Clinical Global Impressions-Severity Of Illness Scores Research Articles

Decrease in Social Zeitgebers Is Associated With Worsened Delayed Sleep-Wake Phase Disorder: Findings During the Pandemic in Japan.

BackgroundDelay in sleep-wake rhythms was observed in the general population during the coronavirus disease 2019 (COVID-19) pandemic. Patients with delayed sleep-wake phase disorder (DSWPD) may have also experienced exacerbation of symptoms, but no studies have investigated this topic. In this study, we aimed to retrospectively examine the changes in symptoms of outpatients with DSWPD both before and during the pandemic and to identify the factors associated with the exacerbation of sleep-wake rhythms.MethodsWe included outpatients with DSWPD aged 16 years or older who visited the outpatient clinic due to sleep disorders between January and September 2020. Decreased social zeitgebers was defined as a reduction of 50% or more in the frequency of commuting to school or work during the COVID-19 pandemic. The severity of DSWPD was assessed using the clinical global impressions - severity of illness (CGI-S) at two points: before and during the pandemic. We defined the worsened, unchanged, and improved groups as those whose CGI-S scores worsened by at least one point, remained unchanged, and improved by at least one point, respectively. Multivariate logistic regression analysis was performed to determine the factors associated with worsened DSWPD symptoms.ResultsSixty patients with DSWPD were eligible for this study. Even before the pandemic, patients who were unemployed or did not attend school tended to show more severe DSWPD symptoms. During the pandemic, 27 patients belonged to the worsened group; 28 patients, unchanged group; and 5 patients, improved group. Decreased social zeitgebers (odds ratio [OR] = 6.668, 95% confidence interval [CI]: 1.653–26.891, p < 0.05) and comorbid mood disorders (OR = 8.876, 95% CI: 1.714–45.974, p < 0.05) showed independent significant associations with the worsening of DSWPD symptoms.ConclusionsDuring the pandemic, the symptoms of DSWPD tended to worsen. The obtained findings emphasize the importance of social zeitgebers, suggesting the need for external motivation in DSWPD treatment.

Transcutaneous electrical acupoint stimulation for children with attention-deficit/hyperactivity disorder: a randomized clinical trial

Little is known about the effects of transcutaneous electrical acupoint stimulation (TEAS) for children with attention-deficit/hyperactivity disorder (ADHD). Here, we carried out a 4 week randomized clinical trial in which patients aged 6–12 years old with an ADHD diagnosis received TEAS or sham TEAS. The primary outcome measure was the investigator-rated Clinical Global Impression-Improvement (CGI-I) score at week 4. Secondary outcomes included changes from baseline to week 4 in the investigator-rated Clinical Global Impression-Severity of Illness (CGI-S) score, the Conners’ Parent/Teacher Rating Scales-Revised: Short Form (CPRS-R: S/CTRS-R: S) score, go/no-go task performance, and functional near-infrared spectroscopy (fNIRS)-based oxygenated hemoglobin level within the prefrontal cortex. At week 4, the CGI-I score indicated improvement in 33.3% of the TEAS group compared with 7.7% of the sham group (P = 0.005). The TEAS group had a greater decrease in the mean CGI-S score (−0.87) than the sham TEAS group (−0.28) (P = 0.003). A greater enhancement in the mean cerebral oxygenated hemoglobin within the prefrontal cortex was found in the TEAS group (0.099 mM mm) compared with the sham TEAS group (0.005 mM mm) (P < 0.001). CPRS-R: S score, CTRS-R: S score, and go/no-go performance exhibited no significant improvement after TEAS treatment. The manipulation-associated adverse events were uncommon in both groups, and events were very mild. Our results show that noninvasive TEAS significantly improved general symptoms and increased prefrontal cortex blood flow within 4 weeks for children with ADHD. Further clinical trials are required to understand the long-term efficacy in a larger clinical sample. This trial was registered on ClinicalTrials.gov (NCT 03917953).

Agomelatine in Standard Medical Practice in Depressed Patients: Results of a 1-Year Multicentre Observational Study In France.

Background and ObjectivesNon-interventional studies are a valuable source of evidence that is complementary to traditional randomised, blinded and controlled clinical trials, for evaluating antidepressants in a real-world setting. The aim of the present study was to document the use of agomelatine in current medical practice and evaluate its effectiveness and safety in outpatients prescribed agomelatine to treat their current depressive episode.MethodsThis 12-month observational French study included patients initiating agomelatine treatment. The intensity and severity of depression were assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17) total score and the Clinical Global Impression-Severity of Illness (CGI-S) scale. Patients’ quality of life and functioning were measured using the Quality of Life in Depression Scale and the Sheehan Disability Scale, respectively. The safety measures included emergent adverse events and biological samplings, with a focus on liver acceptability.ResultsA total of 1484 patients (70% of women; 49.6 ± 15.4 years of age) were enrolled in the study. Most patients (62.3%) were treated with agomelatine for at least 6 months and 28.8% were treated for at least 1 year. Mean HAM-D17 total score and mean CGI-S scores decreased by 13.6 ± 8.1 and 2.1 ± 1.5 points, respectively, from baseline to last visit on agomelatine. Rates of responders (i.e. with a decrease in HAM-D17 total score by at least 50%) and remitters (HAM-D total score < 7) at the last visit were 90.7% and 56.0%, respectively. The mean HAM-D total score decreased after agomelatine withdrawal (− 4.1 ± 6.7) until the last visit. The quality of life and daily functioning of patients improved, while the numbers of days lost and underproductive days decreased over the follow-up period. Safety findings were in accordance with the known information regarding agomelatine.ConclusionIn the current medical practice, this study confirms the effectiveness and good tolerability of agomelatine administered for a treatment period in agreement with guideline recommendations.Trial registration numberISRCTN53570733 on 27 August 2010.

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 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.

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.

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.

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.

An exploratory cross-sectional study on the impact of education on perception of stigma by Chinese patients with schizophrenia.

BackgroundStigma is a major issue across various society and cultures, and few studies focus on the perception of stigma by Chinese patients with schizophrenia. In the current cross-sectional study, we sought to assess the extent of internalized stigma among outpatients with schizophrenia in China and to investigate whether education level correlated with the experience of stigma.MethodsOutpatients with schizophrenia were evaluated using the brief psychosis rating scale (BPRS), the positive and negative syndrome scale (PANSS), the clinical global impression-severity of illness (CGI-SI) scale and the Stigma Scale for Mental Illness (SSMI 2C). Patients were categorized into the high education and low education group according to their educational levels.ResultsOne hundred thirty-three subjects were included in the study. Their mean course of illness was 4.32 ± 6.14 years (range, 1 month to 15 years). Their mean BPRS score was 19.87 ± 5.46, their mean PANSS score was 44.11 ± 13.1, and their mean CGI-SI score was 2.22 ± 0.81. In addition, the mean SSMI 2C score of the high education group (7.15 ± 0.98) was markedly higher than that of the low education group (5.75 ± 0.79, P < 0.05). The mean domain I score of the high education group (2.30 ± 0.76) was comparable to that of the low education group (2.07 ± 0.78, P > 0.05). The mean domain II score of the high education group (2.42 ± 0.96) was markedly higher than that of the low education group (2.01 ± 0.79, P < 0.05). Moreover, the mean domain III score of the high education group (2.43 ± 0.79) was significantly higher than that of the low education group (1.67 ± 0.77, P < 0.05).ConclusionsEducation level impacts on the perception of stigma by patients with schizophrenia and more psycho-education should be done to improve patients’ knowledge about schizophrenia.

A Randomized, Placebo-Controlled Trial of Guanfacine Extended Release in Adolescents With Attention-Deficit/Hyperactivity Disorder

Despite the continuity of attention-deficit/hyperactivity disorder (ADHD) into adolescence, little is known regarding use of nonstimulants to treat ADHD in adolescents. This phase 3 trial evaluated the safety and efficacy of guanfacine extended release (GXR) in adolescents with ADHD. This 13-week, multicenter, randomized, double-blind, placebo-controlled trial evaluated once-daily GXR (1-7 mg per day) in adolescents with ADHD aged 13 to 17 years. The primary endpoint was the change from baseline in the ADHD Rating Scale-IV (ADHD-RS-IV) total score; key secondary endpoints included scores from the Clinical Global Impressions-Severity of Illness (CGI-S), and Learning and School domain and Family domain scores from the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at week 13. A total of 314 participants were randomized (GXR, n = 157; placebo, n = 157). The majority of participants received optimal doses of 3, 4, 5, or 6 mg (30 [22.9%], 26 [19.8%], 27 [20.6%], or 24 [18.3%] participants, respectively), with 46.5% of participants receiving an optimal dose above the currently approved maximum dose limit of 4 mg. Participants receiving GXR showed improvement in ADHD-RS-IV total score compared with placebo (least-squares mean score change, -24.55 [GXR] versus -18.53 [placebo]; effect size, 0.52; p <.001). More participants on GXR also showed significant improvement in CGI-S scores compared with placebo (50.6% versus 36.1%; p = .010). There was no statistically significant difference between treatments at week 13 in the 2 WFIRS-P domains. Most treatment-emergent adverse events were mild to moderate, with sedation-related events reported most commonly. GXR was associated with statistically significant improvements in ADHD symptoms in adolescents. GXR was well tolerated, with no new safety signals reported. Dose-Optimization in Adolescents Aged 13-17 Diagnosed With Attention-Deficit/Hyperactivity Disorder (ADHD) Using Extended-Release Guanfacine HCl; http://ClinicalTrials.gov/; NCT01081132.

Safety and effectiveness of controlled-release paroxetine in routine clinical practice: results of a postmarketing surveillance study of patients with depression.

ObjectiveSelective serotonin reuptake inhibitors are commonly used in the pharmacotherapy of depression. However, adverse events can lead to their early discontinuation. This study evaluated the safety and effectiveness of paroxetine controlled-release (CR) tablets in Japanese patients with depression/depressive state (hereafter referred to as depression) in routine clinical practice in Japan.Patients and methodsThis was an open-label, noninterventional, prospective, postmarketing surveillance study. A total of 3,213 patients aged 12–92 years with depression were prescribed paroxetine CR for 8 weeks at the physician’s discretion. Safety was evaluated on the basis of the reporting of adverse drug reactions. Effectiveness was evaluated on the basis of the physician’s assessment using the Clinical Global Impression-Global Improvement (CGI-GI) and the Clinical Global Impression-Severity of Illness (CGI-SI) scales, as well as on the basis of the patients’ self-reported satisfaction. The primary effectiveness outcome was the improvement rate based on the physician’s assessment using the CGI-GI.ResultsThe incidence of adverse drug reactions was 11.2% (359/3,213; 95% confidence interval [CI]: 10.1%–12.3%). The common adverse drug reactions that accounted for 1.0% or more of the incidence were nausea (3.5%) and somnolence (2.7%). The proportion of patients who continued paroxetine CR at week 8 was 80.2% (2,577/3,213; 95% CI: 78.8%–81.6%). The improvement rate at week 8 (last observation carried forward) was 72.8% (2,132/2,927; 95% CI: 71.2%–74.4%). The proportion of patients with CGI-SI scores of moderately or severely ill decreased from 63.6% at baseline to 17.9% at week 8. The proportion of patients who were satisfied with paroxetine CR treatment was 69.8% (2,040/2,921; 95% CI: 68.1%–71.5%).ConclusionThe results of this study suggest that paroxetine CR is a well-tolerated and efficacious treatment for depression in routine clinical practice.

Efficacy and safety of aripiprazole in Chinese Han schizophrenia subjects: A randomized, double-blind, active parallel-controlled, multicenter clinical trial

ObjectiveAntipsychotics, such as aripiprazole and risperidone, are often used to treat individuals with schizophrenia. The efficacy as well as safety of aripiprazole in Western populations has been described. The objective of this study is to investigate the efficacy, safety, and tolerability of aripiprazole and risperidone in Chinese Han schizophrenia subjects in mainland China. MethodThe 6-week, double-blind, randomized, parallel study was conducted in 5 medical centers in mainland China from November 2007 to March 2011. A total of 279 subjects with a primary DSM-IV diagnosis of schizophrenia were randomly assigned (with a randomization ratio of 1:1) to aripiprazole (n=139) or risperidone (n=140). Efficacy measurements included the Positive and Negative Syndrome Scale (PANSS) total, positive, negative and general psychopathology subscale scores, and Clinical Global Impressions-Severity of Illness (CGI-S), and Improvement scale scores. Extrapyramidal symptoms (EPS), weight gain, serum prolactin level, QTc interval, and self-reported adverse events were also assessed as measures of safety and tolerability. ResultsBoth the aripiprazole and risperidone groups showed statistically significant improvement of PANSS total, positive, negative, general psychopathology subscale scores, and CGI-S scores from baseline to the endpoint (all p<0.01). Significant improvement was noted in the first week for both treatment groups. There were no significant differences in efficacy measurements between the two treatment groups. Mean change of PANSS total scores from baseline to the endpoint was −26.8±18.1 for aripiprazole and −30.0±17.7 for risperidone, (p=0.1475). The responder rate was 71% (n=99) and 76% (n=107) for aripiprazole and risperidone, respectively, (p=0.323). The incidences of EPS were similar in the aripiprazole (25%, n=35) and risperidone groups (24%, n=34), respectively (p=0.757). No clinically meaningful effects on QTc interval, QRS duration, or PR interval were observed in either treatment groups. However, the incidence of clinically significant weight gain (p=0.0118) and hyperprolactinemia (p<0.001) in the aripiprazole group was significantly lower than in the risperidone group. ConclusionThe study demonstrated that aripiprazole, as well as risperidone, had rapid and persistent efficacy for psychotic symptoms from the first week of therapy. There may be poor efficacy for aripiprazole compared with risperidone for overall improvement, but there were no significant differences in this study. Aripiprazole showed good tolerability with less weight gain and hyperprolactinemia compared with risperidone. The overall efficacy and safety of aripiprazole in Chinese Han schizophrenia subjects were similar to that reported in Western populations.

A prospective comparative study of risperidone long-acting injectable for treatment-resistant schizophrenia with dopamine supersensitivity psychosis

ObjectiveDopamine supersensitivity psychosis (DSP) is considered to be one cause of treatment-resistant schizophrenia (TRS). The authors investigated the efficacy of risperidone long-acting injections (RLAI) in patients with TRS and DSP. MethodThis is a multicenter, prospective, 12-month follow-up, observational study that included unstable and severe TRS patients with and without DSP. 115 patients with TRS were recruited and divided into two groups according to the presence or absence of DSP which was judged on the basis of the clinical courses and neurological examinations. RLAI was administered adjunctively once every 2weeks along with oral antipsychotics. We observed changes in scores for the Brief Psychiatric Rating Scales (BPRS), Clinical Global Impression—Severity of Illness (CGI-S), Global Assessment of Functioning Scale (GAF), and Extrapyramidal Symptom Rating Scale (ESRS) during the study. Of the assessed 94 patients, 61 and 33 were categorized into the DSP and NonDSP groups, respectively. ResultsWhile baseline BPRS total scores, CGI-S scores and GAF scores did not differ, the ESRS score was significantly higher in the DSP group compared with the NonDSP group. Treatment significantly reduced BPRS total scores and CGI-S scores, and increased GAF scores in both groups, but the magnitudes of change were significantly greater in the DSP group relative to the NonDSP group. ESRS scores were also reduced in the DSP group. Responder rates (≥20% reduction in BPRS total score) were 62.3% in the DSP group and 21.2% in the NonDSP group. ConclusionsIt is suggested that DSP contributes to the etiology of TRS. Atypical antipsychotic drugs in long-acting forms, such as RLAI, can provide beneficial effects for patients with DSP.Clinical trials registration: UMIN (UMIN000008487).

A cross-sectional study on perception of stigma by Chinese schizophrenia patients.

ObjectiveIn this cross-sectional study, we sought to assess the extent of internalized stigma among inpatients and outpatients with schizophrenia in the People’s Republic of China and to investigate whether education level correlated with the experience of stigma.MethodsSchizophrenia patients were evaluated using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity of Illness (CGI-S) scale and the Stigma Scale for Mental Illness (SSMI-C). Patients were categorized into high education and low education groups, according to their educational levels.ResultsOne hundred thirty-three subjects were included in the study. Their mean course of illness was 4.32±6.14 years (range: 1 month to 15 years). Their mean BPRS score was 19.87±5.46, their mean PANSS score was 44.11±13.1, and their mean CGI-S score was 2.22±0.81. In addition, their mean SSMI-C score was 6.49±0.9. The mean SSMI-C score of patients who have received high school education or above was 7.15±0.98, which was markedly higher than that of patients who have received middle school education or below, which was 5.75±0.79 (P<0.05). Before the study most patients (92.5%, 123/133) took atypical drugs.ConclusionEducation level impacts on the perception of stigma by schizophrenia patients, and more psychoeducation should be undertaken to improve patients’ knowledge about schizophrenia.

Effects of milnacipran on neurocognition, pain, and fatigue in fibromyalgia: a 13-week, randomized, placebo-controlled, crossover trial.

To investigate whether milnacipran is safe and effective in improving cognitive function in patients with fibromyalgia. Patients were randomly assigned to receive milnacipran or placebo for 6 weeks, followed by a 1-week washout and then crossover to the other arm for another 6 weeks. The overall trial lasted 13 weeks and was conducted between July 2011 and May 2013. Assessments were performed at each visit. Neurocognition was measured by the Brief Assessment of Cognition (BAC) and MATRICS. Pain was assessed by the visual analog scale (VAS) for pain. Global assessment of fibromyalgia symptoms was measured by the Fibromyalgia Impact Questionnaire (FIQ) and tender point examination. Depression was assessed by the Beck Depression Inventory (BDI). Fatigue was assessed by the Fatigue Severity Scale. Functional outcome was evaluated by the Health Assessment Questionnaire. The Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Patients Clinical Global Impression of Change were used to measure the global impression of severity and improvement. 26 subjects were screened, and 20 subjects completed the trial. The change in verbal memory (P = .001) and the composite T score (P = .044) of the BAC and the change in the attention-vigilance domain T score (P = .042) were significantly improved, but there were no differences between the drug and placebo groups. The changes in the CGI-S scores were not significant, but the changes in the Clinical Impression-Improvement (CGI-I) scores showed worsening in the placebo group at week 1 (P = .032), week 2 (P = .024), week 4 (P = .024), and week 6 (P = .60) compared to baseline. The change in FIQ scores was not significant. Milnacipran may have a potential role in the improvement of pain, disability, and mood. The effect of milnacipran on cognition in fibromyalgia needs further research. ClinicalTrials.gov identifier: NCT01829243.

Comparable efficacy and safety of 8 weeks treatment with agomelatine 25–50 mg or fluoxetine 20–40 mg in Asian out-patients with major depressive disorder

ObjectiveThis randomized, double-blind study evaluates the efficacy and tolerability of agomelatine, using fluoxetine as an active comparator, in Asian patients suffering from moderate to severe major depressive disorder (MDD). MethodPatients were randomly assigned to receive either agomelatine (25–50mg/day, n=314) or fluoxetine (20–40mg/day, n=314) during an 8-week treatment period. The main outcome measure was the change in Hamilton Depression Rating Scale 17 items (HAM-D17) scores. Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness (CGI-S) and Improvement of illness (CGI-I), patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire (LSEQ) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A) scores. Tolerability and safety evaluations were based on emergent adverse events. ResultsAgomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population. Mean changes over 8 weeks were clinically relevant and similar in both groups (−14.8±7.3 and −15.0±8.1 on HAM-D17 scale in agomelatine and fluoxetine groups, respectively). The between-group difference reached statistical significance on non-inferiority test (p=0.015). Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups. The two treatments were equally effective on the symptoms of both anxiety and sleep. The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population. ConclusionsAgomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients.

Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: A pooled analysis

BackgroundA Phase 2 efficacy study suggested that asenapine (ASE) was superior to risperidone in decreasing negative symptoms in schizophrenia at 6 weeks, prompting design of two negative symptom studies. Two 26-week core studies with 26-week extensions compared asenapine (ASE: 5–10mg twice-daily] and olanzapine (OLA: 5–20mg once-daily) as monotherapies in reducing persistent negative symptoms (PNS). While neither study met the primary endpoint of superiority of ASE over OLA, ASE was statistically superior to OLA in one extension study. This prompted a pooled analysis of the treatment effects of both drugs. MethodsData were pooled from two 26-week core studies and extensions. Efficacy endpoints: change in Negative Symptom Assessment scale-16 (NSA-16) total score at Week 26 (prespecified primary endpoint) and Week 52. Additional measures: change in Positive and Negative Syndrome Scale (PANSS)-total, Marder factors, negative subscale scores, Clinical Global Impression Severity of Illness score (CGI-S) assessments, NSA-16 factor domains, NSA global score, and individual items. ResultsPooled data from the extension studies (n=502) showed no differences between ASE and OLA at Week 26. At Week 52, ASE showed superiority over OLA in NSA-16 total score, NSA global, PANSS Marder negative and PANSS negative subscales, some NSA-16 items, and four of five factor domains. In addition, pooled data for patients who entered the core trials (n=949) were analyzed over 52weeks (whether or not patients entered the extension). No significant differences between groups were observed in change in NSA-16 total score at 26-weeks. At Week 52, ASE was significantly superior over OLA in this measure, NSA global score and PANSS Marder negative factor. There were more early dropouts due to AEs, including worsening of the disease, in the ASE group. ConclusionIn this pooled analysis, ASE and OLA did not differ significantly over 26 weeks, but indicated a signal of superiority for ASE with continued treatment up to 52 weeks.

P.2.b.038 How to switch to agomelatine after an initial treatment failure of paroxetine or venlafaxine?

This randomized, double-blind study evaluates the efficacy and tolerability of agomelatine, using fluoxetine as an active comparator, in Asian patients suffering from moderate to severe major depressive disorder (MDD).Patients were randomly assigned to receive either agomelatine (25–50 mg/day, n = 314) or fluoxetine (20–40 mg/day, n = 314) during an 8-week treatment period. The main outcome measure was the change in Hamilton Depression Rating Scale 17 items (HAM-D17) scores. Secondary efficacy criteria included scores on Clinical Global Impression Severity of illness (CGI-S) and Improvement of illness (CGI-I), patient sleeping improvement using the self-rating Leeds Sleep Evaluation Questionnaire (LSEQ) and anxiety using the Hamilton Anxiety Rating Scale (HAM-A) scores. Tolerability and safety evaluations were based on emergent adverse events.Agomelatine and fluoxetine exert a comparable antidepressant efficacy in the Asian population. Mean changes over 8 weeks were clinically relevant and similar in both groups (−14.8 ± 7.3 and −15.0 ± 8.1 on HAM-D17 scale in agomelatine and fluoxetine groups, respectively). The between-group difference reached statistical significance on non-inferiority test (p = 0.015). Clinically relevant decreases in CGI-S and CGI-I scores were observed over the treatment period in both groups. The two treatments were equally effective on the symptoms of both anxiety and sleep. The good tolerability profile and safety of both doses of agomelatine was confirmed in the Asian population.Agomelatine and fluoxetine are equally effective in the treatment of MDD-associated symptoms in Asian depressed patients.

Relationship of oestrogen receptor status to depressive symptoms and quality of life in breast cancer patients.

We investigated the relationship of oestrogen receptor (ER) status to the severity of depressive symptoms and quality of life (QOL) impairment in breast cancer patients. Seventy-seven breast cancer patients with comorbid depression were evaluated with the Hamilton Depression Rating Scale (HAMD), the Clinical Global Impression-Severity of Illness (CGI-S) for depression, and the Functional Assessment of Cancer Therapy-Breast (FACT-B). ER status was determined using immunohistochemical analysis. The ER-positive group (n = 31) showed significantly higher scores compared with the ER-negative group (n = 46) on HAMD total (p = 0.04) and somatic anxiety factor (p = 0.004) scores as well as CGI-S score (p = 0.03). As for QOL measured with the FACT-B, a significantly higher score was found on the Functional Well-Being (FWB) subscale in the ER-positive group (p = 0.001). The relationships were further analysed using generalised linear models (GLM), after controlling for the influence of the current anti-oestrogen treatment. The analysis revealed that ER status was still significantly related to the FWB subscale score of the FACT-B (p = 0.04). However, the HAMD and CGI-S scores were no longer significantly related to ER status after the influence of anti-oestrogen treatment was controlled for. These results suggest that ER status, which is a well-known biological prognostic factor in breast cancer, may be related to the severity of certain aspects of depressive symptoms or QOL impairment, implying a role of the ER in affective and behavioural regulation. However, anti-oestrogen treatments significantly influence these relationships.