Clinical Global Impressions-Severity Of Illness Research Articles

Fluoxetine in the Management of Major Depressive Disorder in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials.

Fluoxetine is a serotonin-specific reuptake inhibitor antidepressant and is the only approved pharmacological treatment for major depressive disorder (MDD) in children and adolescent. We searched the published randomized controlled-trials to review fluoxetine efficacy and tolerability using the databases PubMed, EudraCT, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for fluoxetine role in managing MDD in children and adolescents. A meta-analysis was conducted using the identified 7 clinical trials to assess efficacy using the outcomes: Children's Depression Rating Scale-Revised (CDRS-R), Clinical Global Impressions-Severity of Illness (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) response rate. The risk of discontinuation due to adverse effects and common side effects were examined. The mean difference in change from baseline for CDRS-R was -2.72 (95% confidence interval [CI], -3.96, -1.48) favoring fluoxetine treatment (P < .001). Similarly, mean difference for CGI-S was -0.21 (95% CI, -0.36, -0.06). The risk ratio (RR) of discontinuing due to adverse events was 0.98 (95% CI, 0.54, 1.83), with RR for headache side effects 1.34 (95% CI, 1.03, 1.74) and rash 2.6 (95% CI, 1.32, 5.14). Fluoxetine demonstrates significant improvements in symptom intensity control in young patients suffering from MDD and is considered well tolerated with similar rates of trials discontinuation; however, fluoxetine was associated with a higher risk of headache and rash side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting the care of young mental health patients.

T217. MEDICATION ADHERENCE AND ITS CORRELATES AMONG PATIENTS WITH RECURRENT SCHIZOPHRENIA: A LARGE-SCALE STUDY IN CHINA

BackgroundThe Medication Adherence Rating Scale (MARS) is a rapid, non-intrusive way of measuring adherence to medication in order to improve management of patients with schizophrenia. The current study evaluated the reliability of the Chinese (Mandarin) version of the MARS and explored clinical and demographic correlates to medication adherence in a large sample of patients with recurrent schizophrenia in China.Methods1198 patients with recurrent schizophrenia were recruited from 37 different hospitals in 17 provinces/municipalities of China and evaluated with the Medication Adherence Rating Scale (MARS), Clinical Global Impression-Severity of illness (CGI-S) and Sheehan Disability Scale-Chinese version (SDS-C). Socio-demographic data included gender, age, marital status, education level, employment status and living with others or alone. Clinical data included duration of illness, number of relapses, and medication use, as well as current stage of disease evaluated by SCID. Pearson correlations were used to examine associations between MARS, socio-demographic, and clinical characteristics. Independent sample T-tests were used to compare MARS score between different socio-demographic and clinical characteristics. Finally, a cut-off score of 6 on the MARS (ranged from 1 to 10) was used to divide the sample into two groups (i.e. MARS score≥ 6 identified good adherence and MARS score< 6 indicated poor adherence). Bivariate logistic regression models with the two groups (MARS score<6 and MARS score≥6) as the dependent variable was used to identify influencing factors of medication adherence. Data processing and analyses were conducted on SPSS 22.0 and Mplus 7.4.ResultsThe MARS showed good internal consistency and psychometric properties. MARS outcomes varied by demographic and clinical characteristics; only 28.5% recurrent schizophrenia patients met the criteria of good adherence to antipsychotic medication. Findings indicated older age (OR=1.04, 95%CI=1.02–1.06), unsteady income (OR=1.79, 95%CI=1.29–2.49), acute period (OR=4.23, 95%CI=3.21–5.59) and a higher CGI-S score (OR=1.44, 95%CI=1.03–2.01) had significantly predictive effects on poor medication adherence. MARS demonstrated good reliability in our sample (Cronbach’s α =0.83; Spearman-Brown = 0.72).DiscussionThis study of the MARS is unique for a few reasons. First, comparative reports on MARS use in mainland China have not been published internationally; similar tests on reliability and correlation have only been reported in Hong Kong and Taiwan (Hui et al., 2006; Kao and Liu, 2010). Second, in considering demographic and clinical correlates of medication adherence in patients with recurrent schizophrenia, our MARS study broadly represents China with 17 of 27 provinces/municipalities reporting data from multiple geographic regions, with the participation of hundreds of psychiatrists across China.Only 28.5% recurrent schizophrenia patients met the criteria of good adherence to antipsychotic medication in this study. Low levels of good medication adherence in schizophrenia patients are found across Asia, with 27% in Korea meeting the criteria of good adherence (Kim et al., 2006) and 26% in Hong Kong (Hui et al., 2006). Overall MARS total score in our study (3.68 ±2.90) is comparably lower to that of developed countries, as MARS total score had a mean of 6.0 to 7.7 in a UK sample (Fialko et al., 2008; Jaeger et al., 2012), and 5.5 for schizophrenia patients in France (Zemmour et al., 2016).Medication adherence of patients affected by recurrent schizophrenia in China was found to be relatively low. Risk factors for non-adherence to medication in recurrent schizophrenia patients include older age, unsteady income, acute period and severity of illness.

Efficacy and safety of brexpiprazole in acute management of psychiatric disorders: a meta-analysis of randomized controlled trials.

Brexpiprazole is a new atypical antipsychotic for schizophrenia management and as adjunct in major depressive disorder (MDD). We searched randomized controlled trials (RCT) to review brexpiprazole efficacy and tolerability in acute management of schizophrenia and MDD using PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials. A meta-analysis was conducted using the identified 14 RCT to assess its efficacy using positive and negative syndrome scale (PANSS), clinical global impressions - severity of illness (CGI-S), personal and social performance scale (PSP), Montgomery-Åsberg depression rating scale (MADRS), Sheehan disability scale (SDS) and Hamilton depression rating scale (HDRS17). The mean difference comparing brexpiprazole and placebo were PANSS -4.48, CGI-S -0.23 and PSP 3.24 favoring brexpiprazole. Compared to aripiprazole and quetiapine, brexpiprazole showed similar efficacy. In MDD, brexpiprazole showed efficacy compared to placebo demonstrated by MADRS -1.25, SDS -0.37 and HDRS17 -1.28. Brexpiprazole was associated with side effects including akathisia risk ratio (RR) = 1.72; weight increase RR = 2.74 and somnolence RR = 1.87. Compared to 4 mg, brexpiprazole 2 mg was associated with less risk of akathisia and somnolence. Brexpiprazole demonstrated significant improvements in schizophrenia and MDD and is well-tolerated; however, associated with akathisia and somnolence. These findings will guide psychiatrists and pharmacists in their clinical role for supporting psychiatric patients care.

Efficacy and Safety of Cariprazine in Acute Management of Psychiatric Disorders: a Meta-Analysis of Randomized Controlled Trials.

Cariprazine is a new atypical antipsychotic drug approved for the treatment of schizophrenia and bipolar disorders. we searched the published randomized controlled-trials (RCT) to review cariprazine efficacy and tolerability using the databases (PubMed, EUDRACT, ClinicalTrials.gov and Cochrane Central Register of Controlled Trials) for cariprazine role in managing the following psychiatric conditions (schizophrenia, bipolar mania, bipolar depression and major depressive disorder). A meta-analysis was conducted using the identified 13 clinical trials to assess efficacy using with the outcomes: positive and negative syndrome scale (PANSS), clinical global impressions - severity of Illness (CGI-S), young mania rating scales (YMRS), Montgomery Asberg depression rating scale (MADRS) and Hamilton rating scale for depression (HAM-D). The risk of discontinuation due to adverse effects and common side effects were examined. The mean difference in change from baseline for PANSS was -6.23 (95% Confidence Interval (CI) -7.18, -5.28) favoring cariprazine treatment (p<0.00001). Similarly, mean difference for CGI-S was -0.36 (95% CI -0.41, -0.30), YMRS -5.64 (95% CI -6.86, -4.43), MADRS -1.43 (95% CI -1.88, -0.99) and HAM-D -1.52 (95% CI -2.28, -0.76). The risk ratio (RR) of discontinuing due to adverse events was 1.18 (95% CI 1.01, 1.38) meaning risk increased by 18% in cariprazine group with RR for EPS related side effects 2.82 (95% CI 2.47, 3.22) reflecting an increased risk of experiencing EPS related side effects by 182%. Cariprazine was also associated with an increased incidence of side effects such as akathisia, nausea and insomnia. Cariprazine demonstrates significant improvements in symptom intensity control in patients suffering from psychiatric conditions including schizophrenia, bipolar disorders and depression and is considered well-tolerated with similar rates of trials discontinuation; however, cariprazine was associated with a higher risk of EPS side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting psychiatric patients care.

Efficacy and Safety of Lumateperone for Treatment of Schizophrenia

Individuals living with schizophrenia are affected by cardiometabolic, endocrine, and motor adverse effects of current antipsychotic medications. Lumateperone is a serotonin, dopamine, and glutamate modulator with the potential to treat schizophrenia with few adverse effects. To examine the efficacy and safety of lumateperone for the short-term treatment of schizophrenia. This randomized, double-blind, placebo-controlled, phase 3 clinical trial was conducted from November 13, 2014, to July 20, 2015, with data analyses performed from August 13 to September 15, 2015. Patients with schizophrenia who were aged 18 to 60 years and were experiencing an acute exacerbation of psychosis were enrolled from 12 clinical sites in the United States. Patients were randomized 1:1:1 (150 patients in each arm) to receive lumateperone tosylate, 60 mg; lumateperone tosylate, 40 mg (equivalent to 42 or 28 mg, respectively, of the active moiety lumateperone); or placebo once daily for 4 weeks. The prespecified primary efficacy end point was mean change from baseline to day 28 in the Positive and Negative Syndrome Scale (PANSS) total score vs placebo. The key secondary efficacy measure was the Clinical Global Impression-Severity of Illness (CGI-S) score. The PANSS subscale scores, social function, safety, and tolerability were also assessed. The study comprised 450 patients (mean [SD] age, 42.4 [10.2] years; 346 [77.1%] male; mean [SD] baseline PANSS score, 89.8 [10.3]; mean [SD] baseline CGI-S score, 4.8 [0.6]). In the prespecified modified intent-to-treat efficacy analysis (n = 435), 42 mg of lumateperone met the primary and key secondary efficacy objectives, demonstrating a statistically significant improvement vs placebo from baseline to day 28 on the PANSS total score (least-squares mean difference [LSMD], -4.2; 95% CI, -7.8 to -0.6; P = .02; effect size [ES], -0.3) and the CGI-S (LSMD, -0.3; 95% CI, -0.5 to -0.1; P = .003; ES, -0.4). For 28 mg of lumateperone, the LSMD from baseline to day 28 was -2.6 (95% CI, -6.2 to 1.1; P = .16; ES, -0.2) on the PANSS total score and -0.2 (95% CI, -0.5 to 0.0; P = .02; ES, -0.3) on the CGI-S. Both lumateperone doses were well tolerated without clinically significant treatment-emergent motor adverse effects or changes in cardiometabolic or endocrine factors vs placebo. Lumateperone demonstrated efficacy for improving the symptoms of schizophrenia and had a favorable safety profile. ClinicalTrials.gov identifier: NCT02282761.

Efficacy of risperidone and haloperidol in treatment of schizophrenia in tertiary care hospital

Background: Schizophrenia is a chronic debilitating disease with significant morbidity and mortality that often requires either typical or atypical antipsychotic pharmacotherapy. Atypical antipsychotic drugs are preferred over typical because of lower risk of extra pyramidal side effects. As there is paucity of data in Indian population, the present study was taken up to evaluate the efficacy of haloperidol and risperidone in the treatment of schizophrenia.Methods: It was a comparative study conducted on 60 patients of Schizophrenia for one year in a tertiary care hospital. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug risperidone and group 2 with typical antipsychotic drug Haloperidol and both groups received the treatment for one year. Efficacy was measured using positive and negative syndrome scale (PANSS), clinical global impression - severity of illness (CGI-S), clinical global impression - improvement (CGI-I) scales.Results: Both haloperidol and risperidone were associated with comparable baseline to endpoint reduction in symptom severity. However, risperidone treated subjects had significantly greater decrease in symptom severity as measured by PANSS score and total score, CGI-S scale. However, there is no significant difference between two groups in terms of CGI-S score.Conclusions: The reduction in positive, negative and general scores in risperidone treated patients were significant with that of haloperidol treated patients.

Efficacy and Safety of Brexpiprazole for the Treatment of Agitation in Alzheimer's Dementia: Two 12-Week, Randomized, Double-Blind, Placebo-Controlled Trials

ObjectiveTo assess the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer's dementia (AAD). DesignTwo 12-week, randomized, double-blind, placebo-controlled, parallel-arm studies (NCT01862640; NCT01922258). SettingStudy 1: 81 sites in 7 countries. Study 2: 62 sites in 9 countries. ParticipantsPatients with AAD (Study 1: 433 randomized; Study 2: 270 randomized) in a care facility or community-based setting. Stable Alzheimer disease medications were permitted. InterventionStudy 1 (fixed dose): brexpiprazole 2 mg/day, brexpiprazole 1 mg/day, or placebo (1:1:1) for 12 weeks. Study 2 (flexible dose): brexpiprazole 0.5–2 mg/day or placebo (1:1) for 12 weeks. MeasurementsCohen-Mansfield Agitation Inventory (CMAI) (Total score range: 29–203; higher scores indicate more frequent agitated behaviors), and Clinical Global Impression – Severity of illness (CGI-S) as related to agitation. Safety was also assessed. ResultsIn Study 1, brexpiprazole 2 mg/day demonstrated statistically significantly greater improvement in CMAI Total score from baseline to Week 12 than placebo (adjusted mean difference, −3.77; confidence limits, –7.38, –0.17; t(316) = –2.06; p = 0.040; MMRM). Brexpiprazole 1 mg/day did not show meaningful separation from placebo (0.23; −3.40, 3.86; t(314) = 0.12; p = 0.90; MMRM). In Study 2, brexpiprazole 0.5–2 mg/day did not achieve statistical superiority over placebo (–2.34; –5.49, 0.82; t(230) = −1.46; p = 0.15; MMRM). However, a benefit was observed in post hoc analyses among patients titrated to the maximum brexpiprazole dose of 2 mg/day compared with similarly titrated placebo patients (−5.06; −8.99, −1.13; t(144) = −2.54; p = 0.012; MMRM). On the CGI-S, a greater numerical improvement than placebo was demonstrated for brexpiprazole 2 mg/day in Study 1 (−0.16; −0.39, 0.06; t(337) = −1.42; nominal p = 0.16; MMRM), and a greater improvement for brexpiprazole 0.5–2 mg/day in Study 2 (−0.31; −0.55, −0.06; t(222) = −2.42; nominal p = 0.016; MMRM). In Study 1, treatment-emergent adverse events (TEAEs) with incidence ≥5% among patients receiving brexpiprazole 2 mg/day were headache (9.3% versus 8.1% with placebo), insomnia (5.7% versus 4.4%), dizziness (5.7% versus 3.0%), and urinary tract infection (5.0% versus 1.5%). In Study 2, TEAEs with incidence ≥5% among patients receiving brexpiprazole 0.5–2 mg/day were headache (7.6% versus 12.4% with placebo) and somnolence (6.1% versus 3.6%). In both studies, the majority of TEAEs were mild or moderate in severity. ConclusionsBrexpiprazole 2 mg/day has the potential to be efficacious, safe, and well tolerated in the treatment of AAD.

Effect of Yokukansan for the Treatment of Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Retrospective Analysis of Consecutive Patients.

The herbal medicine Yokukansan (YKS; Yi-Gan San in Chinese) is reported to be effective for treating rapid eye movement sleep behavior disorder (RBD). However, the effectiveness and safety of YKS treatment have not been confirmed in a large sample. Thus, we retrospectively analyzed the outcomes of YKS treatment on patients with RBD using clinical records. Treatment outcomes were evaluated using the Clinical Global Impression of Illness Severity (CGI-S) and Improvement (CGI-I) scales. Patients with scores of 1 (very much improved) and 2 (much improved) on the CGI-I were classified as responders. After excluding patients with very mild RBD symptoms and those without detailed clinical information, 36 patients with idiopathic RBD including 17 receiving YKS monotherapy and 19 receiving YKS add-on therapy in addition to other medication were analyzed. The patients' mean age [standard deviation, SD] was 69.3 [6.8] years, and the mean duration of RBD morbidity [SD] was 5.7 [3.5] years at the start of YKS treatment. Importantly, 12 of 17 patients (70.6%) receiving YKS monotherapy were responders. However, among patients receiving YKS add-on therapy, the proportion of responders was substantially lower (4 of 19 patients; 21.1%). No adverse events were reported, other than mild gastric distress in one case. Considering the effectiveness of YKS and the low likelihood of adverse events, YKS should be considered as a potential treatment for patients with RBD. Matsui K, Sasai-Sakuma T, Ishigooka J, Nishimura K, Inoue Y. Effect of yokukansan for the treatment of idiopathic rapid eye movement sleep behavior disorder: a retrospective analysis of consecutive patients. J Clin Sleep Med. 2019;15(8):1173-1178.

Evaluation of serum inflammatory markers in treatment-resistant manic patients and adequate responder manic patients

Mania is accompanied with immune activation as indicated by increased pro-inflammatory cytokines, acute phase proteins; and carcinoembryonic antigen (CEA) is known to accompany signs of immune-inflammatory responses in bipolar disorder (BD) and medical disorders. In this study, it was aimed to compare high sensitivity C-reactive protein (hsCRP), CEA levels and white blood cells (WBCs) counts in the treatment-resistant BD (Group 3), the treatment-responsive BD patients (Group 2), and the healthy control group (Group 1). The sociodemographic data form, the Young Mania Rating Scale (YMRS), the Hamilton Depression Rating Scale (HDRS), and the Clinical Global Impression Severity of Illness (CGI-S) Scale were applied to the patients. In Group 3, the WBCs counts, and CEA levels were significantly higher than the other two groups. There was a positive correlation between WBCs counts and YMRS and CGI-S scores in all manic patients. There was a positive correlation between CEA levels and YMRS, HDRS and CGI-S in manic patients. This study shows that there is an activation of the immune-inflammatory response system in treatment resistant manic patients; and, WBCs counts and CEA levels are associated with severity of disease in manic patients.

Adjunctive brexpiprazole for elderly patients with major depressive disorder: An open-label, long-term safety and tolerability study.

ObjectivesThe objective of this study was to evaluate the long‐term safety and tolerability of flexible‐dose brexpiprazole adjunct to antidepressant treatment (ADT) in elderly patients with major depressive disorder (MDD).MethodsElderly patients (≥65 years) with MDD and inadequate response to ≥1 ADT during the current episode were recruited to a 26‐week, interventional, open‐label study (NCT02400346) at outpatient centers in the USA and Europe. All patients received brexpiprazole 1 to 3 mg/day adjunct to their current ADT. Safety outcomes included adverse events (AEs), movement disorder scales, and standard safety assessments (vital signs, laboratory safety parameters, physical examination, electrocardiograms). Exploratory efficacy outcomes included the Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impressions‐Severity of Illness (CGI‐S), and Social Adaptation Self‐Evaluation Scale (SASS).ResultsOf the 132 treated patients, 88 (66.7%) completed the study and 44 (33.3%) withdrew, including 24 who withdrew because of AEs (18.2%). Overall, 102 patients (77.3%) experienced ≥1 treatment‐emergent AE (TEAE), which were mostly mild or moderate in severity. Treatment‐emergent AEs with the highest incidence were fatigue (15.2%) and restlessness (12.9%). The most common TEAE leading to withdrawal was fatigue (3.0%). No consistent clinically relevant findings were seen with regard to movement disorder scales or standard safety assessments. Mean (standard error) efficacy score changes from baseline to week 26 were: MADRS total, −14.5 (0.9); CGI‐S, −1.8 (0.1); and SASS, 3.2 (0.5).ConclusionsLong‐term (26‐week) treatment with adjunctive brexpiprazole was generally well tolerated in elderly patients with MDD and inadequate response to prior ADT. Improvements were observed in depressive symptoms and social functioning.

Efficacy of Tianeptine 25-50 mg in Elderly Patients With Recurrent Major Depressive Disorder: An 8-Week Placebo- and Escitalopram-Controlled Study.

The present placebo-controlled study evaluated the efficacy and safety of 8 weeks of treatment with tianeptine 25-50 mg/d in elderly patients suffering from major depressive disorder (MDD) according to DSM-IV-TR. Escitalopram 5-10 mg/d was used as an active comparator. Elderly outpatients aged at least 65 years with a primary diagnosis of moderate to severe episode of recurrent MDD were recruited by psychiatrists in 44 clinical centers in 10 countries from October 2013 to January 2016. Patients were randomly assigned to receive tianeptine (n = 105), placebo (n = 107), or escitalopram (n = 99) for 8 weeks. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇) total score. Tianeptine improved depressive symptoms, as evaluated by the HDRS₁₇ total score in terms of absolute change from baseline (week 0) to week 8 (placebo-tianeptine difference [SE] of 3.84 [0.85] points, P < .001, using a last-observation-carried-forward approach) and response to treatment (tianeptine: 46.7%; placebo: 34.0%, estimate [SE] = 12.70% [6.70], P = .06). A sensitivity analysis using a mixed model for repeated measures confirmed the main results on HDRS total s​core. The placebo-tianeptine difference (SE) was 0.66 (0.15) for Clinical Global Impressions-Severity of Illness (95% CI, 0.37 to 0.96; P < .001) and 0.57 (0.14) for Clinical Global Impressions- Improvement (95% CI, 0.30 to 0.83; P < .001). Positive results were also obtained with the active control escitalopram (HDRS₁₇ total score placebo-escitalopram difference of 4.09 ± 0.86 points, P < .001), therefore validating the sensitivity of the studied population. Tianeptine was well tolerated, with only minimal differences in tolerability from placebo. The present study provides robust evidence that an 8-week treatment period with tianeptine 25-50 mg is efficacious and well tolerated in depressed patients aged 65 years or older. EudraCT identifier: 2012-005612-26​.

Efficacy and tolerability of fluvoxamine in adults with social anxiety disorder: A meta-analysis.

No meta-analysis for estimating the comprehensive efficacy and tolerability of fluvoxamine in patients with social anxiety disorder (SAD) has been published. To investigate the efficacy and tolerability of fluvoxamine in adults with SAD, trials meeting the following criteria were identified: population: ≥18 years of age with a diagnosis of SAD; intervention: fluvoxamine; study design: placebo-controlled randomized controlled trials (RCTs); outcomes: efficacy and tolerability outcomes. We conducted a comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for RCTs on January 3, 2018. Review Manager 5.3 and Stata Version 12.0 software were used for all statistical analyses. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous variables, and odds ratios (ORs) with 95% CIs were calculated for dichotomous variables. Cochrane Collaboration's risk of bias tool was used to assess the likelihood of risk of bias. Efficacy was assessed by mean changes in the Liebowitz Social Anxiety scale (LSAS) total score and the Clinical Global Impression Severity of Illness (CGI-S) score as well as the response rate. Tolerability was mainly assessed by the discontinuation rate due to adverse events (AEs) and the incidence of most frequent treatment-emergent AEs (TEAEs). This meta-analysis included 5 RCTs. Mean changes in LSAS total and CGI-S scores were both significantly greater in patients treated with fluvoxamine than those treated with placebo (LSAS: MD = 11.90, 95% CI = 8.09-15.71, P < .001; CGI-S: MD = 0.52, 95% CI = 0.33-0.72, P < .001). Response rate was higher in fluvoxamine group as compared with placebo (OR = 1.71, 95% CI = 1.30-2.24, P < .001). Additionally, mean change in the Sheehan disability scale score was significantly greater in fluvoxamine group than placebo group (OR = 2.11, 95% CI = 1.03-3.18, P < .001). The discontinuation rate due to AEs was higher in patients that received fluvoxamine compared to those received placebo (OR = 5.99, 95% CI = 2.24-15.99, P < .001), as was the incidence of overall TEAEs (any AE) (OR = 2.66, 95% CI = 1.77-4.02, P < .001). However, the incidence of serious AEs was not significantly different between the 2 groups (OR = 0.99, 95% CI = 0.25-3.89, P = .99). Fluvoxamine was found to be effective in adult patients with SAD, with acceptable tolerability.

O7.5. LONG-TERM SAFETY AND TOLERABILITY OF BREXPIPRAZOLE IN PATIENTS WITH SCHIZOPHRENIA

BackgroundLong-term maintenance treatment is recommended to control the symptoms of schizophrenia1,2; therefore, safety monitoring for longer than the period required to treat an acute exacerbation is warranted. The aim of the present study (Lighthouse extension; NCT01810783) was to assess the long-term safety and tolerability of open-label treatment with brexpiprazole (flexible dose 1–4 mg/day) in adult patients with schizophrenia. Brexpiprazole is a serotonin-dopamine activity modulator that acts as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors, and as an antagonist at the 5-HT2A and noradrenaline α1B/2C receptors, all with subnanomolar potency. Brexpiprazole is approved in the US as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD) and in the US, Australia and Canada as monotherapy for treatment of schizophrenia.MethodsPatients rolled over into this 52-week open-label study from a randomized, double-blind, placebo-controlled, active referenced, Phase 3 study (Lighthouse3; NCT01810380). The primary endpoint was safety and tolerability. Efficacy was assessed as an exploratory endpoint using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions – Severity of illness (CGI-S) and Improvement (CGI-I) scales, and the Personal and Social Performance (PSP) scale. Changes from baseline were analyzed using a mixed model repeated measurements (MMRM) approach.Results210 patients were enrolled, and 101 (48.3%) completed the study. The mean and mean modal doses of brexpiprazole were 3.07mg/day and 3.18mg/day, respectively; at last visit, 50% of the patients received 4mg/day. Among patients who took ≥1 dose of brexpiprazole, the incidence of discontinuation due to treatment-emergent adverse events (TEAEs) was 17.2%. TEAEs with an incidence of ≥5.0% were schizophrenia (worsening of the underlying disease; 11.5%), weight increase (10.5%), headache (8.6%), and insomnia (8.1%). Most TEAEs were mild or moderate in severity. The mean increase in body weight from baseline to Week 52 was 2.6kg (observed cases [OC]) and 19.6% of patients had a weight increase ≥7% at any time during the study. There were no clinically relevant findings for either metabolic parameters (lipids and glucose), or for events related to ECGs, vital signs, extrapyramidal symptoms, or prolactin. Patients’ symptoms and functioning showed continual improvement; at Week 52, mean change from baseline in PANSS was -6.8 (95% confidence interval [CI]: -9.3, -4.2); CGI-S: -0.4 (95%CI: -0.5, -0.2); and PSP: 4.2 (95%CI: 2.2, 6.1). The CGI-I score at Week 52 was 2.8 (95%CI: 2.6, 3.1). The percentage of responders (reduction of ≥30% from baseline in PANSS total score or a CGI-I score of 1 [very much improved] or 2 [much improved]) increased throughout the study, from 16% (OC and last observation carried forward [LOCF]) at Week 1 to 48% (OC) and 35% (LOCF) at Week 52.DiscussionTreatment with open-label brexpiprazole 1–4 mg/day was generally well tolerated for up to 52 weeks in patients with schizophrenia. Further, long-term treatment with brexpiprazole was associated with continued improvement in efficacy measures and functional outcomes.

A Subgroup Analysis of the Impact of Vortioxetine on Functional Capacity, as Measured by UPSA, in Patients with Major Depressive Disorder and Subjective Cognitive Dysfunction.

BackgroundWe evaluated vortioxetine’s effects on functional capacity in demographic and clinical subgroups of patients with major depressive disorder.MethodsThis was an exploratory analysis of the CONNECT study (NCT01564862) that evaluated changes in functional capacity using University of California San Diego Performance-based Skills Assessment data, categorized by sex, age, education, employment status, and baseline disease severity (Montgomery-Åsberg Depression Rating Scale, Clinical Global Impressions–Severity of Illness).ResultsGreater changes in University of California San Diego Performance-based Skills Assessment composite scores were observed with vortioxetine vs placebo in specific subgroups: males (∆+3.2), females (∆+2.9), 45–54 or ≥55 years (∆+5.6, ∆+3.4), working (∆+2.8), high school or greater education (∆+2.7, ∆+2.8), disease severity (Montgomery-Åsberg Depression Rating Scale, <30, ∆+3.5; ≥30, ∆+2.5; Clinical Global Impressions–Severity of Illness ≤4, ∆+2.8; >4, ∆+3.0), major depressive episodes (≤2, >2 [∆+2.7,+3.3]), and episode duration (≤22, >22 weeks [∆+3.7,+2.4]).ConclusionsOur findings support the need for additional studies to assess whether vortioxetine improves functional capacity within specific patient subgroups.Clinical Trial Registryclinicaltrials.gov: NCT01564862

Observation and analysis of clinical efficacy of melatonin on AOPP-induced delirium patients.

To observe the clinical efficacy of melatonin on acute organophosphorus pesticide poisoning (AOPP). In this randomized control trial, a total of 59 AOPP patients with subsequent delirium were randomly divided into two groups, the melatonin group (n=29) and the placebo-controlled group (n=30). Patients in the melatonin group (n=29) underwent oral administration of melatonin in addition to the symptomatic treatment, while those in the placebo-controlled group took a placebo in addition to the symptomatic treatment. Before and 12 weeks after treatment, adverse events of participants in both groups were classified according to their scores in the assessment of the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-Severity of Illness (CGI-SI) scale, and Treatment Emergent Symptom Scale (TESS). The excellence rates of patients in the melatonin group and the placebo-controlled group were 82.75% and 30.00%, respectively (χ2 = 17.054, p < 0 .01). No adverse events were identified in all participants. Melatonin may serve as an effective drug in the treatment of AOPP-induced deliration.

The effect of the severity of nicotine dependence on psychopathology, insight and illness severity in schizophrenia patients

Aim: Compared to the general healthy population, the prevalence of smoking is found to be much higher among people with schizophrenia. Our study aims to determine the prevalence of nicotine dependence and investigate the effects of the severity of nicotine dependence on psychopathology, illness severity and insight in a population of people with schizophrenia. Material and Methods: A cross-sectional study was carried out in a psychotic disorders outpatient clinic at Bakirkoy Training and Research Hospital. Four hundred and ten schizophrenia patients were administered by the Positive and Negative Symptom Scale (PANNS), Schedule for Assessment of Insight, Clinical Global Impression Severity of Illness (CGI-S) and the Turkish version of Fagerstrom Test for Nicotine Dependence (FTND). Results: The prevalence of nicotine dependence among the patients was 47.3%. The one-way analysis of variance revealed that subjects with severe nicotine dependence scored more in the positive subscale of PANNS and CGI-S compared with patients with mild-moderate nicotine dependence. Those with severe nicotine dependence were also prescribed higher doses of antipsychotic. Conclusions: Our findings indicate an association between nicotine dependence, positive symptoms and severity of illness. Identifying this relationship can be helpful in the management of smoking cessation treatment in patients with schizophrenia.

Associations of plasma leptin to clinical manifestations in reproductive aged female patients with panic disorder

Preclinical studies suggest the implication of the adipocyte hormone leptin in anxiety and fear processes. We explored for potential differences regarding plasma leptin, cortisol and the ratio leptin/Body Mass Index (BMI) between 27 medication-free female patients with Panic Disorder (PD) and 42 age-matched female controls, and for potential associations between plasma leptin and psychometric evaluations including number of panic attacks during last week, Clinical Global Impression-Severity of Illness (CGI-S) and Symptoms Checklist-90-Revised (SCL-90-R). Cortisol levels showed no differences between patients and controls, or correlations to leptin or to any clinical features. Both groups demonstrated a strong positive correlation between leptin and BMI and similar leptin and leptin/BMI, despite patients’ lower BMI. However, patients –but not controls- demonstrated significant negative correlations of leptin to the ‘somatization’, ‘anxiety’, and ‘phobic anxiety’ SCL-90-R subscales. Moreover, there was a significant negative correlation of leptin and of leptin/BMI ratio to the number of panic attacks during last week, while higher CGI-S was associated with lower leptin/BMI ratio. Our results, limited to PD female patients, suggest that lower leptin serum levels are significantly associated with greater severity of psychopathological manifestations, including number of panic attacks, symptoms of somatization, anxiety and phobic anxiety and overall clinical presentation.

Glutamatergic Agents as Add-On Medication for the Treatment of Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

The aim of the present study was to review the existing literature on clinical trials with glutamatergic agents in adults with obsessive-compulsive disorder (OCD) and to perform a meta-analysis to estimate the overall effect size. We searched in MEDLINE, Embase, and the Cochrane Library for eligible studies, using the following search terms: (glutamate OR glutaminergic OR glutamatergic OR NMDA OR AMPA OR kainate) AND (obsessive-compulsive disorder OR obsessive OR compulsive OR OCD). A separate search was performed for generally known glutamatergic agents. The databases were searched for articles published by May 31, 2015. Eligible studies were double-blind, randomized controlled trials that tested the efficacy of add-on treatment with a glutamatergic agent in patients with OCD. Data were extracted independently by 2 reviewers. We extracted dichotomous data (number of patients with response and remission) to estimate relative risk ratios (RRs), as well as continuous data (scores in Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity of Illness and -Improvement scales), which were used to estimate standardized mean differences. Effect sizes were estimated using a random-effects model. Eight randomized controlled trials were identified. The overall ratio for response was RR = 3.71 (95% CI, 2.35-5.83; P < .001). When limited to the studies with treatment-resistant patients, the effect size remained significant (RR = 4.30; 95% CI, 2.19-8.43; P < .001). Secondary outcomes, such as the standardized mean differences for continuous data, showed the statistically significant superiority (P < .001) of glutamatergic agents over placebo. The risk of dropouts was RR = 1.18 (95% CI, 0.83-1.69; P = .361) and the risk of dropouts due to adverse effects was RR = 3.04 (95% CI, 1.57-5.89; P = .001). Glutamatergic agents are effective as add-on treatment for OCD in general and especially for treatment-refractory OCD.

The Effectiveness of Telepsychiatry-Based Culturally Sensitive Collaborative Treatment for Depressed Chinese American Immigrants

This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants. Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM-IV major depressive disorder (MDD) identified by the Mini-International Neuropsychiatric Interview. Eligible patients were randomized to receive either T-CSCT or treatment as usual (TAU) for 6 months. T-CSCT involves (1) cultural consultation via videoconference and (2) care management. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS₁₇); positive response was defined as a ≥ 50% decrease in HDRS₁₇ score, and remission was defined as HDRS₁₇ score ≤ 7. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Outcomes were compared using multivariate logistic regression and mixed-model for repeated measures methods. Among participants (N = 190), 63% were female, and the mean (SD) age was 50 (14.5) years. They were randomized to T-CSCT (n = 97; 51%) or TAU (n = 93; 49%). Using multivariate logistic regression analyses, the odds of achieving response and remission were significantly greater for the T-CSCT group compared to the control group (odds ratio [OR] = 3.9 [95% CI, 1.9 to 7.8] and 4.4 [95% CI, 1.9 to 9.9], respectively). Multivariate general linear model analyses showed that patients in the T-CSCT group had significantly greater improvement over time in HDRS₁₇ (F4,95 = 4.59, P = .002), CGI-S (F4,95 = 4.22, P = .003), and CGI-I (F4,95 = 2.95, P = .02) scores. T-CSCT is effective in improving treatment outcomes of Chinese immigrants with MDD. ClincialTrials.gov identifier: NCT00854542.

Effectiveness of blonanserin for patients with drug treatment-resistant schizophrenia and dopamine supersensitivity: A retrospective analysis.

Dopamine supersensitivity psychosis (DSP) is one of the key factors contributing to the development of antipsychotic treatment-resistant schizophrenia (TRS). We investigated the efficacy of blonanserin, an atypical antipsychotic, for patients with TRS and DSP. In this 12-month retrospective follow-up study, we investigated the cases of eight consecutive patients with unstable TRS and DSP treated with blonanserin as an add-on therapy. We examined changes in scores for the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression-Severity of Illness (CGI-S) scale and the Global Assessment of Functioning scale (GAF) during the 12 months after the administration of blonanserin. The patients' total scores on the BPRS and GAF scores were significantly improved by 3 months at the latest. Positive BPRS and CGI-S scores were also improved by 6 months at the latest. The total chlorpromazine-equivalent doses of antipsychotics were significantly reduced from 1462.3±499.6mg to 794.1±642.8mg (p=0.001) after 12 months of blonanserin treatment, with a favorable safety and tolerability profile. Blonanserin may be a promising antipsychotic for the treatment of TRS and DSP.