PANSS-P reached statistical significance (P = 0.001).ConclusionsPositive symptoms scored in the PANSS seem to be the most predictive factors of hospitalization regarding clinical symptoms in patients with Schizophrenia following home treatment. Other items regarding exciting symptoms and general psychopathology also showed as relevant regarding the risk of conventional hospitalization in those patients.Disclosure of InterestNone Declared

EVALUATION OF CLINICAL OUTCOME OF ANTIPSYCHOTIC THERAPY IN SCHIZOPHRENIC PATIENTS IN PALU – INDONESIA

Schizophrenia is a severe mental disorder characterized by psychotic episodes. The first line of treatment for schizophrenia is the use of antipsychotics that is still subjective. There is still a need for research related to the use of antipsychotics to achieve effective treatment. This study aimed to compare the effectiveness of the First-Generation Antipsychotic (FGA) haloperidol, trifluoperazine and risperidone antipsychotic therapies as Second-Generation Antipsychotic (SGA) based on symptom reduction using the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) method in patients with acute schizophrenia and relapse hospitalization. This research used a quantitative analysis with a prospective approach where the sampling was conducted using total sampling and the data obtained were analyzed using independent t-test and linear regression analysis. There were 40 out of 120 patients who met the inclusion criteria, consisting of patients in groups of haloperidol, trifluoperazine and risperidone therapies with a therapeutic duration of 3–10 days. The results showed that the average PANSS-EC score of haloperidol medication of 15.35 was greater than that of trifluoperazine medication of 14.42 and the p-value showed no significant difference between the use of FGA, haloperidol and trifluoperazine with p = 0.190 (p&gt; 0.05). The average PANSS-EC score of haloperidol medication (FGA) of 15.35 was greater than that of risperidone (SGA) of 13.6 and the p-value showed that there was a significant difference between haloperidol and risperidone with p = 0.027 (p&lt; 0.05). The multivariate analysis showed p = 0.022 (p&lt; 0.05) which means haloperidol showed the greatest symptom reduction among the three antipsychotic medications.

72 Orally Dissolving, Thin Film Dexmedetomidine (BXCL501) Demonstrates Significant Reduction in Agitation Across a Range of Agitation Severity in Patients With Schizophrenia and Bipolar Disorder

Patients with bipolar disorder and schizophrenia experience acute agitation episodes that may require urgent management to avoid escalation. BXCL501 is an investigational orally dissolving thin film of the highly selective alpha-2a adrenergic receptor agonist, dexmedetomidine, for sublingual or buccal administration. This secondary analysis of 2 Phase 3 studies of acute agitation in patients with schizophrenia or bipolar disorder evaluated efficacy by baseline agitation severity on both the PANSS-Excited Component (PEC) total and the 5 items making up the PEC (excitement, tension, hostility, uncooperativeness, poor impulse control). Data were from 2 Phase 3, randomized, placebo-controlled studies of adults with bipolar disorder or schizophrenia, with a total score of ³14 on the PEC and ³4 on at least 1 of the 5 PEC items. Patients were randomized to either BXCL501 180 mg, 120 mg, or placebo. The primary endpoint was change from baseline PEC total score at 2 hours. Moderate and severe agitation were defined as a PEC total score of 14 to 19 or >19, respectively. Calmness was rated on the Agitation and Calmness Evaluation Scale (ACES). Mean change in PEC total score from baseline to 2 hours postdose was significantly (P < .0001) greater for 180 mg (-10.4 & -10.4) and 120 mg (-8.4 & -9.0) doses of BXCL501 vs placebo (-4.7 & -4.9) for the schizophrenia & bipolar groups, respectively. Significant (P < .01) improvements from baseline to 2 hours in PEC total score were observed with BXCL501 vs placebo among subgroups with moderate or severe agitation. Significant (P < .0001) improvements from baseline in each of the 5 components of the PEC were observed with both doses of BXCL501 compared to placebo. These findings were consistent in both the schizophrenia and bipolar disorder groups. There were no severe or serious drug-related adverse events. Safety and tolerability results were comparable in both trials. In the schizophrenia study, the most common treatment emergent adverse events (TEAEs) were somnolence (22%; 86% mild, 14% moderate), dizziness (4.3%), oral hypoesthesia (4.3%), and orthostatic hypotension (4.0%) In the bipolar disorder study, the most common TEAEs were somnolence (21%; 59% mild, 41% moderate), dry mouth (5.6%), dizziness (5.6%), hypotension (5.6%), and orthostatic hypotension (4.4%). No participant was unarousable as measured by the ACES. All participants were able to self-administer the film. BXCL501, an investigational orally dissolving thin film formulation of dexmedetomidine, demonstrated consistent statistically significant improvement in PEC total score compared to placebo, regardless of baseline agitation severity in both schizophrenia and bipolar disorder groups. Statistically significant improvement in PEC total and all individual items (excitement, tension, hostility, uncooperativeness, poor impulse control) was observed with both doses in both groups. The most common TEAEs in both groups were somnolence, dizziness, and orthostatic hypotension. BXCL501 represents a potential approach for treating acute agitation in adults with schizophrenia and bipolar disorder.

M47. AKATHISIA AND ATYPICAL ANTIPSYCHOTICS: EXPLORING ASSOCIATIONS TO SUICIDALITY AND AGITATION

BackgroundAntipsychotic associated akathisia is a highly relevant clinical phenomenon. The common side effect can be stigmatizing, cause subjective distress and depression, lead to medication noncompliance and be potentially disabling for patients with psychosis. Associations between akathisia and both suicide, depression and agitation has been suggested in research literature, but inconsistently. This study investigates the level of akathisia at hospital discharge/first follow-up for consecutively admitted patients with acute phase psychosis, comparing four atypical antipsychotics (AAPs) regarding the presence of akathisia, and explores possible associations between akathisia and both suicidality, depression and agitation.MethodsThis study is a sub-study of the Bergen Psychosis Project (BPP), a pragmatic, rater-blind, randomized trial comparing head-to-head ziprasidone, olanzapine, risperidone and quetiapine. The present study reports cross-sectional data at discharge/first follow-up after acute admission to hospital for patients with psychosis. Patients were assessed with The Positive And Negative Syndrome Scale (PANSS). We applied the validated PANSS Excited Component (PANSS-EC) factor to assess agitation. The PANSS-EC consists of the five PANSS items: P4 Excitement, P7 Hostility, G4 Tension, G8 Uncooperativeness and G14 Poor impulse control. To assess depression in general and suicidality specifically we used the validated Calgary Depression Scale for Schizophrenia (CDSS).Furthermore the Clinical Global Impression – Severity Scale (CGI-S), and the patient-administered version of the UKU Side Effect Self-Rating Scale (UKU SERS Pat).ResultsA total of 109 patients were included of which 35 (32.1 %) were females, mean age was 34.0 (12.4). The mean total PANSS score was 54.9 (14.4), the mean CGI-S was 3.7 (1.1) and the mean total CDSS score was 3.9 (4.0). Our preliminary results show that a total of 58 (53.3%) patients had used antipsychotics before entering the study. Some level of akathisia was reported by ¼ of the patients, meaning a score of 1 or more on the UKU SERS Pat. There was a statistically significant difference between ziprasidone and olanzapine, with higher akathisia level in the ziprasidone group. Furthermore, there were statistically significant correlations between akathisia and suicidality and between akathisia and depression. We found no significant correlation between akathisia and the PANSS-EC factor or between akathisia and the PANSS general item G14 Poor impulse control. Statistical details will be presented on the poster.DiscussionOur study shows that akathisia is a prevalent side effect in a clinically relevant sample of patients with acute phase psychosis treated with atypical antipsychotics. The prevalence of antipsychotic associated akathisia ranges widely across studies due to, among others, methodological heterogeneities and varieties in measurement tools. In our study, akathisia was significantly associated with both depression and suicidality. The finding of a significant correlation between akathisia and suicidality supports a previous finding that even a mild to moderate experience of akathisia in first episode patients had an increase in the likelihood to be suicidal. We found no relationship with agitation in our study. As akathisia may go unrecognized in clinical practice and may contribute to medication noncompliance, systematic assessment for symptoms of akathisia is warranted.ConclusionAkathisia is still a prevalent phenomenon in a substantial proportion of patients treated with atypical antipsychotics. Special attention is called for regarding the association towards suicidality.

Clinical study on diazepam combined with olanzapine in treatment of agitation in alcohol withdrawal delirium tremors

Objective To compare the efficacy and safety of diazepam combined with olanzapine in treatment of agitation symptoms in patients with alcohol withdrawal delirium tremors(DT). Methods Totally 60 inpatients with DT according to CCMD-3 were enrolled in a 7-day, with 30 patients in the diazepam group (control group) and 30 patients in diazepam combined with olanzapine group (research group). The delirium rating scale(DRS-R-98) was used to evaluate the severity of the delirium symptoms. The positive and negative syndrome scale excited component(PANSS-EC) was used to assess the agitation symptoms.The treatment emergent symptom scale (TESS) was used to assess the safety and the vital signs. Results There was no significant difference in the delirium recovery time between the two groups(M(QR): 24 h(24 h)vs 24 h(6 h))(Z=-0.45, P=0.65). The PANSS-EC score in research group(17.00±2.67) was significant lower than that in control group(19.80±2.43) at the 6 hours after treatment(t=4.26, P 0.05). One case of dizziness, 2 cases of lethargy in the control group; 1 case of nasal congestion, 5 cases of drowsiness, 3 cases of constipation, 3 cases of dry mouth, 1 case of abnormal liver function in the research group. Conclusion The combination of olanzapine with diazepam can not reduce the recovery time of DT, but can quickly improve the agitation behavior. Key words: Delirium tremors; Agitation behavior; Diazepam; Olanzapine

Psychomotor agitation in subjects hospitalized for an acute exacerbation of Schizophrenia

The aims of this study were to establish the prevalence of moderate and severe psychomotor agitation in patients hospitalized for an active phase of schizophrenia, the associations between psychomotor agitation and patients’ demographic and clinical variables, the intra-individual stability of the agitated/non-agitated dichotomy in independent psychotic breakdowns. The study was performed on a database relative to 630 inpatients hospitalized with a diagnosis of schizophrenia. Psychomotor agitation was measured with the Positive and Negative Syndrome Scale – Excited Component (PANSS-EC). Prevalence of moderate and severe psychomotor agitation was 40.5% and 23.7%, respectively. Non-agitated patients were older, with longer illness history and duration of untreated psychosis, were more frequently on antipsychotic medication, had lower incidence of recent use of substances, and functioned better before the index hospitalization than moderately and/or severely agitated patients. Non-agitated patients had lower scores for total PANSS and Emsley's positive and anxiety dimensions. Compared with the severely agitated group, non-agitated and moderately agitated patients scored more in Emsley's depression dimension. Poor functioning before index hospital admission, higher scores for negative subscale and Emsley's positive dimension and use of substances exerted an effect on risk of psychomotor agitation.

Safety and effectiveness of rapid-acting intra-muscular olanzapine for agitation associated with schizophrenia - Japan postmarketing surveillance study.

ObjectiveThe objective of this study was to evaluate the safety and effectiveness of rapid-acting intramuscular (IM) olanzapine in the treatment of acute agitation associated with schizophrenia in real-world clinical settings in Japan.MethodsIn this multicenter, postmarketing surveillance (PMS) study, patients with acute agitation associated with schizophrenia were treated with IM olanzapine daily in a daily clinical setting. The observational period ranged from 1 to 7 days, including the day of initial administration. Safety was assessed by reporting treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs). The Positive and Negative Syndrome Scale – Excited Component (PANSS-EC) score was used to evaluate effectiveness at baseline and at 2 hours (after each administration), 2 days, and 3 days (end of the observational period) from the last administration of the IM olanzapine injection.ResultsThe safety analysis set included 999 patients, and the initial dose of 10 mg was administered to 955 patients. TEAEs were reported in 28 patients (36 events), the most common of which were dyslalia (5 patients), akathisia and somno lence (4 patients each), hepatic function abnormal (3 patients), and constipation and dehydration (2 patients each). One serious adverse event of akathisia occurred during the observation period. The PANSS-EC score (mean ± standard deviation) was 23.3±6.4 (n=625) at baseline, 16.9±7.0 (n=522) at 2 hours after initial injection, and 14.9±6.5 (n=650) at the last observation carried forward.ConclusionThe results of this Japanese PMS study demonstrated that IM olanzapine is safe and has a favorable effectiveness profile in the treatment of schizophrenia patients with acute agitation.

Effects of asenapine on agitation and hostility in adults with acute manic or mixed episodes associated with bipolar I disorder.

BackgroundBipolar disorder is associated with an increased risk of aggression. However, effective management of hostility and/or agitation symptoms may prevent patients from becoming violent. This analysis investigated the efficacy of the antipsychotic asenapine on hostility and agitation in patients with bipolar I disorder.MethodsData were pooled from three randomized, double-blind, placebo-controlled, Phase III trials of asenapine in adults with manic or mixed episodes of bipolar I disorder (NCT00159744, NCT00159796, and NCT00764478). Post hoc analyses assessed the changes from baseline to day 21 on the Young Mania Rating Scale (YMRS) and the Positive and Negative Syndrome Scale (PANSS) hostility-related item scores in asenapine- or placebo-treated patients with at least minimal or mild symptom severity and on the PANSS-excited component (PANSS-EC) total score in agitated patients. Changes were adjusted for improvements in overall mania symptoms to investigate direct effects on hostility.ResultsSignificantly greater changes in favor of asenapine versus placebo were observed in YMRS hostility-related item scores (irritability: least squares mean difference [95% confidence interval] =−0.5 [−0.87, −0.22], P=0.001; disruptive–aggressive behavior: −0.7 [−0.99, −0.37], P<0.0001), PANSS hostility item score (−0.2 [−0.44, −0.04]; P=0.0181), and PANSS-EC total score (−1.4 [−2.4, −0.4]; P=0.0055). Changes in the YMRS disruptive–aggressive behavior score and the sum of the hostility-related items remained significant after adjusting for improvements in other YMRS item scores.ConclusionAsenapine significantly reduced hostility and agitation in patients with bipolar I disorder; improvement was at least partially independent of overall improvement on mania symptoms.

Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses.

BackgroundEfficacy of inhaled loxapine 5 or 10 mg in treating agitation was shown using the Positive and Negative Syndrome Scale – Excited Component (PANSS-EC) in two Phase III randomised, double-blind, placebo-controlled trials in 344 agitated patients with schizophrenia and 314 patients with bipolar I disorder (Clinicaltrials.gov: NCT00628589, NCT00721955).AimsTo examine the five individual items comprising the PANSS-EC and the percentage of patients achieving a clinical response (reduction of ≥40%) in PANSS-EC (Response-40) for these two studies.MethodResponse-40 was examined at the primary end-point (2 h) and over time.ResultsResponse-40 and each PANSS-EC item score were statistically significant v. placebo at 2 h and at each assessment time point for both doses.ConclusionsInhaled loxapine produced rapid improvement in agitated patients with schizophrenia or bipolar I disorder, achieving Response-40 at the first assessment (10 min post dose). These results highlight the effectiveness of loxapine across all components of agitation as measured by the PANSS-EC.Declaration of interestS.Z. is a member of the speakers bureau for Grupo Ferrer. L.Z. has been a speaker and grant recipient for Teva Pharmaceuticals. J.V.C. and D.A.S. were employees of Alexza Pharmaceuticals during execution of the studies, and are currently paid consultants for and have received stock and/or stock options from Alexza Pharmaceuticals. P.P.Y. is a full-time employee and receives stock options from Teva Pharmaceuticals.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Efficacy of lurasidone in the treatment of agitation: A post hoc analysis of five short-term studies in acutely ill patients with schizophrenia.

This post hoc analysis evaluated the effect of lurasidone on agitation in acutely ill patients with schizophrenia. Patient-level data were pooled from five 6-week, randomized, double-blind, placebo-controlled studies of fixed-dose, once-daily, oral lurasidone (40, 80, 120, or 160 mg/d). Agitation was assessed with the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) score, utilizing a mixed model for repeated measurement analysis. In patients with higher levels of agitation at baseline (PANSS-EC score≥14; n=773), lurasidone was associated with significantly greater improvement in least-squares (LS) mean PANSS-EC scores versus placebo at Day 3/4 (-1.6 vs -1.0; p<0.05), Day 7 (-2.3 vs -1.6; p<0.05), and at Week 6 endpoint (-5.5 vs -3.8; p<0.001; effect size=0.43). In patients with lower agitation at baseline (PANSS-EC score<14; n=754), LS mean PANSS-EC score change was significantly greater for lurasidone compared with placebo at Day 7 (-0.8 vs -0.1; p<0. 01) through Week 6 endpoint (-1.9 vs -0.9; p<0.001; effect size=0.31). Higher doses of lurasidone were notably more effective than lower doses in patients with more severe agitation at study baseline. In this pooled analysis of 5 short-term studies, lurasidone provided early and sustained reduction in agitation, assessed using the PANSS-EC score, in patients with an acute exacerbation of schizophrenia. Higher doses of lurasidone were particularly effective in patients with more severe agitation at study baseline. Overall, these results suggest that lurasidone may be a useful treatment option for patients exhibiting agitation associated with acute psychotic symptoms of schizophrenia. ClinicalTrials.gov Identifiers: NCT00088634 (Study D1050196); NCT00549718 (Study D1050229), NCT00615433 (Study D1050231); NCT00790192 (Study D1050233). Study D1050006 was completed prior to the requirement to register trials.

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia: Post Hoc Analysis of Positive and Negative Syndrome Scale Marder Factor Scores.

BackgroundLong-acting injectable antipsychotics are treatment options for acute and long-term treatment of patients with schizophrenia. In a previously published 12-week randomized, double-blind, placebo-controlled clinical trial of patients with schizophrenia experiencing an acute psychotic episode, aripiprazole once-monthly 400 mg (AOM 400) produced significantly greater improvement than placebo on the primary endpoint, Positive and Negative Syndrome Scale (PANSS) total score at week 10.MethodsTo examine the efficacy of AOM 400 across a broader representation of schizophrenia symptoms, including agitation, a post hoc analysis of this trial was carried out to assess the change in PANSS Marder factor domains (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression) and the PANSS excited component (equivalent to Marder factor domain uncontrolled hostility/excitement plus the tension item) by comparing differences in change from baseline between AOM 400 and placebo using a mixed model for repeated measures.ResultsThe differences between treatment and placebo for all factors were statistically significant, with improvements seen as early as week 1 or 2, and maintained through week 12. Thus, AOM 400, supplemented with oral aripiprazole in the first 2 weeks, showed significantly greater efficacy versus placebo in acutely ill patients with schizophrenia in all 5 Marder illness domains, as well as in agitation as conceptualized by the PANSS excited component score.ConclusionsThese findings indicate that AOM 400 is efficacious across the spectrum of schizophrenia symptoms in acutely ill patients, with implications for both short-term and, by extension, long-term patient outcomes.

Plasma levels of Th17-related cytokines and complement C3 correlated with aggressive behavior in patients with schizophrenia.

Increasing evidence indicates that immune inflammatory processes, especially autoimmune reaction, should be considered in the pathophysiology of schizophrenia and aggressive behavior. The present study aimed to explore the correlation between immune factors (C3 and Th17-related cytokines) and aggressive behavior in schizophrenia patients. Forty schizophrenia patients and forty age- and gender-matched healthy controls participated in the study. Blood samples were assessed by ELISA upon enrollment. Positive and negative syndrome scale (PANSS) and modified overt aggression scale (MOAS) were used to estimate the severity and aggressive symptoms of schizophrenia patients. Plasma levels of IL-17, IL-23, and TGF-β1 in schizophrenia patients were significantly higher than those in healthy controls [(37.63±17.82) vs. (29.34±10.38)pg/ml, p=0.02; (101.40±135.26) vs. (13.09±5.94) pg/ml, p=0.01; (2864.57±2163.61) vs. (1839.69±1797.73)pg/ml, p=0.04], whereas C3 levels were significantly lower in schizophrenia patients [( 120,479.67± 65,612.50) vs. ( 208,060.21± 217,008.21)ng/ml, p=0.02]. IL-17, IL-23, and TGF-β1 levels were positively related to total scores of MOAS (p=0.02, p=0.02 and p=0.03, respectively) and PANSS (p=0.04, p=0.04 and p=0.02, respectively), whereas C3 levels were negatively related to total PANSS scores (p=0.03). IL-17 and IL-23 levels were positively correlated with PANSS excited component scores (p=0.04 and p=0.01, respectively). Our findings suggested that the Th17-related cytokine levels were positively related to the severity of schizophrenia and aggressive behavior, whereas C3 levels were negatively related to the severity of schizophrenia. This study demonstrated that elevated levels of Th17-related cytokines and decreased levels of C3 could be potential biomarkers for schizophrenia and aggressive behavior.

Use of inhaled loxapine in acute psychiatric agitation

ObjectivesThe aim of this work is to study the efficacy of loxapine inhalation powder on agitated patients in a psychiatric inpatient unit.MethodsNineteen patients sample, with an average age of 39.4 years old, diagnosed with schizophrenia, bipolar disorder or schizoaffective disorder. Patients inhaled loxapine 10 mg, using the staccato system, when they suffered a psychomotor agitation. The clinical efficacy was measured as a change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and in the Young Mania Rating Scale (YMRS) one hour after the administration of loxapine.ResultsA mean of 9.8 points reduction (22.6 at baseline and 12.7 one hour after the administration) was found on the PANSS-EC (t-test, P &lt; .001) and 68.4% of the patients were considered responders as they obtained a reduction of at least 40% of the basal score. On 10 of the total of the agitated patients showed an improvement of the psychomotor excitement, and this allowed the clinicians to remove the physical restraint; on 6 of the agitated patients the physical restraint could be avoided during the whole treatment; and 3 of the patients experienced a reduction of the excitement. The reduction on PANNS-EC on the latest group was not statistically significant (t-test, P = .121).ConclusionsInhaled loxapine was a non-invasive, rapid and effective alternative treatment for acute agitation in a psychiatric inpatient unit. It resulted more effective on mild and moderate cases; not been significantly effective on the severe cases of agitation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effect of aripiprazole lauroxil on agitation and hostility in patients with schizophrenia.

This study aimed to evaluate the effects of aripiprazole lauroxil on hostility and aggressive behavior in patients with schizophrenia. Patients aged 18-70 years with a diagnosis of schizophrenia and currently experiencing an acute exacerbation or relapse were randomized to intramuscular (IM) aripiprazole lauroxil 441 mg (n=207), 882 mg (n=208), or placebo (n=207) for 12 weeks. In post-hoc analyses, hostility and aggression were assessed by the Positive and Negative Syndrome Scale (PANSS) Hostility item (P7) and a specific antihostility effect was assessed by adjusting for positive symptoms of schizophrenia, somnolence, and akathisia. The PANSS excited component score [P4 (Excitement), P7 (Hostility), G4 (Tension), G8 (Uncooperativeness), and G14 (Poor impulse control)], and the Personal and Social Performance scale disturbing and aggressive behavior domain were also assessed. Of the 147 patients who received aripiprazole lauroxil 882 mg and with a baseline PANSS Hostility item P7 more than 1, there was a significant (P<0.05) improvement versus placebo on the PANSS Hostility item P7 score by mixed-model repeated-measures at the end of the study, which remained significant when PANSS-positive symptoms and somnolence or akathisia were included as additional covariates. The proportion with PANSS Hostility item P7 more than 1 at endpoint was significantly (P<0.05) lower with aripiprazole lauroxil versus placebo (53.6, 46.1, and 66.3% for 441, 882 mg, and placebo). A significant (P<0.05) improvement was found with aripiprazole lauroxil versus placebo for change from baseline in the PANSS excited component score. The proportion of patients with aggressive behavior on the Personal and Social Performance scale was significantly (P<0.05) lower for aripiprazole lauroxil: 30.0% for 441 mg versus 44.1% for placebo (P=0.006) and 22.2% for 881 mg (P<0.001 versus placebo). Treatment with aripiprazole lauroxil resulted in decreases in agitation and hostility in patients with schizophrenia and this antihostility effect appears to be independent of a general antipsychotic effect.

Intramuscular olanzapine for agitated patients: A systematic review and meta-analysis of randomized controlled trials

We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) of intramuscular (IM)-olanzapine (OLA-IM) versus controls in agitated patients. The risk ratio, number-needed-to-treat/harm, and standardized mean difference based on a random effects model were calculated. We identified 13 RCTs (19 comparisons) as follows: 7 comparisons with 1059 patients for OLA-IM versus placebo; 5 comparisons with 613 patients for OLA-IM versus haloperidol (HAL)-IM; 2 comparisons with 108 patients for OLA-IM versus ziprasidone (ZIP)-IM; 2 comparisons with 110 patients for OLA-IM versus HAL-IM plus midazolam; and 3 comparisons with 412 patients for OLA-IM versus HAL-IM plus promethazine, 2 comparisons with 355 patients for OLA-IM versus lorazepam-IM (LOR-IM); and 1 comparison with 67 patients for OLA-IM versus HAL-IM plus LOR-IM. OLA-IM was superior to placebo in both Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) and Agitation–Calmness Evaluation Scale (ACES) scores 2 h after first injection, and had a comparable side effect profile, including over sedation, extrapyramidal symptoms, akathisia, and anticholinergic use. While there was no significant difference in PANSS-EC scores after 2 h between OLA-IM and HAL-IM, OLA-IM outperformed HAL-IM in ACES after 2 h. Compared with HAL-IM, OLA-IM was associated with fewer side effects, including anticholinergic use, akathisia, extrapyramidal symptoms, and dystonia, and marginally less QT prolongation compared with HAL-IM. Based on our findings, OLA-IM is preferable to HAL-IM for the treatment of agitated patients. However, comparator data for ZIP-IM, LOR-IM and HAL-IM combination therapy were insufficient.

Antagonist and partial agonist at the dopamine D2 receptors in drug-naïve and non-drug-naïve schizophrenia: a randomized, controlled trial.

Few data are available on the efficacy and safety of antipsychotics with different dopamine D2 receptor (D2-R)-binding properties in drug-naïve and non-drug-naïve schizophrenia. Thus, we aimed to assess whether antipsychotic medication history influences efficacy and tolerability in schizophrenia, based on a randomized controlled study of antipsychotics with mechanisms involving either full antagonism or partial agonism of D2-R. Patients with schizophrenia were recruited and given perospirone or aripiprazole in a 12-week, flexible-dose, open-label, randomized controlled study. Data were analyzed after dividing the patients into antipsychotic-naïve and antipsychotic-treated group according to antipsychotic medication histories. Efficacy and safety were evaluated using the Positive and Negative Syndrome Scale (PANSS), the Drug-Induced Extrapyramidal Symptoms Scale, and the Barnes Akathisia Rating Scale. In patients receiving perospirone, the antipsychotic-naïve group (n = 22) showed greater symptom improvement than that shown by the antipsychotic-treated group (n = 29), as assessed by efficacy evaluation scales such as the PANSS total, positive, and excited component score (p = .006, p < .001, p = .003, respectively). In patients receiving aripiprazole, however, there was no significant difference in efficacy between the antipsychotic-naïve (n = 18) and antipsychotic-treated (n = 31) groups. No significant intra-group or inter-group difference was noted with respect to any of the tolerability-related parameters assessed. The present study data support the hypothesis that antipsychotic medication history may influence efficacy in patients who receive a D2-R full antagonist but not a D2-R partial agonist.

A single‐dose, randomized, double‐blind, placebo‐controlled trial of sublingual asenapine for acute agitation

To assess sublingual asenapine for acute agitation. Agitated adults 18-65 years (any diagnosis) presenting for treatment in an emergency department and found to have a score of ≥14 on the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) were randomized to receive either a single dose of a sublingual 10 mg tablet of asenapine or placebo. Primary outcome measure was change in the PANSS-EC score from baseline to 2 h after medication or placebo administration. Secondary outcomes included the percentage of responders with a ≥ 40% reduction from baseline on the PANSS-EC score at 2 h. A total of 120 subjects were randomized, 60 each to sublingual asenapine or placebo. Mean (SE) baseline PANSS-EC scores for the asenapine-treated and placebo-treated subjects were 19.4 ± 0.66 and 20.1 ± 0.61, respectively. Mean PANSS-EC scores at endpoint (LOCF) was 7.4 ± 0.65 for the asenapine-treated subjects and 14.7 ± 0.98 for the placebo-treated subjects. Change in PANSS-EC score at 2 h was statistically significantly greater for the asenapine-treated subjects compared with the placebo-treated subjects. NNT for response vs. placebo was 3 (95% CI 2-4). Sublingual asenapine was efficacious in the treatment of agitation with an effect size comparable to that observed in prior studies of intramuscular antipsychotics.