CGI-S Scores Research Articles

F115. INSIGHT AND MANIC SYMPTOMS IN PATIENTS WITH CHRONIC SCHIZOPHRENIA IN THE KOREAN COMMUNITY

BackgroundMany studies have highlighted the similarity of the symptoms between bipolar disorders and schizophrenia. Moreover, there are no pathognomonic symptoms that can differentiate these two disorders, and 9% of schizophrenia patients have experienced a manic syndrome in their lifetime. Insight about their symptoms and illness is very important factor for the differential diagnosis and the management in schizophrenia. To examine the relationship among the insight, the psychotic and manic symptoms, and clinical variables in patients with chronic schizophrenia.MethodsSeventy-four participants (male 44, female 30) with chronic schizophrenia in community mental health facilities have been evaluated with the Scale to assess Unawareness of Mental Disorder (SUMD), the Mood Disorder Questionnaire (MDQ), and the Brief Psychiatric Rating Scale (BPRS).ResultsThe mean number of previous admission was 3.85. Their drug adherence was favorable (6.73 day/week). Mean CGI-S score was 3.8. Thirty-five percent of subject were MDQ positive (cutoff point = 7 or more). Among SUMD, “awareness of effect of medication” showed significant negative correlation (r = -0.33) with total MDQ score not with total BPRS score. The negative correlation was more obvious in participants with negative MDQ (total MDQ score 6 or less, r = -0.31). Several MDQ items (irritability, r = -0.25; decreased sleep, r = -0.27; thought racing, r = -0.28; and easy distractibility, r = -0.40) negatively correlated with “awareness of effect of medication”. In contrast, only one item (guilt feeling, r = -0.27) of BPRS revealed this correlation. Individual items in MDQ and BPRS rarely correlated with each other. Total MDQ score was not correlated with duration of illness and medication adherence.DiscussionManic symptoms were frequently detected even in schizophrenia as reported in previous studies. This made it difficult to differentially diagnose the disorder using only the total MDQ score. There was possible relationship between these manic symptoms and their insight. Identifying manic symptoms in schizophrenia would be considerable in clinical setting.

Clinical improvement, relapse and treatment adherence with paliperidone palmitate 1-month formulation: 1-year treatment in a naturalistic outpatient setting

Purpose: To evaluate paliperidone palmitate 1-month formulation (PP1M) effectiveness in a naturalistic outpatient psychiatric setting.Materials and methods: We collected data from 50 outpatients affected by schizophrenia disorders treated with PP1M for 12 months in an Italian Mental Health Department. After analyzing selected demographic, clinical and pharmacological variables, we performed mirror analysis to compare psychiatric hospitalizations and urgent consultations required by the same patient 6 and 12 months before and after PP1M implementation (primary outcome). We analyzed clinical improvement in symptom (Clinical Global Impression-severity and improvement) and functioning (Global Assessment of Functioning) scales and drop-out rate during the 12-month PP1M treatment (secondary outcome). Data were statistically analyzed.Results: The mean PP1M dose was 93.5 mg (±27.7 SD) with a mean interval between each injection of 27.1 d (±4.5 SD). Twenty-three patients (46%) reported adverse effects (sexual dysfunctions, weight gain and extrapyramidal symptoms).Fifteen patients (30%) dropped out after 137.2 d (±103.1 SD) on average: six due to the lack of therapeutic adherence, six due to inefficacy and three due to adverse events. The drop-out patients presented more severe clinical profile in CGI-S and GAF scores at T0 in comparison with others. At mirror analysis, 12-month but not 6-month PP1M treatment statistically significantly reduced psychiatric hospitalizations (t = 2.3, p < .05) and urgent consultations (t = 2.1, p < .05). Both scale scores showed statistically significant improvement at T12 in comparison to T0.Conclusions: This naturalistic study indicates that long-term PP1M treatment was safe and effective in preventing hospitalizations and urgent consultations as well as in improving clinical course.

What kinds of factors affect the academic outcomes of university students with mental disorders? A retrospective study based on medical records.

University students that suffer from mental disorders seem to have difficulty graduating. Therefore, we investigated risk and protective factors of dropping out with the aim of improving such students' academic outcomes. First, we statistically compared the academic outcomes of 203 undergraduate students who received treatment in the Department of Psychiatry of the Tsukuba University Health Center to those of matched controls. Second, clinical factors of 370 mentally ill students were statistically compared between the dropout and graduate groups. Mentally ill students experienced significantly greater difficulties graduating. Furthermore, the ratio of females and the year of study at initial consultation were significantly lower in the dropout group. However, duration of illness, social withdrawal, temporary leaves of absence, percentage of diagnosis of F2, history of truancy, CGI-S/GI score, number of suicide attempts, visits to us, family consultations with us and grade repeating were longer or greater in the dropout group. Ultimately, the number of suicide attempts, CGI-S score, social withdrawal and leaves of absence were significantly associated with dropping out. Moreover, duration of social withdrawal and leaves of absence were significantly correlated with CGI-GI score. We found that the number of suicide attempts, CGI-S score, social withdrawal and extended enrollment were risk factors for dropping out, while the therapeutic effect seemed to be a protective factor. As risk factors involved states of social maladjustment, it is necessary not only to treat mental disorders, but also to provide assistance such as educational and individual support for daily living.

Efficacy of Lisdexamfetamine in Adults With Moderate to Severe Binge-Eating Disorder

The ability of pharmacotherapies to prevent relapse and maintain efficacy with long-term treatment in psychiatric conditions is important. To assess lisdexamfetamine dimesylate maintenance of efficacy in adults with moderate to severe binge-eating disorder. A multinational, phase 3, double-blind, placebo-controlled, randomized withdrawal study including 418 participants was conducted at 49 clinical research study sites from January 27, 2014, to April 8, 2015. Eligible adults met DSM-IV-R binge-eating disorder criteria and had moderate to severe binge eating disorder (≥3 binge-eating days per week for 14 days before open-label baseline; Clinical Global Impressions-Severity [CGI-S] scores ≥4 [moderate severity] at screening and open-label baseline). Following a 12-week, open-label phase (dose optimization, 4 weeks [lisdexamfetamine dimesylate, 50 or 70 mg]; dose maintenance, 8 weeks), lisdexamfetamine responders (≤1 binge eating day per week for 4 consecutive weeks and CGI-S scores ≤2 at week 12) were randomized to placebo or continued lisdexamfetamine during a 26-week, double-blind, randomized withdrawal phase. Lisdexamfetamine administration. The primary outcome variable, time to relapse (≥2 binge-eating days per week for 2 consecutive weeks and ≥2-point CGI-S score increases from randomized withdrawal baseline), was analyzed using a log-rank test (primary analysis); the analysis was stratified for dichotomized 4-week cessation status. Safety assessments included treatment-emergent adverse events. Of the 418 participants enrolled in the open-label phase of the study, 411 (358 [87.1%] women; mean [SD] age, 38.3 [10.4] years) were included in the safety analysis set. Of 275 randomized lisdexamfetamine responders (placebo, n = 138; lisdexamfetamine, n = 137), the observed proportions of participants meeting relapse criteria were 3.7% (5 of 136) for lisdexamfetamine and 32.1% (42 of 131) for placebo. Lisdexamfetamine demonstrated superiority over placebo on the log-rank test (χ21, 40.37; P < .001) for time to relapse; the hazard ratio, based on a Cox proportional hazards model for lisdexamfetamine vs placebo, was 0.09 (95% CI, 0.04-0.23). The treatment-emergent adverse events observed were generally consistent with the known profile of lisdexamfetamine. Risk of binge-eating relapse over 6 months was lower in participants continuing lisdexamfetamine than in those randomized to placebo. The hazard for relapse was lower with lisdexamfetamine than placebo. clinicaltrials.gov Identifier: NCT02009163.

Effectiveness of long-term vortioxetine treatment of patients with major depressive disorder

To investigate the effectiveness, safety, and tolerability of vortioxetine in patients treated at therapeutic doses (5–20mg/day) for both acute and maintenance treatment, patient-level data were pooled from 5 long-term (52-week), open-label extension studies of major depressive disorder. The mean (±standard deviation) MADRS total score improved from 17.1±10.2 at the start of maintenance therapy to 7.6±8.2 (observed cases [OC]) or 10.3±9.9 (last observation carried forward [LOCF]) at week 52. The mean HAM-A total scores improved from 11.3±6.9 to 6.0±6.0 (OC) or 7.5±6.7 (LOCF) and the mean CGI-S score improved from 3.11±1.20 to 1.94±1.08 (OC) or 2.27±1.26 (LOCF) at week 52. Response and remission rates increased over time. At week 52, the total response rate was 75.4% (n=916/1215, LOCF) and the total remission rate was 60.7% (n=738/1215, LOCF). There were no differences in effectiveness as assessed by MADRS total scores at week 52 in subgroups based on gender, age (<55 vs ≥55 years), baseline HAM-A total score (<20 vs ≥20), baseline MADRS total score (<30 vs ≥30), previous major depressive episodes (MDEs) (<3 vs ≥3) or current MDE duration (<6 vs ≥6 months) at the start of the lead-in studies, or response status (≥50% decrease in MADRS total score during the lead-in study). The most commonly reported adverse event during the maintenance period was nausea.

Treatment with risperidone vs. olanzapine in naturalistic study of bipolar manic inpatients

IntroductionThere are very few comparative controlled trials of risperidone versus olanzapine in manic patients. No previous naturalistic study has compared the efficacy of these two antipsychotics in the natural environment of manic inpatients.ObjectiveThe aim of this retrospective and naturalistic study was to evaluate the efficacy of acute treatment with risperidone vs. olanzapine in Bipolar I manic inpatients.Methods(1) Patients: the study includes all the inpatients diagnosed with bipolar I manic episode (DSM-IV) who were admitted during the years 2009 to 2014. Patients treated with risperidone and olanzapine concomitantly (n = 6) and patients not treated with risperidone or olanzapine (n = 129) were excluded.The patients finally included (n = 183) were separated in two groups:– treated with risperidone (n = 89);– treated with olanzapine (n = 94).(2) The Student-T test was used to compare, between the groups, the mean of scores in YMRS and CGI-S scales and the mean of length of stay.ResultsBaseline characteristics were similar between the groups. The majority of patients were also treated with mood stabilizers (46% with lithium and 45% with valproate).The mean decrease in CGI-S scores from baseline to the day of discharge was significantly (P &lt; 0.003) higher in the risperidone group (−2.81 vs. −2.36). The length of stay was significantly (P &lt; 0.004) lower in the olanzapine group (mean of 23.03 days vs. mean of 30.3).Conclusions(1) The CGI-S scores in manic patients treated with risperidone decreased more than in patients treated with olanzapine during admission. (2) The length of stay was significantly lower in patients treated with olanzapine.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Correlations between doctors’ and patients’ assessment of depression’ severity and efficacy of treatment

IntroductionData on accordance and clinical significancy of objective (doctor, psychometric scales) and subjective (patient with depression) assessment of severity of depression are almost lacking. Aim of the multicenter study “EMOTION” was to compare prognostic value of doctor's and patient's assessment of depressive symptoms severity as for its grading and treatment outcome.MethodStudy sample consist of 107 depressive patients. The study used clinical and psychometric (HDRS, SHAPS, CGI-S, CGI-I, PGI-S, PGI-I, Visual Analog Scale) methods.ResultsOur data suggest that there's statistically significant (Р ˂ 0.001) discrepancy between doctors’ (CGI-S) and patients’ (PGI-S) assessment of depressive symptoms’ severity at first visit. Concordant opinions were found only in “marked depression” (37.49% of doctors and 36.59% of patients) and in “borderline depression” (4.79% of doctors and 3.79% of patients). Otherwise, doctors’ and patients’ opinions were discordant. Doctors’ scores were more extreme (severe and extremely severe depression); patients’ scores were more “moderate”. We have found inconsistence between HDRS and CGI-S scores. In the course of reduction of depression severity during antidepressive treatment (agomelatine) doctors’ and patients’ scores were more and more in line with each other.ConclusionWe have found leveling of prognostic value of psychometric assessment of depression severity by doctors and patients (in terms of reduction of depressive symptoms severity and treatment outcome) during antidepressive therapy. It is possible that in some HDRS items scores were overestimated.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A scale of autonomy for patients with schizophrenia – new instrument for clinical assessment of the level of independency: Description and validation

IntroductionToday the scales for measurement of functional status and life satisfaction (GAF, PSP, EQ-5D, SQLS) gain more importance in assessing schizophrenic patients. Autonomy of living is to the great extent the basis of patient well-being. Each of these scales has the criteria, testing ability for independent life, but none of it tests autonomy as a separate object.ObjectiveDevelopment of a new scale.AimsDescription and validation of a scale for evaluation of autonomy of living in schizophrenic patients.MethodsForty patients diagnosed with schizophrenia according to ICD−10 (F 20.хх), 13 males and 27 females, aged 49.8 ± 9, disease duration is 22 ± 8.6 years. New scale and PANSS, CGI-S, NSA, BACS, GAF, PSP was administered.ResultsThe scale comprises five points (activity, intentional behavior, range of social interaction, specificity of interaction with the doctor (medical conventionality) and autonomy), and total score. The internal consistency of the scale was high – cronbach's alpha 0.83. The construct validity with GAF and PSP was moderate (R varied from 0.36 to 0.55). The total score of the new scale correlated with the PANSS negative subscale score (R = −0.51), with CGI-S score (R = −0.57), and with the BACS total score (R = −0.57).ConclusionThe scale of autonomy corresponds to the major psycho-diagnostic requirements: internal consistency, construct and discriminative validities. It can be considered a new instrument for assessing the integrative target of treatment and rehabilitation of patients with schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

SA105. Characteristics of Patients With Recent-Onset Schizophrenia and Their Caregivers: Is There a Correlation With Caregiver Burden?

Abstract Schizophrenia is a chronic, serious mental illness (SMI) that affects approximately 1.1% of the population aged ≥18 years. There are approximately 8.4 million caregivers of US adults with SMI. Caregivers can provide vital support, but the burden and distress caused by recurrent SMI symptomatology are barriers to effective caregiving. The aim of this analysis is to describe the demographic and baseline characteristics of caregivers and patients with recent-onset schizophrenia, schizoaffective disorder, or schizophreniform disorders enrolled in the Family Intervention in Recent-Onset Schizophrenia Treatment (FIRST) study (NCT02600741) and evaluate the correlation between caregiver burden and severity of patient illness. FIRST is a 12-month, ongoing, prospective, randomized study to evaluate the effect of a caregiver-directed psychosocial intervention on outcomes in patients with recent-onset schizophrenia, schizoaffective disorder, or schizophreniform disorders receiving paliperidone palmitate (PP) or oral antipsychotic treatment (OAT). The caregivers were randomized into 2 study groups (usual caregiver support or study-provided caregiver-directed psychosocial intervention) within strata defined by the type of antipsychotic medication (PP or OAT) that patients were prescribed by their treating physicians. The patients were assessed for symptom severity (CGI-S) and illness management and recovery. The caregivers were assessed for caregiver burden (IEQ), general health (SF-12), and health-care resource utilization. The study is ongoing and the current analysis is based on interim data from 52 patient–caregiver pairs. Patients were predominantly male (84.6%), were white (57.6%), black (36.5%), and had a mean age of 25.3 years; 9.6% were Hispanic. Most (88.5%) patients lived at home with family or friends. The average CGI-S score for patients receiving PP was 4.94 and for patients receiving OAT was 3.89. Caregivers were predominantly female (76.9%), were mostly parents (86.5%), and had a mean age of 52.4 years. There was a moderate yet significant correlation between the IEQ total score and patients’ CGI-S score at baseline ( = .36, = .011). The correlation between the total IEQ score and the patient’s or caregiver’s age, gender, and race was not significant. The interim analysis of the baseline data showed that greater severity of patient illness is correlated with higher caregiver burden.Reference 1. National Alliance for Caregiving. www.caregiving.org. 2016. Accessed October 11, 2016.

SU14. Characteristics Associated With Relapse in Patients With Schizophrenia: Post Hoc Analysis of a Randomized, Double-Blind, Placebo-Controlled, Cariprazine Relapse Prevention Trial

Background: Relapse is common in schizophrenia; identifying characteristics associated with relapse may help improve disease management. Cariprazine, a D3/D2 receptor partial agonist, is approved in the United States for the treatment of schizophrenia. Post hoc analyses of a long-term, randomized, double-blind (up to 72 weeks), relapse prevention trial ({type:clinical-trial,attrs:{text:NCT01412060,term_id:NCT01412060}}NCT01412060) were performed to identify characteristics associated with relapse in placebo- and cariprazine-treated patients. Methods: Baseline characteristics in cariprazine-treated (3, 6, or 9 mg/d) or placebo-treated patients were evaluated in relation to relapse status. Demographic variables included age, sex, race, weight, and BMI. Psychiatric history variables included mean age at illness onset, duration of schizophrenia, duration of current episode, number of lifetime psychotic episodes, previous hospitalizations, and acute exacerbations in the past year. Baseline rating scale severity scores (eg, Positive and Negative Syndrome Scale [PANSS] and Clinical Global Impressions-Severity [CGI-S]) were evaluated. Differences in demographic and psychiatric history variables were evaluated using the Student t test (categorical variables) or Fisher exact test (continuous variables); rating scale severity scores were evaluated with 2-way ANOVA with relapse and study center as factors. Results: Relapse occurred in nearly twice as many placebo-treated (47.5%) as cariprazine-treated patients (24.8%) (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). For cariprazine-treated patients who relapsed vs those who did not, significant differences were seen in baseline age (mean, 43 vs 38 y), weight (85 vs 73 kg), BMI (29 vs 26 kg/m2), and race (all, P < .05); for placebo-treated patients, there were no significant differences in demographic variables based on relapse status. In both treatment groups, patients who relapsed vs patients who did not relapse had a greater mean number of previous hospitalizations (cariprazine = 8.4 vs 4.3 [P = .0199]; placebo = 4.9 vs 2.8 [P = .0183]). Cariprazine patients who relapsed vs those who did not had longer illness duration (18.1 y vs 9.9 [P = .0005]); the number of lifetime episodes also differed by relapse status (P = .0016), with a greater percentage of relapsed patients experiencing ≥5 episodes. Baseline PANSS total score and CGI-S scores were not significantly different in relapsed vs nonrelapsed patients in either treatment group. Conclusion: While patients treated with cariprazine had a lower rate of relapse than placebo overall, the results suggest that patients who were older, heavier, or had a later stage of illness may be more prone to relapse during cariprazine treatment. In patients randomized to placebo, demographic characteristics and psychiatric history were not as meaningful in predicting relapse. Greater symptom severity at baseline did not appear to be associated with relapse.

Positive changes in the severity of residual psychotic symptoms in schizophrenic patients switched to treatment with risperidone

To evaluate the effect of changing therapy from typical antipsychotics to the atypical antipsychotic risperidone in the treatment of difficult-to-treat residual psychotic symptoms. The study included 15 patients, 8 men and 7 women, mean age 49.1±10.25 years, diagnosed with paranoid schizophrenia, partial remission (ICD-10 F20.04). At the beginning all participants received regular maintenance antipsychotic therapy with typical antipsychotics. The patient assessment with the PANSS, CGI scale and GAF scale was performed at the beginning (before the change of antipsychotics to risperidone) and in the end of the study. The primary efficacy endpoint was a reduction in scores on the PANSS items P1 'delusions' and P3 'hallucinatory behavior' to 1 (no such symptom) or 2 (minimal residual symptom). Secondary criteria were positive changes in the severity of other psychopathological symptoms and an increase in the social functioning level. The average dose of risperidone was 4.62±1.35 mg. The duration of treatment was 2 month. After switching from typical antipsychotics to risperidone and two months monotherapy, there were significant positive changes in the total PANSS score as well as in positive subscale score and CGI-S score. The small, but statistically significant, changes were detected in the overall functioning of the patients (the increase in the GAF score). The dynamics of residual psychotic symptoms was unequal: the severity of hallucinatory symptoms decreased significantly while the delusional symptoms remained unchanged. The authors suggest that excessive dopaminergic blockade might play a significant role in the pathogenesis of residual symptoms. This fact may explain the positive effect of treatment in the cases with the less degree of dopaminergic blockade. If it is true, the treatment strategy in the maintenance phase should not be a direct continuation of acute phase therapy and switching to other drugs and changing of the dose are needed.

Successful Treatment Response with Aripiprazole Augmentation of SSRIs in Refractory Obsessive–Compulsive Disorder in Childhood

The aim of this study is to evaluate the aripiprazole augmentation of selective seratonine reuptake inhibitors (SSRIs) in children and adolescents with treatment-resistant OCD. Forty-eight children and adolescents (14 girls, 34 boys), who are non-responders to treatment with at least two types of SSRIs and CBT, were administered a 12-week of augmentation. Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I) sub-scales were used for evaluation of the treatment outcomes. The results showed that total CY-BOCS scores were decreased from 33.3 ± 7.5 to 11.7 ± 9.3 (p < 0.001), CGI-S scores decreased from 6.3 ± 0.9 to 2.7 ± 1.6 (p < 0.001), and CGI-I scores improved from 4.3 ± 0.6 to 2.2 ± 1.1 (p < 0.001). Sensitivity analyses in 29 patients without SSRI dose escalation along with aripiprazole augmentation have also revealed that improvement effect was still significant, and CY-BOCS scores were improved from 34.2 ± 7.9 to 13 ± 10.3, CGI-S improved from 6.4 ± 1.0 to 3.0 ± 1.7, and CGI-I improved from 4.4 ± 1.0 to 2.3 ± 1.1 (p < 0.001 for all). Analyses revealed that a significant clinical improvement has been observed with aripiprazole augmentation. Aripiprazole augmentation of SSRIs is a promising strategy in the management of treatment-refractory OCD children and adolescents.

P.3.b.036 - Discrepancies between the PANSS and CGI-S scores at baseline are a marker for subsequent data quality issues in schizophrenia clinical trials

Remission and response were suggested as the most relevant outcome criteria for the treatment of depression. There is still marked uncertainty as to what cut-offs should be used on current depression rating scales. The goal of the present study was to compare the validity of different HAMD, MADRS and BDI cut-offs for response and remission.The naturalistic prospective study was performed in 12 psychiatric hospitals in Germany. All evaluable patients (n = 846) were hospitalized and had to meet DSM-IV criteria for major depressive disorder. Biweekly ratings were assessed using HAMD-21, MADRS and BDI. A CGI-S score of 1 and a CGI-I score of at least 2 was used as the primary comparative measure of remission and response, respectively.A HAMD-21 cut-off ≤ 7 (AUC: 0.92), HAMD-17 cut-of ≤ 6 (AUC: 0.90), MADRS cut-off ≤ 7 (AUC: 0.94) and BDI cut-off ≤ 12 (AUC: 0.83) were associated with a maximum of specificity and sensitivity for defining remission.A minimum decrease of 47% of the HAMD-21 (AUC: 0.90), ≤57% for HAMD-17 (AUC: 0.89), ≤ 46% for MADRS (0.91) and a decrease of 47% for the BDI baseline score (AUC: 0.78) best corresponded CGI response criteria.Our data largely confirmed currently used remission and response criteria in naturalistically treated patients.

An interventional, multi-center, randomized, double-blind, placebo-controlled, active reference, flexible dose study of brexpiprazole in adults with acute schizophrenia

IntroductionBrexpiprazole is a serotonin-dopamine activity modulator that is a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.ObjectivesEvaluating the efficacy, safety, and tolerability of flexible doses of brexpiprazole compared with placebo in patients with acute schizophrenia.AimPrimary endpoint was change from baseline to week 6 in PANSS total score and key secondary endpoint was change from baseline to week 6 in CGI-S score.MethodsPhase 3, multi-center, randomized, double-blind, placebo-controlled, active reference, trial (NCT01810380). Hospitalized patients were randomized to brexpiprazole (2 to 4 mg/day), placebo, or quetiapine extended release (400 to 800 mg/day) for 6 weeks. Quetiapine was included as an active reference. Changes from baseline were analyzed using an MMRM approach.ResultsMean change in PANSS total score was −20.0 and −15.9 in the brexpiprazole (n = 150) and placebo (n = 159) groups, respectively (P = 0.056). Sensitivity analyses suggested treatment effect (e.g., ANCOVA, LOCF: P = 0.025; ANCOVA, OC: P = 0.026). Mean change in PANSS total score (−24.0) with quetiapine (n = 150) was significantly greater than that with placebo (P &lt; 0.001), demonstrating sensitivity of the assay. Brexpiprazole separated from placebo on the mean change in CGI-S score (−1.2 vs. −0.9, P = 0.014). The proportion of patients reporting TEAEs were similar between the brexpiprazole and placebo treatment groups (54% versus 54.7%).ConclusionTreatment with brexpiprazole showed a clinically meaningful improvement in patients with acute schizophrenia. While the difference between brexpiprazole and placebo only approached statistical significance, sensitivity analyses and secondary endpoints supported a treatment effect of brexpiprazole.Disclosure of interestThe authors have not supplied their declaration of competing interest.

AZD8529, a positive allosteric modulator at the mGluR2 receptor, does not improve symptoms in schizophrenia: A proof of principle study

IntroductionActivation of metabotropic glutamate (mGluR2/3) receptors has been proposed as an alternative mechanism to dopaminergic-based antipsychotics to correct glutamatergic deficits hypothesized to underlie schizophrenia symptoms. This study investigates the efficacy and safety of AZD8529, a selective positive allosteric modulator (PAM) at the mGlu2 receptor, in symptomatic patients with schizophrenia. MethodsPatients were randomized to receive AZD8529 40mg, risperidone 4mg, or placebo as monotherapy. Treatment lasted for 28days, and clinical efficacy was assessed using Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) scores. ResultsThere were no significant differences between patients treated with AZD8529 versus placebo in change from baseline to endpoint in PANSS total, negative and positive symptom subscale, or CGI-S scores. In contrast, risperidone demonstrated significant efficacy relative to placebo. ConclusionThese results do not support a role for the mGluR-2 PAM AZD8529 as an antipsychotic and indicate that positive modulation of mGluR type 2 receptors alone is not sufficient for antipsychotic effects in acutely ill schizophrenia patients.

Evaluation of the contribution of inpatient services and experiences on improvement in child and adolescent psychiatry practice

Objective: In this study it’s aimed to evaluate the sociodemographic characteristics, psychiatric diagnoses, treatment options and improvement levels of the patients who were treated in Child and Adolescent Psychiatry inpatient service. Methods: One hundred and forty-nine patients between who were treated in Ege University Child and Adolescent Psychiatry inpatient service between March 2013 and September 2014 were evaluated. The patients’ files were used for data collection and Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime version (K-SADS) was used for appropriate patients. Clinic Global Impression Scale-Severity (CGIS-S) was used for all cases for determining the psychiatric disorder severity and Clinic Global Impression Scale-Improvement (CGIS-I) was used for evaluating the treatment effect. Results: The age mean was 14.2. %63.1 of the patients were girls and %36.9 boys. The common diagnoses were mood disorders %57.7, attention deficit and hyperactivity disorder %10.7, schizophrenia and other psychotic disorders %8.1. The mean treatment duration was 24.4 days. It is founded that the longer duration of hospitalization has positive effect on CGI improvement scores. All patients get psychopharmacological medication during inpatient follow up. The most used medication were antipsychotics. First CGIS-S median level of the patients was 5 (markedly ill) (range: 3-7) and 3 when discharging. When we compare the hospitalization and discharge CGI-S score medians of patients’, a statistically significant difference was founded. Results: Although there is a limited number of inpatient services for children, the positive contribution of inpatient services on children and adolescents’ mental health is incontrovertible unquestionable. This study is a preliminary report for forthcoming studies with special inpatient services for children and adolescent. Key words:

Diagnostic performance of increased prolidase activity in schizophrenia

We investigated whether prolidase activity has a diagnostic test value in schizophrenia and assessed the relation between prolidase activity and sociodemographic-clinical characteristics of patients with schizophrenia. Fifty patients with schizophrenia (diagnosed as schizophrenia according to DSM-V criteria) and 50 healthy volunteers were included in this study. Case and control groups had a similar distribution in age, sex, body mass index (BMI), and smoking status. Serum prolidase activity was measured in both groups and was determined to be significantly higher in the patient group (509.706±41.918) compared to the control group (335.4±13.6; t=6.231; p=0.0001). A cut-off point of 392.65U/L prolidase was determined for diagnostic measures from the plotted ROC curve. The area under the ROC curve was 1.000, which was significant (p<0.0001). Higher values were assigned as the disease state. Both positive predictive value (PPV) and negative predictive value (NPV) were 100% at the cut-off point of 392.650U/L. The prolidase levels of the control group were all below the cut-off point. There were no statistically significant differences between the two groups with regard to age, gender, or BMI (p>0.05), and no correlation was found between mean prolidase activity and age of onset of the disease, family history, disease duration, number of hospitalizations, subtypes of schizophrenia, PANSS scores or sub-scores, CGI-S scores, S-A scale scores, and the antipsychotic treatment (p>0.05). The results of this study indicate that serum prolidase activity may be a useful diagnostic test for schizophrenia; however, further studies are needed to verify this.

Lurasidone for the Treatment of Major Depressive Disorder With Mixed Features: A Randomized, Double-Blind, Placebo-Controlled Study

Accumulating evidence indicates that manic symptoms below the threshold for hypomania (mixed features) are common in individuals with major depressive disorder. This form of depression is often severe and is associated with an increased risk for recurrence, suicide attempts, substance abuse, and functional disability. This study evaluated the efficacy and safety of lurasidone in major depressive disorder with mixed features. Patients meeting DSM-IV-TR criteria for major depressive disorder who presented with two or three protocol-defined manic symptoms were randomly assigned to 6 weeks of double-blind treatment with either lurasidone at 20-60 mg/day (N=109) or placebo (N=100). Changes from baseline in Montgomery-Åsberg Depression Rating Scale score (MADRS; primary outcome measure) and Clinical Global Impressions severity subscale score (CGI-S; key secondary outcome measure) were evaluated using a mixed model for repeated-measures analysis. Lurasidone significantly improved depressive symptoms and overall illness severity, assessed by least squares mean change at week 6 in the MADRS and CGI-S scores: -20.5 compared with -13.0 (effect size, 0.80) and -1.8 compared with -1.2 (effect size, 0.60), respectively. Significant improvement in manic symptoms, assessed by the Young Mania Rating Scale, was also observed, in addition to other secondary efficacy endpoints. Rates of discontinuation due to adverse events were low. The most common adverse events were nausea (6.4% and 2.0% in the lurasidone and placebo groups, respectively) and somnolence (5.5% and 1.0%). Lurasidone was effective and well tolerated in this study involving patients with major depressive disorder associated with subthreshold hypomanic symptoms (mixed features).

Patterns of long-term and short-term responses in adult patients with attention-deficit/hyperactivity disorder in a completer cohort of 12 weeks or more with atomoxetine

BackgroundAtomoxetine is a well-established pharmacotherapy for adult ADHD. Long-term studies show incremental reductions in symptoms over time. However, clinical experience suggests that patients differ in their response patterns. MethodsFrom 13 Eli Lilly-sponsored studies, we pooled and analyzed data for adults with ADHD who completed atomoxetine treatment at long-term (24weeks; n=1443) and/or short-term (12weeks; n=2830) time-points, and had CAARS-Inv:SV total and CGI-S data up to or after these time-points and at Week 0 (i.e. at baseline, when patients first received atomoxetine). The goal was to identify and describe distinct trajectories of response to atomoxetine using hierarchical clustering methods and linear mixed modelling. ResultsBased on the homogeneity of changes in CAARS-Inv:SV total scores, 5 response clusters were identified for patients who completed long-term (24weeks) treatment with atomoxetine, and 4 clusters were identified for patients who completed short-term (12weeks) treatment. Four of the 5 long-term clusters (comprising 95% of completer patients) showed positive trajectories: 2 faster responding clusters (L1 and L2), and 2 more gradually responding clusters (L3 and L4). Responses (i.e.≥30% reduction in CAARS-Inv:SV total score, and CGI-S score≤3) were observed at 8 and 24weeks in 80% and 95% of completers in Cluster L1, versus 5% and 48% in Cluster L4. ConclusionsWhile many adults with ADHD responded relatively rapidly to atomoxetine, others responded more gradually without a clear plateau at 24weeks. Longer-term treatment may be associated with greater numbers of responders.

A controlled trial of quetiapine XR coadministration treatment of SSRI-resistant panic disorder.

BackgroundOpen-label quetiapine coadministration with SSRI therapy, in a diagnostically mixed sample of comorbid anxiety patients, offered additional anxiolytic benefit. Therefore, we designed the following controlled trial to confirm these findings in a comorbid, SSRI-resistant, panic disorder (PD) patient sample.MethodsThis was a single-site, double-blind, placebo-controlled (PLAC), randomized, parallel group (2 groups), 8-week, quetiapine extended release (XR) coadministration trial. SSRI resistance was determined either historically or prospectively. Patients were randomized if they remained moderately ill (CGI-S score ≥ 4). Change in the PDSS scale total score was the primary efficacy outcome measure. Responders were identified as those with a ≥50 % decrease from their baseline PDSS score. In the early weeks of therapy, XR was flexibly and gradually titrated from 50 to 400 mg/day.Results43 patients were screened in total, and 26 of these were randomized and evaluable. 21 patients (78 % of the randomized group) completed the trial (10 XR; 11 PLAC). The endpoint quetiapine XR mean daily dose ± SD was 150 ± 106 mg. While, in the sample as a whole, there was improvement in PDSS scores across the 8-week trial (ANOVA main effect of time, F = 10.9, df8,192, p < 0.0001), the treatment × time interaction effect was not statistically significant (F = 0.8, df8,192, p = 0.61). There was no between-group difference in responder frequency at endpoint.ConclusionsThis proof-of-concept RCT did not support the efficacy of this treatment strategy for SSRI-resistant PD. Quetiapine XR was generally well-tolerated. Important limitations were the small sample size, and the relatively low average dose of quetiapine XR used.ClinicalTrials.gov ID#: NCT00619892