Clinical Global Impression-Severity Scores Research Articles

The 23-Hour Observation Unit Admissions Within the Emergency Service at a National Tertiary Psychiatric Hospital: Clarifying Clinical Profiles, Outcomes, and Predictors of Subsequent Hospitalization.

We examined health care utilization, clinical profiles (such as sociodemographic features, clinical severity), and outcomes (inpatient admission, revisit within 24 hours of discharge) of patients who were admitted to a 23-hour observation unit within the emergency service of a tertiary psychiatric hospital and hypothesized that a specific clinical profile (greater clinical severity, lower psychosocial functioning) predicted subsequent inpatient hospitalization. The medical records of all patients admitted to the observation unit from February 5, 2007, to February 4, 2012 (N = 2,158) were assessed for relevant data. Clinical severity and level of psychosocial functioning were assessed using Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, respectively. Overall, the patients seen were predominantly Chinese males > 36 years old who had diagnoses including stress-related, anxiety, affective spectrum, and psychotic disorders. The clinical severity score (CGI-S) improved significantly following discharge from the observation unit (t 1,1848 = 23.316; P < .001). Logistic regression analyses revealed that self-referred (P = .001), older patients (P = .007) with past psychiatric history (P = .019), lower GAF scores (P = .025), and less improvement of CGI-S scores (P = .001) were associated with inpatient admission after a 23-hour stay in the observation unit. Our study findings affirmed our hypothesis and supported the utility of the observation unit in monitoring the overall clinical status of patients, which was linked with subsequent inpatient admissions. Better management of these patients at the outpatient level can potentially decrease unnecessary hospitalization and reduce health care cost as well as illness burden on patients and caregivers.

The Effectiveness and Safety of Antipsychotic and Antidepressant Medications in Individuals with 22q11.2 Deletion Syndrome.

The purpose of this study was to evaluate the effectiveness and safety of antipsychotic and antidepressant medications in individuals with 22q11.2 deletion syndrome (22q11.2 DS) and psychiatric comorbidity. We used a record review, structured clinical interviews, and the Clinical Global Impressions (CGI) scale to retrospectively assess the effectiveness and safety of antipsychotic medications for schizophrenia spectrum disorders and of antidepressant medications for depressive and anxiety disorders in 40 individuals with 22q11.2DS. We observed significant improvement in CGI-Severity scores in individuals with 22q11.2DS treated with antipsychotic or antidepressant medications, and a ∼50% response rate based on the CGI-Improvement score. Adverse events were similar in types and rates to those reported in non-22q11.2 individuals treated with antipsychotics or antidepressants. Our data show that treatment with antipsychotics and antidepressants may be effective while being relatively safe in individuals with 22q11.2DS. Antipsychotic and antidepressant medications should be considered in any individual with 22q11.2DS who has a psychiatric morbidity, such as psychosis or mood or anxiety disorders. Although the psychotropic medications were generally well tolerated in our sample, more rigorous metabolic and cardiovascular measures are required in future studies to conclusively verify the safety of these medications.

Which somatic symptoms are associated with an unfavorable course in Chinese patients with major depressive disorder?

This was an analysis of the impact of somatic symptoms on the severity and course of depression in Chinese patients treated for an acute episode of major depressive disorder (MDD). Data were extracted from a 3-month prospective observational study which enrolled 909 patients with MDD in psychiatric care settings; this analysis focused on the Chinese patients (n=300). Depression severity was assessed using the Clinical Global Impression of Severity (CGI-S) and 17-item Hamilton Depression Rating Scale (HAMD-17); somatic symptoms were assessed using the patient-rated 28-item Somatic Symptom Inventory (SSI). Cluster analysis using baseline SSI scores grouped patients into three clusters with no/mild, moderate, or severe somatic symptoms. Four SSI factors (pain, autonomic symptoms, energy, and central nervous system) were defined, and regression analyses identified which factors were associated with remission at 3 months. More than 70% of the patients had moderate or severe somatic symptoms. Baseline depression severity (HAMD-17 and CGI-S scores) was associated with more severe somatic symptoms. Remission rates differed between clusters of patients: 84.1%, 72.0%, and 55.3% for no/mild, moderate, and severe somatic symptoms, respectively (P=0.0034). Pain symptoms were the somatic symptoms more strongly associated with lower remission rates at 3 months. Somatic symptoms are associated with greater clinical severity and lower remission rates. Among somatic symptoms, pain symptoms have the greatest prognostic value and should be taken into account when treating patients with depression.

Efficacy and safety of flexibly dosed paliperidone palmitate in Chinese patients with acute schizophrenia: an open-label, single-arm, prospective, interventional study.

This open-label, single-arm, multicenter, 13-week, prospective study explored the efficacy, safety, and tolerability of paliperidone palmitate (150 milligram equivalents [mg eq] [day 1], 100 mg eq [day 8], both deltoid injections; 75–150 mg eq, deltoid/gluteal injection) in Chinese patients with acute schizophrenia (Positive and Negative Syndrome Scale [PANSS] total score ≥70), who previously had unsatisfactory therapeutic effect following oral antipsychotic treatment (without washout period). Primary efficacy endpoint was percentage of patients with ≥30% improvement in the PANSS total score at the end of 13 weeks. Secondary efficacy endpoints included change from baseline to end of week 13 in PANSS total score, PANSS subscale scores, Marder factor scores, Clinical Global Impressions–Severity score, and Personal and Social Performance Scale scores. Overall, 477/610 enrolled patients (full analysis set, 78.2%) completed the study (men: 55.1%; women: 44.9%; mean age: 31.5 years). Total, 443/610 (72.6%, full analysis set) patients achieved primary endpoint (mean [standard deviation] change from baseline: –30.9 [19.51]). All secondary endpoints demonstrated significant improvement at the end of 13 weeks. One death occurred during this acute phase. The most common (>5%) treatment-emergent adverse events were extrapyramidal disorders (8.4%). The efficacy and safety data are consistent with other short-term, placebo-controlled studies of paliperidone palmitate conducted in similar populations.

Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond?

Objectives:Once-monthly intramuscular extended-release naltrexone (XR-NTX) has demonstrated efficacy for the prevention of relapse in opioid dependence, providing an alternative to agonist or partial agonist maintenance (ie, methadone and buprenorphine). The question remains, for whom is this unique treatment most efficacious and can patient-treatment matching factors be identified?Methods:A moderator analysis was conducted on a previously reported 24-week, placebo-controlled, multisite, randomized controlled trial of XR-NTX (n = 126) versus placebo (n = 124) among recently detoxified opioid-dependent adults in Russia, which showed XR-NTX superior to placebo in proportion of opioid abstinent weeks. The moderator analysis examined a dichotomous indicator of good clinical response—achieving at least 90% of weeks abstinent over the 24-week trial. A series of logistic regression models were fit for this outcome as functions of treatment (XR-NTX vs placebo), each baseline moderator variable, and their interactions. The 25 baseline variables included demographics, clinical severity (Addiction Severity Index, SF-36, and Clinical Global Impression-Severity), functioning (EQ-5D), craving, and HIV serostatus (HIV+).Results:More XR-NTX patients achieved 90% abstinence (64/126, 51%) versus placebo (39/124, 31%; P = 0.002). There were no significant interactions between baseline variables and treatment. There was a significant main effect of Clinical Global Impression-Severity score (P = 0.02), such that higher severity score was associated with a lower rate of Good Clinical Response.Conclusions:The absence of significant baseline by treatment interactions indicates that no patient-treatment matching variables could be identified. This suggests that XR-NTX was effective in promoting abstinence from opioids across a range of demographic and severity characteristics.

A 6-year open-label study of the efficacy and safety of olanzapine long-acting injection in patients with schizophrenia: a post hoc analysis based on the European label recommendation.

PurposeTo assess the long-term efficacy and safety of olanzapine long-acting injection (LAI) in the treatment of schizophrenia, focusing on clinical trial data consistent with the approved indication and dosing recommendations in the European label and which forms the basis for treatment decisions made by clinicians in daily clinical practice.Patients and methodsThis was a post hoc analysis of a 6-year open-label study of olanzapine LAI in patients (male or female, 18–75 years old) with schizophrenia entering this study following feeder studies of olanzapine LAI. Patients were flexibly dosed (45–405 mg, 2- to 4-week intervals), but those receiving oral olanzapine supplementation whose total olanzapine dose was >20 mg/day equivalent were excluded from this post hoc analysis.ResultsData from 669 patients were analyzed (44.5% completed). Positive and Negative Syndrome Scale total scores did not change significantly from baseline to endpoint; Clinical Global Impression-Severity scores improved significantly. Mean weight change was +2.19 kg (P<0.001), with 40.8% of patients experiencing ≥7% weight gain. There were 24 occurrences of post-injection delirium/sedation syndrome (PDSS).ConclusionOlanzapine LAI appeared to be effective in the long-term maintenance of schizophrenia, and the safety profile was consistent with that of oral olanzapine, except for injection-related events and PDSS events.

Relationships between global assessment of functioning and other rating scales in clinical trials for schizophrenia

The relationship between the Global Assessment of Functioning (GAF) with other scales in schizophrenia has rarely been investigated. A systematic literature search was conducted to identify articles that reported the GAF score together with scores in the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) or Brief Psychiatric Rating Scale (BPRS), using MEDLINE, EMBASE and PsycINFO, with keywords of schizophrenia, clinical trial and global assessment of functioning (last search 30 June 2013). Correlational analyses with weighting by the study participant numbers across these rating scales were performed. In 40 clinical trials (n=8000) that reported cross-sectional data on the GAF and PANSS, a significant but modest correlation was noted (Pearson׳s r=−0.401, p<0.0001). Furthermore, a correlation between the GAF and CGI-severity (CGI-S) at study baseline in 38 studies (n=11,315) was robust (r=−0.893, p<0.0001). In longitudinal studies, changes in the GAF scores were negatively correlated with those in the PANSS as well as CGI-S scores (p<0.0001 for both). Data on the BPRS were all statistically significant although relatively scarce. While optimal degree of concordance is undetermined among psychiatric scales that are presumed to be measuring different but overlapping constructs, this study found significant correlations in the GAF and CGI-S or PANSS, both cross-sectionally and longitudinally. The GAF-CGI-S relationship was especially tighter, making it a reliable clinical indicator.

Patients with schizophrenia or schizoaffective disorder who receive multiple electroconvulsive therapy sessions: characteristics, indications, and results.

BackgroundWhile electroconvulsive therapy (ECT) has been used for many years, there is insufficient research regarding the indications for continuation/maintenance (C/M)-ECT, its safety and efficacy, and the characteristics of patients with schizophrenia or schizoaffective disorder who receive multiple ECT sessions. The aims of this study were to characterize a series of patients who received 30 ECT sessions or more, to describe treatment regimens in actual practice, and to examine the results of C/M-ECT in terms of safety and efficacy, especially the effect on aggression and functioning.MethodsWe performed a retrospective chart review of 20 consecutive patients (mean age 64.6 years) with schizophrenia (n=16) or schizoaffective disorder (n=4) who received at least 30 ECT sessions at our ECT unit, and also interviewed the treating physician and filled out the Clinical Global Impression-Severity, Global Assessment of Functioning, and the Staff Observation Aggression Scale-Revised.ResultsPatients received a mean of 91.3 ECT sessions at a mean interval of 2.6 weeks. All had been hospitalized for most or all of the previous 3 years. There were no major adverse effects, and cognitive side effects were relatively minimal (cognitive deficit present for several hours after treatment). We found that ECT significantly reduced scores on the Staff Observation Aggression Scale-Revised subscales for verbal aggression and self-harm, and improved Global Assessment of Functioning scores. There were reductions in total aggression scores, subscale scores for harm to objects and to others, and Clinical Global Impression-Severity scores, these were not statistically significant.ConclusionC/M-ECT is safe and effective for chronically hospitalized patients. It improves general functioning and reduces verbal aggression and self-harm. More research using other aggression tools is needed to determine its effects and to reproduce our findings in prospective and controlled studies.

The Frequency of Demodex Spp in Depression Patients

Objective: Demodex spp., usually located on the human skin, including the face and eyelashes, is a mandatory ectoparasite. The aim of this study was to evaluate the prevalence and factors affecting Demodex spp. in patients with depression. Materials and Methods: In this study, 63 depressed patients and 63 healthy controls were evaluated. To collect samples for analysis, a drop of glue containing cyanoacrylate was put on a lamella and the lamella was pressed on the certain areas of the face (forehead, cheeks, nose, and chin) for about a minute. Then it was carefully removed and the density of Demodex spp. in a cm2 was counted under a microscope. For the diagnosis, the presence of five or more Demodex spp. in a cm2 was considered to be positive. Results: In 23.8% of depressed patients (n=15) and in 9.5% of the control group (n=6), Demodex spp. was detected in the facial area. The presence of Demodex spp. in the facial area of depressed patients was significantly higher compared to the control group. When CGI severity scores of patients and the relationship between the severity of depression and the presence of Demodex spp. were compared, no significant difference was detected. Conclusion: Depression may be a risk factor for the infection of Demodex parasites because of impaired immune system as well as reduction of self-care and hygiene of the person. For the itchy lesions on the face of depressed patients, Demodex spp. infestation should also be taken into consideration.

Clinical Global Impression-severity score as a reliable measure for routine evaluation of remission in schizophrenia and schizoaffective disorders.

AimsThis study aimed to compare the performance of Positive and Negative Syndrome Scale (PANSS) symptom severity criteria established by the Remission in Schizophrenia Working Group (RSWG) with criteria based on Clinical Global Impression (CGI) severity score. The 6-month duration criterion was not taken into consideration.MethodsA convenience sample of 112 chronic psychotic outpatients was examined. Symptomatic remission was evaluated according to RSWG severity criterion and to a severity criterion indicated by the overall score obtained at CGI-Schizophrenia (CGI-SCH) rating scale (≤3) (CGI-S).ResultsClinical remission rates of 50% and 49.1%, respectively, were given by RSWG and CGI-S, with a significant level of agreement between the two criteria in identifying remitted and non-remitted cases. Mean scores at CGI-SCH and PANSS scales were significantly higher among remitters, independent of the remission criteria adopted. Measures of cognitive functioning were largely independent of clinical remission evaluated according to both RSWG and CGI-S. When applying RSWG and CGI-S criteria, the rates of overall good functioning yielded by Personal and Social Performance scale (PSP) were 32.1% and 32.7%, respectively, while the mean scores at PSP scale differed significantly between remitted and non-remitted patients, independent of criteria adopted. The proportion of patients judged to be in a state of well-being on Social Well-Being Under Neuroleptics-Short Version scale (SWN-K) were, respectively, 66.1% and 74.5% among remitters according to RSWG and CGI-S; the mean scores at the SWN scale were significantly higher only among remitters according to CGI-S criteria.ConclusionsCGI severity criteria may represent a valid and user-friendly alternative for use in identifying patients in remission, particularly in routine clinical practice.

Efficacy and safety of vilazodone 20 and 40 mg in major depressive disorder: a randomized, double-blind, placebo-controlled trial.

Vilazodone is a selective serotonin reuptake inhibitor and 5-HT1A partial agonist approved for major depressive disorder (MDD) treatment in adults. This was a 10-week, multicenter, double-blind, placebo-controlled and active-controlled, fixed-dose trial (NCT01473381). Adult patients with MDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision criteria) were randomized 1 : 1 : 1 : 1 to vilazodone 20 or 40 mg/day, citalopram 40 mg/day, or placebo. Primary efficacy: Montgomery–Åsberg Depression Rating Scale (MADRS); secondary efficacy: Clinical Global Impressions-Severity and sustained response (MADRS total score≤12 for at least the last two consecutive double-blind visits). The intent-to-treat population comprised 1133 patients, (placebo=281; vilazodone 20 mg/day=288; vilazodone 40 mg/day=284; citalopram=280). MADRS and Clinical Global Impressions-Severity score change from baseline to week 10 was significantly greater for vilazodone 20 mg/day, vilazodone 40 mg/day, and citalopram versus placebo. Sustained response rates were numerically higher, but not significantly different, in all active treatment groups versus placebo. The most common adverse events (≥5% of vilazodone patients, twice the rate of placebo) were diarrhea, nausea, vomiting (vilazodone 40 mg/day only), and insomnia. Improved sexual function (Changes in Sexual Functioning Questionnaire scores) was seen in all groups; between-group differences were not significant. Vilazodone 20 and 40 mg/day demonstrated efficacy and tolerability in the treatment of MDD.

The efficacy and safety of once-daily quetiapine extended release in patients with schizophrenia switched from other antipsychotics: an open-label study in Chinese population.

BackgroundNon-adherence to antipsychotic medication in schizophrenic patients is common and associated with symptom relapse and poorer long-term outcomes. The risk factors for treatment non-adherence include dosing frequency and complexity. Besides, slower dose titration in an acute schizophrenic episode may lead to attenuated efficacy. Therefore, the convenient dosage regimen and rapid initiation scheme of quetiapine extended release (XR) were expected to provide better effectiveness and promote adherence in patients with schizophrenia. This study was implemented to assess the efficacy and safety of once-daily quetiapine XR in schizophrenic patients with switched from other antipsychotics which were suboptimal due to insufficient efficacy or tolerability.MethodsThis was a 12-week, open-label study conducted in the Chinese population in Taiwan.Patients who had a score of 4 (moderate) or greater on any of the 7 items of the Positive and Negative Syndrome Scale (PANSS) Positive Symptom Subscale and needed to switch from previous antipsychotics were recruited. Quetiapine XR was administered at 300 mg on day 1, 600 mg on day 2 and up to 800 mg after day 2. From day 8 until the end of the study, the dose of quetiapine XR was adjusted within 400-800 mg per day, depending on the clinical response and tolerance of the patients. The variable of the primary outcome was the change from baseline to Week 12 in PANSS total and subscale scores. Secondary outcome was the baseline-to-endpoint difference in the Clinical Global Impression-Severity (CGI-S) scores of the participants.ResultsSixty-one patients were recruited and 55.7% of them completed the study. The mean changes in the PANSS total score and CGI-S score showed significant improvement (−18.4, p < .001 and −1.0, p < .001, respectively). Four patients (6.7%) experienced adverse events including headache, exacerbation of psychosis and dysuria. The use of concomitant anticholinergics decreased from 15.0% to 8.3%.ConclusionsThe results of our investigation implicated that quetiapine XR was an effective and well tolerated alternative for Chinese schizophrenic patients with previous suboptimal treatment. Future large-scale studies are warranted to validate our results.Trial registrationClinicalTrials.gov ID NCT02142556. Registered 15 May 2014.

An open-label, flexible-dose study of paliperidone extended-release in Chinese patients with first-onset psychosis

BackgroundAntipsychotic medications facilitate the improvement of psychotic symptoms in patients with first-episode psychosis. Paliperidone extended-release (pali-ER), an atypical antipsychotic, was assessed for efficacy and safety in Chinese patients with first-episode psychosis.MethodsIn this 8-week, open-label, single-arm, multicenter study, patients with first-episode psychosis (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) and a Positive and Negative Syndrome Scale (PANSS) total score ≥70 were treated with flexible-dose pali-ER tablets (3–12 mg/day). The primary efficacy endpoint was the percentage of patients with an increase of ≥8 points in Personal and Social Performance (PSP) score from baseline to day 56 (8 weeks). Secondary endpoints included reduction in PANSS total score, improvement in Clinical Global Impression-Severity score, PSP score, Subjective Well-being under Neuroleptics Scale score, and relationship between duration of untreated psychosis and PANSS or PSP. Incidences of treatment-emergent adverse events were used to evaluate safety.ResultsOverall, 283 of 294 patients (96%) achieved a ≥8-point increase in PSP (primary endpoint, analysis set). For the secondary efficacy endpoints, 284/306 patients (93%) had a ≥30% reduction in PANSS total score; 266/306 patients (87%) achieved a ≤3 Clinical Global Impression-Severity scale score, and 218/294 patients (74%) had a PSP score ≥71. The Subjective Well-being under Neuroleptics Scale score was improved from a baseline mean of 72.7 to 94.7 at endpoint. There was a negative correlation between duration of untreated psychosis and posttreatment PSP score and a positive correlation with posttreatment PANSS total score. The most common treatment-emergent adverse events were extrapyramidal symptoms (12%), and agitation, somnolence, and xerostomia (4% each).ConclusionAn 8-week, flexible-dose (3–12 mg/day) treatment with pali-ER resulted in significant improvements in psychotic symptoms and social functioning in Chinese patients with first-episode psychosis and was generally tolerable.

Cariprazine in the treatment of acute mania in bipolar I disorder: A double-blind, placebo-controlled, Phase III trial

BackgroundThis Phase III, randomized, double-blind, placebo-controlled study investigated the efficacy and tolerability of flexibly-dosed cariprazine in patients with acute manic or mixed episodes associated with bipolar I disorder. MethodsPatients were randomized to 3 weeks of double-blind treatment with cariprazine 3–12mg/day (n=158) or placebo (n=154). The primary efficacy parameter was change from baseline to Week 3 in Young Mania Rating Scale (YMRS) total score. The secondary efficacy parameter was change from baseline to Week 3 in Clinical Global Impressions-Severity (CGI-S) score. ResultsMean change from baseline to Week 3 in YMRS total score was significantly greater for patients receiving cariprazine 3–12mg/day versus placebo (P=0.0004). Significant differences between groups in YMRS total score mean change were observed by Day 4 (first postbaseline assessment) and maintained throughout double-blind treatment (all assessments, P<0.01). Cariprazine also demonstrated statistically significant superiority over placebo on YMRS response (≥50% improvement: cariprazine, 58.9%; placebo, 44.1%; P=0.0097) and remission (YMRS total score≤12: cariprazine, 51.9%; placebo, 34.9%; P=0.0025) and mean change in CGI-S (P=0.0027) score and Positive and Negative Syndrome Scale (PANSS) (P=0.0035) total score. The most common cariprazine-related (≥10% and twice placebo) treatment emergent adverse events (TEAEs) were akathisia, extrapyramidal disorder, tremor, dyspepsia, and vomiting. Mean change from baseline in metabolic parameters were generally small and similar between groups. LimitationsLack of active comparator arm; short duration of study. ConclusionIn this study, cariprazine 3–12mg/day was effective and generally well tolerated in the treatment of manic and mixed episodes associated with bipolar I disorder.

Impact of painful physical symptoms on depression outcomes in elderly Asian patients.

ABSTRACT Background: Painful physical symptoms (PPS) are prevalent among elderly patients with depression. We describe the impact of PPS on depression outcomes and quality of life (QOL) of elderly Asian patients with major depressive disorder (MDD). Methods: This post hoc analysis of data from a three-month prospective observational study of East Asian MDD in- or out-patients focused on elderly patients aged ≥60 years. Depression severity was evaluated using the Hamilton depression (HAMD-17) and clinical global impression of severity (CGI-S) scales, while QOL was measured using EuroQOL (EQ-5D and EQ-VAS) instruments. PPS were rated using the modified somatic symptom inventory (SSI). Results: At baseline, depression was moderate to severe and 49% of the 146 elderly patients were painful physical symptom positive (PPS+). Bivariate analysis showed significant correlations between PPS and depression severity and QOL at baseline. Linear regression models showed the baseline factor most significantly associated with depression severity at three months was baseline PPS status. PPS+ patients had a mean increase of 2.87 points in their HAMD-17 rating and 0.77 points in their CGI-S score. Response and remission were significantly lower in PPS+ patients; response was 60% and remission was 40% in PPS+ patients while 82% and 66% in painful physical symptom negative (PPS-) patients. QOL at endpoint was lower in PPS+ patients. Conclusions: PPS are common in elderly Asian patients with MDD and negatively influence depression outcomes and QOL. Patients with PPS had lower QOL at baseline, lower response and remission rates, higher severity of depression, and lower QOL after three months of treatment.

P.2.f.002 The effect of EEG biofeedback on electrophysiological disturbances and symptoms in patients with depressive disorder

Background and Purpose: In EEG studies of depression, an abnormal pattern of asymmetric activity in the frontal regions from relative hyperactivity over the right frontal regions and/or relative hypoactivity over the left frontal regions has frequently been observed [1]. It has been suggested that EEG biofeedback could contribute normalization of EEG activity in depressed patient safely [2]. According to the recent paper [3], 21 clinical studies reported on EEG biofeedback treatment in patients with depressive disorders, and there have been only six original articles. The purpose of this study was to evaluate the effect of EEG biofeedback on electrophysiological disturbances and depressive symptoms in patient with depressive disorders. Method: 20 participants were recruited from July, 2009 to July, 2012 in a university hospital. Treatment protocol was twice or three times a week training of left hemisphere beta at F3 with alpha/theta training at Pz for 8 weeks. The neurocybernetics model of neurocybernetics company was used for EEG biofeedback training. In beta training, the reward band ranged from 15Hz to 18Hz. In alpha-theta training, the patients were trained to reduce the alpha level above 12 mV (peak-to-peak) while augmenting theta. The theta (5Hz-8Hz) and alpha (8Hz-12Hz) were reward bands. EEG was recorded by a complexity ver 2 of LAXTHA at 8 scalp locations according to the international 10/20 system. All placements were referenced to A1 or A2. We compared baseline and 8 week scores of Hamilton rating scale for Depression (HAM-D), Hamilton rating scale for Anxiety (HAM-A), Clinical global impression-severity (CGI-S) and we also compared before and after treatment resting state EEG. Interhemispheric alpha power asymmetry, called A score, was computed for homologous sites F3-F4. An asymmetry metric (A score) was computed for each epoch by subtracting logtransformed alpha power of the left midfrontal site from logtransformed alpha power of the right site (logR − log L). Negative A score means more depressed state. Results: Pre and post training clinical assessment reveals that there were significant improvement in HAM-D (p< 0.01), HAM-A (p< 0.01) and CGI-S score (p< 0.01). Asymmetry scores increased after training. In other words the negativity decreased after training. As alpha power inversely correlates with the activity of the corresponding brain area and the increase in the asymmetry score meant relative dominance on the left frontal area. But it was not statistically significant. Conclusion: EEG biofeedback treatment could improve depressive symptoms significantly. Also anxiety symptoms and functional impairment decreased after EEG biofeedback treatment. There are several limitations of this study such as small sample size, lack of control group. But this study demonstrates the significant effects of EEG Biofeedback in objective & subjective rating scales for adult patients with depressive disorders. Double blinded large controlled studies are needed in the future.

Analysis of potentially predictive factors of efficacy of adjunct extended-release quetiapine fumarate in patients with major depressive disorder.

Identification of predictors of treatment response in patients with major depressive disorder (MDD) may facilitate improved disease management. Data were pooled from two 6-week, double-blind, placebo-controlled studies of extended-release quetiapine (quetiapine XR; 150 or 300 mg/day) as adjunct to ongoing antidepressant therapy. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy outcomes (Week 6 Montgomery Åsberg Depression Rating Scale [MADRS] total score reduction) were evaluated in population subgroups (quetiapine XR both doses pooled, n = 616; placebo, n = 303). Baseline Clinical Global Impressions-Severity (CGI-S) score and previous depressive episodes on Week 6 MADRS total score change, and baseline MADRS individual item scores on Week 6 change in CGI-Improvement score, were also evaluated. No major differences between responders and non-responders to quetiapine XR were observed for patient characteristics or demographic and disease characteristics. No suggestion of a predictive association was found between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes. These analyses showed no major differences between responders and non-responders, and no predictive association between the parameters assessed and efficacy outcomes for adjunct quetiapine XR in patients with MDD and an inadequate response to prior antidepressant therapy.

Use of augmentation agents for treating depression: analysis of a psychiatric electronic medical record data set.

This study evaluated the relationship between patient characteristics and augmentation strategies for the treatment of major depressive disorder. This retrospective, cross-sectional study used data from a psychiatric electronic medical record database for patients with depression without psychosis or psychotic features who initiated augmentation therapy between January 2001 and June 2011. Medical records were evaluated to identify factors predicting use of specific augmentation agents, and a multivariate logistic regression model was used to assess clinical and demographic predictors of augmentation strategy. Of 3,209 patients initiating augmentation therapy for depression, 75% received augmentation with an antidepressant combination and 11% received augmentation with second-generation antipsychotics. Baseline clinical severity (Clinical Global Impressions-Severity score) most strongly and consistently predicted augmentation with second-generation antipsychotics. Treatment of patients in specialty settings with depression was often augmented with an antidepressant combination, whereas those with severe depression had an increased likelihood of augmentation with second-generation antipsychotics.

The efficacy and tolerability of cariprazine in acute mania associated with bipolar I disorder: a phase II trial.

Cariprazine, an orally active and potent dopamine D3 and D2 receptor partial agonist with preferential binding to D3 receptors, is being developed for the treatment of schizophrenia and bipolar mania. This Phase II trial evaluated the efficacy, safety, and tolerability of cariprazine versus placebo in the treatment of acute manic or mixed episodes associated with bipolar I disorder. This was a multinational, randomized, double-blind, placebo-controlled, flexible-dose study of cariprazine 3-12mg/day in patients with acute manic or mixed episodes associated with bipolar I disorder. Following washout, patients received three weeks of double-blind treatment. The primary and secondary efficacy parameters were change from baseline to Week 3 in Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Severity (CGI-S) scores, respectively. Post-hoc analysis evaluated changes on YMRS single items. In each group, 118 patients received double-blind treatment; 61.9% of placebo and 63.6% of cariprazine patients completed the study. The overall mean daily dose of cariprazine was 8.8mg/day. At Week 3, cariprazine significantly reduced YMRS and CGI-S scores versus placebo, with least square mean differences of -6.1 (p<0.001) and -0.6 (p<0.001), respectively. On each YMRS item, change from baseline to Week 3 was significantly greater for cariprazine versus placebo (all, p<0.05). A significantly greater percentage of cariprazine patients than placebo patients met YMRS response (48% versus 25%; p<0.001) and remission (42% versus 23%; p=0.002) criteria at Week 3. Adverse events (AEs) led to discontinuation of 12 (10%) placebo and 17 (14%) cariprazine patients. The most common AEs (> 10% for cariprazine) were extrapyramidal disorder, headache, akathisia, constipation, nausea, and dyspepsia. Changes in metabolic parameters were similar between groups, with the exception of fasting glucose; increases in glucose were significantly greater for cariprazine versus placebo (p<0.05). Based on Barnes Akathisia Rating Scale and Simpson-Angus Scale scores, more cariprazine than placebo patients experienced treatment-emergent akathisia (cariprazine: 22%; placebo: 6%) or extrapyramidal symptoms (parkinsonism) (cariprazine: 16%; placebo: 1%). Cariprazine demonstrated superior efficacy versus placebo and was generally well tolerated in patients experiencing acute manic or mixed episodes associated with bipolar I disorder.

Paliperidone Palmitate versus Risperidone Long-Acting Injection in Markedly-to-Severely Ill Schizophrenia Subjects

To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects. This subgroup analysis included 292 subjects with baseline Clinical Global Impressions-Severity scores of markedly ill or worse from a 13-week, randomized, double-dummy noninferiority study (NCT00589914). Subjects received either: 1) paliperidone palmitate (PP; 234 mg day 1 and 156 mg day 8 [corresponding to 150 and 100 milligram equivalents of paliperidone, respectively], both administered in deltoid muscle, followed by once-monthly flexible dosing in deltoid or gluteal muscle) and risperidone long-acting injection (RLAI)-matched placebo injections; or, 2) RLAI (25 mg, days 8 and 22; followed by biweekly flexible dosing) and PP-matched placebo injections. RLAI subjects received oral risperidone days 1-28; PP subjects received oral placebo. Because of RLAI's release profile, data through day 22 correspond to oral risperidone. Assessments included Positive and Negative Syndrome Scale (PANSS) and adverse event (AE) reports. Paired t-tests assessed within-group changes. LS mean (SE) PANSS total scores improved significantly (both p<.001) with PP and oral risperidone by day 4 (-5.0 [0.6] and -3.4 [0.6], respectively) through day 22; and with PP and RLAI through end point (-21.5 [1.9] and -18.6 [1.9], respectively). The between-group difference was significant only at day 4 (p=.006). Proportion of subjects with a .30% reduction in PANSS total score was not significantly different between the two groups at day 4 and was significantly greater with paliperidone palmitate than oral risperidone at days 15 and 22 (26.1% versus 12.7%, p=.013; 41.6% versus 32.0%, p=.048, respectively). Most common AEs (.5% in either treatment group): headache (PP 6.3% and RLAI 14.0%), insomnia (10.6% and 10.7%), somnolence (7.8% and 1.3%), akathisia (7.0% and 5.3%), schizophrenia (8.5% and 5.3%), agitation (5.6% and 2.0%), and injection site pain (5.6% and 1.3%). Using the recommended dosing regimens for PP and RLAI, both PP and oral risperidone (used during RLAI initiation) improved symptoms of schizophrenia in markedly-to-severely ill subjects at days 4-22.