Clinical Global Impression-Severity Scale Research Articles

S54. THE RELATION OF FORMAL THOUGHT DISORDER WITH COGNITIVE FUNCTIONS, GLOBAL AND SOCIAL FUNCTIONING AND QUALITY OF LIFE IN PATIENTS WITH SCHIZOPHRENIA

BackgroundFormal thought disorder (FTD) is considered to be a core syndrome of schizophrenia (SZ). Although there are few studies investigating the cognitive correlates in FTD, etiopathogenesis of this cluster of symptoms is not fully elucidated. Additionally, the impact of FTD on the global and social functioning and life satisfaction is yet unclear. The Thought and Language Disorder Scale (TALD) is a comprehensive, 30-item scale covering both positive/negative and objective/subjective FTD symptoms. Its unique four factorial structure is an excellent advantage to find out the relation between FTD dimensions and cognitive abilities, functioning and quality of life. This study aims to analyze the relationship between FTD which was assessed with TALD and cognitive functions, global, social functioning and quality of life in patients with SZ.MethodsPatients who met DSM-5 criteria for schizophrenia and aged between 18 and 65 years were recruited from the Department of Psychiatry, Hacettepe University Faculty of Medicine. The Turkish version of Thought and Language Disorder Scale (TALD-TR) was administered to detect formal thought disorder symptoms. The Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI) were used to assess psychopathology and illness severity. Cognitive functions were investigated using a neuropsychological test battery (working memory, verbal fluency, abstract thinking, executive functions and response inhibition). The Functioning Assessment Short Test (FAST) and the Social Functioning Scale (SFS) were administered to assess global and social functioning, World Health Organization Quality of Life Instrument Short Form (WHOQOL-BREF) was administered to assess quality of life.ResultsThe sample consisted of 46 patients (mean age 39.4 ± 10.8) and 39% (N=18) of the participants were females. Mean duration of education was 11.5 ± 3 years and mean duration of illness was 15 years. Partial correlation analyses, controlling for age and duration of education, showed that the Objective Positive FTD was associated with a deficit in executive functions and that the Objective Negative FTD was associated with impairment in working memory, category (semantic) verbal fluency, executive functions, abstract thinking and response inhibition. There was a significant negative correlation between Subjective Negative FTD and verbal fluency (alternation) whereas Subjective Positive FTD was correlated positively with lexical verbal fluency. Although FTD was significantly correlated positively with deficits in social, interpersonal and occupational functioning, no relation was detected between FTD and self-reported quality of life.DiscussionOur findings indicate that the multidimensional symptomatology of FTD could be the result of different cognitive impairments. In line with the literature, both objective positive and objective negative FTD were related to executive deficits. Additionally, working memory, verbal fluency, abstract thinking and response inhibition were correlated with objective negative FTD. To our knowledge, the relation between subjective FTD and verbal fluency is a novel finding in FTD research. Because of the close relationship between FTD and general /social functioning, FTD should be considered as one of the main treatment goals in schizophrenia. It could be suggested that investigating objective quality of life along with subjective assessments could better clarify the effect of FTD on patient’s life satisfaction. Comparison with healthy individuals, and future addition of neuroimaging investigations would further support the interpretation of these results.

M216. ASSOCIATIONS OF EXTRAPYRAMIDAL SYMPTOMS WITH PSYCHOTIC SYMPTOMS IN A COHORT OF HOMELESS OR PRECARIOUSLY HOUSED PERSONS WITH OR WITHOUT SCHIZOPHRENIA

BackgroundThere is considerable evidence supporting the association between extrapyramidal symptoms (EPS) and psychotic symptoms in patients with schizophrenia (SCZ). However, it is not well understood whether such an association exists in individuals without SCZ and how the association differs from those with SCZ. Our aim was to examine the associations of EPS with psychotic symptoms and compare them between SCZ and non-SCZ individuals.MethodsWe used data from a 10-year community-based study of homeless or precariously housed persons from Vancouver, Canada. Diagnosis of SCZ was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Severity of psychotic symptoms was rated using the Positive and Negative Syndrome Scale (PANSS). Severity of parkinsonism, dyskinesia, and dystonia was rated using the Extrapyramidal Symptom Rating Scale (ESRS), and akathisia using the Barnes Akathisia Rating Scale (BARS). Presence of EPS was defined as having at least moderate severity on the ESRS (i.e., ≥4 out of 8) or BARS (i.e., ≥3 out of 5) Clinical Global Impression-Severity (CGI-S) scale. Absence of EPS was defined as scoring ≤2 on the ESRS or ≤1 on the BARS CGI-S scale. Two-way analysis of covariance was performed using SCZ and EPS as independent variables and PANSS five factors (i.e., positive symptoms, negative symptoms, disorganization, excitement, and depression) as dependent variables, controlling for age, antipsychotic users, and cocaine- or methamphetamine-dependent individuals. Multiple linear regression analysis was performed for both SCZ and non-SCZ groups, controlling for the same confounding variables, to examine 1) associations of the severity of EPS subtypes with PANSS factors and 2) whether the presence of multiple EPS subtypes would be associated with increased SCZ symptoms relative to the presence of a single subtype.ResultsA total of 223 participants were included in this study (mean age: 44.1 ± 12.0 years; 76.1% male). Eighty-four participants met the diagnosis of SCZ, of whom 39 met our criteria for having EPS and 32 for not having EPS. The remaining 139 participants were not diagnosed with SCZ, of whom 50 had EPS and 72 did not. None of the participants had clinically significant dystonia. Overall, significant main effects of EPS were found for total symptoms (F1,182 = 24.4, p < 0.001), negative symptoms (F1,182 = 16.3, p < 0.001), disorganization (F1,181 = 16.6, p < 0.001), and excitement (F1,182 = 15.8, p < 0.001), but not positive symptoms or depression. The presence of EPS was associated with greater total symptoms and disorganization in both SCZ and non-SCZ groups. Significant interaction effects between SCZ and EPS were found for negative symptoms (F1,182 = 6.0, p = 0.015) and excitement (F1,182 = 3.9, p = 0.050), where the presence of EPS was associated with greater negative symptoms and excitement in SCZ participants, but not in non-SCZ participants. Consistent in both SCZ and non-SCZ groups, there were significant positive associations of the severity of 1) parkinsonism with negative symptoms, 2) dyskinesia with disorganization and total symptoms, and 3) akathisia with excitement. The presence of multiple EPS subtypes, relative to a single subtype, was not associated with significant increases in any SCZ symptoms, except a significant increase in excitement in non-SCZ participants.DiscussionThe presence of EPS is clearly associated with greater symptoms of SCZ, even in individuals without SCZ. People with SCZ may experience greater negative symptoms and excitement as a result of EPS than those without SCZ. Subtypes of EPS are distinctively associated with factors of SCZ symptoms. Future studies should elucidate the mechanisms underlying these associations.

S203. EFFECT OF LONG-ACTING INJECTIONS OF PALIPERIDONE PALMITATE ON CLINICAL AND FUNCTIONAL OUTCOMES IN PATIENTS WITH SCHIZOPHRENIA BASED ON ILLNESS DURATION

BackgroundWhile early intervention shows a better outcome in patients with schizophrenia, the benefit of early administration of long-acting injectable antipsychotics (LAI) in schizophrenia is not well-studied. Paliperidone Palmitate is one of the most frequently used LAI, and it is usually administered in the later stage of the illness than oral medication. In this study, the difference in clinical and functional improvement by illness duration after the administration of Paliperidone LAI was evaluated.MethodsPatients with schizophrenia who planned to switch their antipsychotic treatment from oral ones to once-monthly Paliperidone LAI were recruited from hospitals in South Korea from 26 July 2010 to 25 July 2017. The clinical and functional change was measured every 4 weeks with Clinical Global Impression Severity (CGI-S) scale and Personal and Social Performance (PSP) scale for 6 months after initiation of Paliperidone LAI. Compared to baseline, improvements after switching to Paliperidone LAI were analyzed based on the duration of illness (DI) (less than 3 years, 3 to 10 years, over 10 years).Results1166 participants (DI≤3 years, N=240; 3<DI≤10 years, N=442; DI>10 years, N=484) were enrolled. The change in CGI-S score was significantly different according to the DI and those with DI less than 3 years showed the most improvement in the aspect of clinical symptoms (DI, p<0.001; week, p<0.001; DI*week, p=0.013). All three groups showed significant improvements in PSP scores after the treatment with Paliperidone LAI and patients with DI less than 3 years demonstrated the highest PSP scores (DI, p<0.001; DI*week, p=0.436; week, p<0.001).DiscussionSwitching to Paliperidone LAI showed significantly better outcomes in schizophrenia patients especially with those with shorter DI. This result suggests that earlier administration of LAI in schizophrenia might lead to better clinical and functional outcomes.

T41. SAFETY PROFILE OF ADJUNCTIVE PIMAVANSERIN IN THE ENHANCE STUDY, A PHASE 3 TRIAL FOR THE POTENTIAL TREATMENT OF SCHIZOPHRENIA IN PATIENTS WITH AN INADEQUATE RESPONSE TO ANTIPSYCHOTIC TREATMENT

BackgroundMany patients with schizophrenia (SCZ) do not fully respond to antipsychotic (AP) treatment despite adherence and require augmentation, often with an AP with similar mode of action. Evidence supporting polypharmacy is limited and adding another AP increases associated risks of adverse effects, including extrapyramidal symptoms and cardiometabolic disturbances. Pimavanserin (PIM) is a highly selective serotonin 5-HT2A inverse agonist/antagonist approved for the treatment of Parkinson’s disease psychosis. The phase 3 ENHANCE study evaluated adjunctive PIM in patients with SCZ and inadequate response to their current AP. As previously reported (ACNP 2019), the primary efficacy endpoint of ENHANCE (change in Positive and Negative Syndrome Scale [PANSS] total score) did not achieve statistical significance. Other prespecified analyses did yield nominal statistical separation from placebo, including changes in PANSS Negative Symptoms subscale, and in PANSS total score for the subgroup of European patients. Here we describe key safety results.MethodsENHANCE was a 6-week, randomized, double-blind, placebo (PBO)-controlled study of adjunctive PIM in patients with SCZ and inadequate response to their prescribed AP (aripiprazole, olanzapine, risperidone, and others). Patients included were age 18–55 years with PANSS total score of ≥65 and ≤110, and scores of ≥4 on ≥2 items including delusions, hallucinatory behavior, and/or suspiciousness/persecution; Clinical Global Impression-Severity scale score ≥4 was also required. The starting dose of PIM or PBO was 20 mg daily and could be adjusted up to 34 mg or down to 10 mg daily after 1 week based on investigator discretion. Safety was evaluated in all randomized patients who received ≥1 dose of study drug.ResultsAll 396 randomized patients (PIM, n=198; PBO, n=198) were included in the safety analysis set. Treatment-emergent adverse events (TEAEs) were reported in 39.9% and 36.4% of patients in the PIM and PBO groups, respectively; most frequent TEAEs were headache (PIM 6.6%, PBO 9.1%), somnolence (PIM 6.6%, PBO 3.5%), and insomnia (PIM 5.1%, PBO 3.5%). Changes from baseline in Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Scale global clinical assessment of akathisia (GCAA), and Simpson–Angus Scale (SAS) scores were similar in the PIM and PBO groups. No patient developed dyskinesia (defined as a score ≥3 on any, or ≥2 on 2 of the first 7 AIMS items). Akathisia (GCAA score ≥2) in patients without baseline akathisia occurred in 4/186 (2.2%) patients receiving PIM and 1/189 (0.5%) receiving PBO. Parkinsonism (SAS total score >3) in patients without Parkinsonism at baseline occurred in 3/181 (1.7%) patients receiving PIM and 4/182 (2.2%) receiving PBO. No patient in either treatment arm had QTcF prolongation >500 msec or Torsades de Pointes during the study period; 2 (1.1%) patients in the PIM arm and 0 in the PBO arm had post-baseline QTcF prolongation >60 msec. Hypotension was reported in 1 patient in each treatment group; no patient had clinically important changes from baseline in blood pressure during treatment. Weight increase ≥7% from baseline was reported in 5/189 (2.6%) patients in the PIM group and 3/191 (1.6%) in the PBO group. Mean changes from baseline in PIM and PBO groups for fasting glucose were 0.07 mmol/L and 0.01 mmol/L; for triglycerides were -0.007 mmol/L and -0.136 mmoL/L, and for cholesterol were -0.10 mmol/L and -0.03 mmol/L, respectively.DiscussionResults of ENHANCE provide evidence that the addition of PIM to frequently used APs is well tolerated in patients with SCZ.

The Effects of a Traditional Chinese Medication on Children with Attention-Deficit/Hyperactivity Disorder.

Objective: This feasibility study examined the effects of a particular Traditional Chinese Medicine (TCM) herbal formula on attention-deficit/hyperactivity disorder (ADHD) and related problem behaviors. Design: A total of 79 participants aging 6-12 years consumed a granulated TCM herbal formula twice daily over a period of 3 months and underwent assessments at months 0, 3, and 6. Changes in ADHD symptoms and related behaviors were measured using the ADHD rating scale-IV (ADHD-RS-IV), child behavior checklist (CBCL), children's global sssessment scale (CGAS), as well as the clinical global impressions-severity (CGI-S) and improvement (CGI-I) scales. Results: Repeated measures mixed model analyses revealed significant differences in scores across time on all ADHD-RS-IV and CBCL subscales as well as on the CGAS, CGI-S, and CGI-I scales. Pairwise comparisons between months 0 and 3 as well as months 0 and 6 indicated significant improvements in scores. Scores also did not differ significantly between months 3 and 6. The results may suggest that this particular TCM formula possesses potential therapeutic qualities in the treatment of ADHD. Furthermore, changes in ADHD symptoms generally appear to be stable 3 months after discontinuation. However, these findings could also be attributed to placebo effects as well as reporting biases. Conclusion: This particular TCM formula may prove to be a useful adjunctive treatment for children with ADHD, and randomized controlled trials need to be conducted to evaluate its efficacy.

PND1 USE OF CLINICAL GLOBAL IMPRESSIONS-SEVERITY (CGI-S) TO ASSESS RESPONSE TO ANTIDEPRESSANT TREATMENT IN PATIENTS WITH TREATMENT-RESISTANT DEPRESSION

Montgomery-Åsberg Depression Rating Scale (MADRS), a 10-item questionnaire (each scored on a 7-point scale [0-6]) is a validated tool for physicians to determine response to antidepressant treatment and is used widely in clinical trial settings. The Clinical Global Impressions-Severity (CGI-S) scale with one question scored on a 7-point response scale is a more practical tool for clinicians in real-world practice. The appropriateness of using CGI-S-based assessment for identifying responders to short-term antidepressant treatment among patients with treatment-resistant depression (TRD) was determined by evaluating agreement with the established MADRS-based assessment of response.

Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance.

Objective: To describe the clinical characteristics of adolescents with antidepressant treatment-resistant major depressive disorder (MDD) and to examine the utility of the Antidepressant Treatment Record (ATR) in categorizing treatment resistance in this population. Methods: Adolescents with treatment-resistant MDD enrolled in an interventional study underwent a baseline evaluation with the ATR, Children's Depression Rating Scale-Revised (CDRS-R), and Clinical Global Impressions-Severity (CGI-S) scales. Demographic and clinical characteristics were examined with regard to ATR-defined level of resistance (level 1 to ≥3) using analysis of variance and χ2 tests. Results: In adolescents with treatment-resistant MDD (N = 97), aged 12-21 years, most were female (65%), white (89%), and had recurrent illness (78%). Patients were severely ill (median CGI-S score of 5), had a mean CDRS-R score of 63 ± 10, and 17.5% had been hospitalized for depression-related symptoms. Fifty-two patients were classified as ATR 1, whereas 32 were classified as ATR level 2 and 13 patients as ≥3, respectively. For increasing ATR-defined levels, illness duration increased from 12.0 (range: 1.5-31.9) to 14.8 (range: 1.8-31.7) to 19.5 (range: 2.5-36.2) months and the likelihood of treatment with serotonin norepinephrine reuptake inhibitors (SNRIs) and dopamine norepinephrine reuptake inhibitors (DNRIs) similarly increased (p = 0.006 for both SNRIs and DNRIs) as did the likelihood of treatment with mixed dopamine serotonin receptor antagonists (χ2 = 17, p < 0.001). Conclusions: This study underscores the morbidity and chronicity of treatment-resistant MDD in adolescents. The present characterization of related clinical features describes the use of nonselective serotonin reuptake inhibitors in adolescents with treatment-resistant depression and raises the possibility that those with the greatest medication treatment resistance are less likely to have had recurrent episodes. The study also demonstrates the utility of the ATR in categorizing treatment resistance in adolescents with MDD.

Treatment of Children and Adolescents with Epilepsy with Atomoxetine.

Objective The objective of this study was to assess the effectiveness and safety of atomoxetine in Korean children and adolescents with epilepsy. Methods We retrospectively reviewed the electronic medical records of 105 children and adolescents with epilepsy treated with atomoxetine. Effectiveness was measured with the Clinical Global Impressions-Severity (CGI-S) and/or Clinical Global Impressions-Improvement (CGI-I) scales at baseline, and after 4 and 12 weeks. We defined response to atomoxetine as a CGI-I score less than three at week 12. Safety was evaluated at each visit, based on clinical assessment by a child and adolescent psychiatrist and reports from participants or their caregivers. Results In total participants (n=105), 33 (31.4%) showed a response to treatment: a significant decrease in CGI-S scale score was observed over 12 weeks of atomoxetine treatment. The most common adverse event (AE) was decreased appetite (n=16, 15.2%), and life-threatening AEs were not observed. Seizure aggravation due to atomoxetine was observed in 7.6% (n=8) of total participants, and one of them discontinued atomoxetine. Conclusion Our results provide preliminary evidence of the effectiveness and safety of atomoxetine in children and adolescents with epilepsy.

A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia

BackgroundAn oral compound, SEP-363856, that does not act on dopamine D2 receptors but has agonist activity at trace amine–associated receptor 1 (TAAR1) and 5-hydroxytryptamine type 1A (5-HT1A) receptors, may represent a new class of psychotropic agent for the treatment of psychosis in schizophrenia.MethodsWe performed a randomized, controlled trial to evaluate the efficacy and safety of SEP-363856 in adults with an acute exacerbation of schizophrenia. The patients were randomly assigned in a 1:1 ratio to receive once-daily treatment with SEP-363856 (50 mg or 75 mg) or placebo for 4 weeks. The primary end point was the change from baseline in the total score on the Positive and Negative Symptom Scale (PANSS; range, 30 to 210; higher scores indicate more severe psychotic symptoms) at week 4. There were eight secondary end points, including the changes from baseline in the scores on the Clinical Global Impressions Severity (CGI-S) scale and the Brief Negative Symptom Scale (BNSS).ResultsA total of 120 patients were assigned to the SEP-363856 group and 125 to the placebo group. The mean total score on the PANSS at baseline was 101.4 in the SEP-363856 group and 99.7 in the placebo group, and the mean change at week 4 was −17.2 points and −9.7 points, respectively (least-squares mean difference, −7.5 points; 95% confidence interval, −11.9 to −3.0; P=0.001). The reductions in the CGI-S and BNSS scores at week 4 were generally in the same direction as those for the primary outcome, but the results were not adjusted for multiple comparisons. Adverse events with SEP-363856 included somnolence and gastrointestinal symptoms; one sudden cardiac death occurred in the SEP-363856 group. The incidence of extrapyramidal symptoms and changes in the levels of lipids, glycated hemoglobin, and prolactin were similar in the trial groups.ConclusionsIn this 4-week trial involving patients with an acute exacerbation of schizophrenia, SEP-363856, a non–D2-receptor-binding antipsychotic drug, resulted in a greater reduction from baseline in the PANSS total score than placebo. Longer and larger trials are necessary to confirm the effects and side effects of SEP-363856, as well as its efficacy relative to existing drug treatments for patients with schizophrenia. (Funded by Sunovion Pharmaceuticals; ClinicalTrials.gov number, NCT02969382.)

Prevalence and related factors of suicide attempts in first-episode and untreated Chinese Han outpatients with psychotic major depression

BackgroundMajor depressive depression (MDD) is often accompanied by suicidal behavior. Increasing evidence shows that MDD patients display psychotic symptoms. However, the relationship between psychotic symptoms and suicide attempt in MDD has not been reported. Therefore, this study was to identify the prevalence and associated factors of suicide attempts in first-episode and untreated Chinese Han outpatients comorbid with psychotic major depression (PMD). Methods1718 first-episode and untreated MDD outpatients were assessed with Positive Symptom Scale of Positive and Negative Syndrome Scale (PANSS), the 17-item Hamilton Depression Scale, Hamilton Anxiety Scale, and clinical global impression of severity scale (CGI-S). Some glycolipid metabolism and thyroid hormone parameters were measured. ResultsIn MDD patients, the percentage of PMD was 10.0%. The incidence of attempted suicide in PMD patients was 51.5%, which was more than 3 times higher than that in non-PMD patients (16.7%). In PMD patients, compared to non-attempters, suicide attempters were older, had a longer course of disease, scored higher on all scales, as well as had higher levels of thyroid stimulating hormone (TSH), thyroid peroxidases antibody, anti-thyroglobulin and blood glucose. PANSS positive symptom, CGI, diastolic blood pressure and TSH were independently associated with suicide attempts of PMD. ConclusionsPMD patients have a higher prevalence of suicide attempt than non-PMD patients. Some demographic and clinical parameters are relevant factors for suicide attempt in PMD patients.

Effect of Omega-3 and Korean Red Ginseng on Children with Attention Deficit Hyperactivity Disorder: An Open-Label Pilot Study.

ObjectiveThe purpose of the present study was to evaluate the efficacy of omega-3 and Korean red ginseng on improving attention deficit hyperactivity disorder (ADHD) symptoms and cognitive function in children with ADHD.MethodsA total of 40 children aged 6 to 12 years diagnosed with ADHD participated in this open-label trial. Participants received daily supplements containing 500 mg of omega-3 (eicosapentaenoic acid, 294 mg; docosahexaenoic acid, 206 mg) and 3 mg of Korean red ginseng extract (combination of ginsenoside Rg1, Rb1, and Rg3) for 12 weeks. No psychotropic drug was allowed during the study period. ADHD symptoms were assessed using the ADHD Rating Scale (ADHD-RS) and Clinical Global Impression-Severity (CGI-S) scale. Neuropsychological tests on sustained attention, short-term memory, and executive function were also assessed.ResultsAfter 12 weeks, participants showed significant improvements on ADHD-RS (31.12 ± 8.82 at baseline, 24.15 ± 11.45 at endpoint; p < 0.001) and CGI-S (3.38 ± 1.18 at baseline, 2.94 ± 1.00 at endpoint; p < 0.001). On the Continuous Performance Test, commission errors significantly decreased, while reaction time significantly increased. Immediate recall and delayed recall on both Auditory Verbal Learning Test and Complex Figure Test showed significant improvements. Scores of Color–Word Task from Stroop Color–Word Test also showed significant improvements after the treatment. The supplement was well tolerated.ConclusionThe results of this pilot study suggest that the combination of omega-3 and Korean red ginseng may improve ADHD symptoms and cognitive function including attention, memory, and executive function in children with ADHD. Future randomized placebo-controlled trials with a larger sample is warranted.

Sex differences in the prevalence and clinical correlates of hyperhomocysteinemia in patients with bipolar disorder.

Sex differences in bipolar disorder are well recognized but little attention has been paid to sex differences in homocysteine or hyperhomocysteinemia in bipolar patients. This study compared gender differences in homocysteine levels and rates of hyperhomocysteinemia in Chinese inpatients with bipolar disorder. A total of 198 BD patients and 84 healthy controls were enrolled. The Young Mania Rating Scale, Hamilton Depression Rating Scale, and the Clinical Global Impressions-Severity scale were used to assess the affective symptomatology. Fasting plasma Hcy levels were measured by high-performance liquid chromatography. Men had higher homocysteine levels than women and the prevalence of hyperhomocysteinemia in male patients was approximately twice that in female patients. Logistic regression analyses showed that HHcy was associated with less frequent use of valproate in males and being overweight in females. Further correlation analysis and multivariate regression analysis demonstrated that Hcy levels were inversely correlated with valproate treatment in men and positively associated with overweight in women. In bipolar patients, there are significant differences between sexes in the levels of homocysteine and prevalence of hyperhomocysteinemia. This appears to be associated with lower prevalence of valproate prescribing in men and with being overweight in women.

Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients.

BackgroundBrain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, and its dysregulation has been associated with the pathogenesis of mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone which is also produced as a cytokine by immune cells and could be a neurotrophic factor regulating the functional activity of stress-related mechanisms.AimTo investigate the possible relationship between depressive state and BDNF and PRL genotypes or levels with special reference to severity of depression.MethodsParticipants of 18–70 years with a clinical diagnosis of depressive disorder of at least moderate severity were included. These patients had not been treated with antidepressant drugs before admission to hospital during the preceding period of the last 6 months, and 54.5% had never been treated with antidepressant drugs during their entire life. The DNA was genotyped for rs1341239 within the prolactin and for rs6265, rs7124442, and rs11030104 within the BDNF gene. Rs11030104 violated the Hardy-Weinberg equilibrium distribution and was excluded from further analyses. BDNF and prolactin concentration was measured in serum by MAGPIX multiplex analyzer (Luminex, USA) using MILLIPLEX® MAP kit (Merck, Germany). Genetic associations were determined by sequentially regressing prolactin, BDNF, 17-items Hamilton's Depression (HAMD-17) and Clinical Global Impression scale, Severity (CGI-S) ratings, and depression (absent/present) on the available SNPs. Genetic associations were evaluated assuming an additive model.ResultsA total of 186 depressed patients (of which 169 were women) and 94 healthy controls (67 women) were genotyped. After excluding subjects without genetic information on all three study SNPs, 217 remained of whom 138 suffered from depression. Within depressed patients we observed an association of rs6265 with HAMD-17: mean difference (MD) 2.33 (95%CI 0.49; 4.16; p = 0.014) and CGI-S: MD 0.38 (95%CI 0.09; 0.66; p = 0.011). No significant association was observed between the prolactin SNP rs1341239 and prolactin levels. Similarly the mean differences of BDNF SNPs did not show an association with BDNF: rs6265 −0.042 ln(pg/ml) (95%CI −0.198; 0.113), and rs7124442 0.006 ln(pg/ml) (95%CI −0.117; 0.130). No other association reached statistical significance.ConclusionWe observed a significant association between BDNF gene variant rs6265 and the severity of depression in newly admitted, antidepressant treatment-free, depressed patients. Actual PRL and BDNF levels were not elevated sufficiently in depressed patients to reach statistical significance and were not associated with the studied genotypes.

Once-Monthly Long-Acting Injectable Aripiprazole for the Treatment of Patients with Schizophrenia and Co-occurring Substance Use Disorders: A Multicentre, Observational Study.

AimTo evaluate the efficacy and impact of long-acting injectable (LAI) aripiprazole in patients with schizophrenia with a coexisting substance use disorder (SUD).Patients and methodsA multicenter, observational, descriptive and retrospective study was conducted in patients with a DSM-5 diagnosis of schizophrenia who had a coexisting SUD and were treated with LAI-aripiprazole. Disease severity was evaluated with the Clinical Global Impression (CGI) severity scale for schizophrenia, daily functioning and disability were evaluated with the World Health Organisation Disability Assessment Scale (WHODAS-2.0), and the severity of the addiction was evaluated with the Severity of Dependence Scale (SDS).ResultsThe sample included 40 patients. Overall, after 6 months of treatment with LAI-aripiprazole at a dose of 400 mg/4 weeks in 77.5% of the patients, we observed significant improvement in the psychopathological symptoms, with a reduction of over 30% in the scores of the five CGI-severity scales. The WHODAS-2.0 mean (standard deviation) score was also significantly reduced from 57.6 (8.2) to 42.3 (4.3) points (p < 0.001). Regarding SUDs, after 6 months of treatment, substance use was stopped in 5 of the 9 patients with cocaine use disorder and in 3 of the 16 patients with alcohol abuse disorder. A significant reduction in the severity of the dependence was observed only in the subgroups of participants with cocaine and alcohol use disorders.ConclusionOur study suggests that once-monthly LAI-aripiprazole retains its antipsychotic efficacy in patients with schizophrenia and a coexisting SUD and could be useful for the management of cocaine or alcohol use disorders in this population.

A visual analogue scale companion for the six‐item Hamilton Depression Rating Scale

ObjectiveThe six‐item Hamilton Depression Rating Scale (HAMD6) is a clinician rated measure which lacks a self‐report companion. We explored whether a six‐item client rated visual analogue scale (VAS6) based on the HAMD6, was a consistent and valid measure of depression and useful for clinical practice.MethodParticipants were N = 117 participants, 88 (75%) female, with major depressive disorder (MDD) who received transcranial magnetic stimulation (TMS). Pre‐ and post‐treatment a trained clinician completed the HAMD6 and Clinical Global Impression Scale for Severity (CGI‐S), and patients the self‐reported VAS6.ResultsVAS6 internal consistency using Cronbach's alpha was 0.87. VAS6‐HAMD6/GGI‐S spearman correlations were moderate‐strong for four items (depressed mood; work/activities; feelings of guilt; anxiety) and the total score and weak for two items (somatic symptoms, retardation).ConclusionsThe self‐reported VAS6 was a valid measure of core aspects of depression measured by the HAMD6. It is cost effective (takes relatively little clinician time) and is a useful companion to the clinician reported HAMD6.

Effectiveness analysis of antipsychotics in schizophrenia using psychometric scales: an observational study

Background: Schizophrenia is a commonest and one of the well known psychiatric disorders. Life expectancy of a patient with schizophrenia may be 20 to 30 years shorter than the general population. Long term antipsychotic therapy is usually required for the management of schizophrenia. It is not currently possible to predict which antipsychotic may be optimal for a given patient because there are still many debates about effectiveness and efficacy of atypical drugs over first generation antipsychotics. So, our aim is to assess the effectiveness of various antipsychotics by using various psychometric scales, which will be helpful to bring out better treatment options for schizophrenia patients.Methods: This was an observational questionnaire based study, conducted on patients of inpatient and outpatient Department of Psychiatry and Department of Pharmacology at VIMSAR, Burla, for a period of 24 months (September 2015 to August 2017). Patients of schizophrenia aged 18 years or above were subjected to clinical global impression – severity scale (CGI-S) and clinical global impression – improvement scale (CGI-I) questionnaire after taking informed consent. Then scores were calculated using non parametric test with Graph pad Prism version 6.0.Results: Out of the 90 cases, majority (60) of patients belonged to the middle (25 to 45 yrs) age group followed by 20 younger (&lt;25 yrs) age group and rest 10 were elderly (&gt;45 yrs) patients. Both scales showed significant improvement with atypical antipsychotics as compared to first generation antipsychotics.Conclusions: Based on these findings, we can conclude that atypical antipsychotics are more effective than first generation antipsychotics. But further studies are needed to assist clinicians in making optimum treatment decisions.

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

BackgroundInflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15–25 years).MethodsYoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15–25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12.ResultsAt the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (− 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (− 4.2, 95% CI (− 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12.ConclusionsThe addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression.Trial registrationAustralian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.

Aripiprazole Long-Acting Injection During First Episode Schizophrenia—An Exploratory Analysis

Background: Long-acting injectable (LAI) aripiprazole was found to be efficacious in schizophrenia. In common clinical practice, the use of LAIs is often restricted to chronic patients with frequent relapses and poor adherence. Recently, some investigators advanced the idea of early LAI use also in young people with schizophrenia at their first psychotic episode (FEP). Objective: Our study aimed to assess the effect of LAI aripiprazole once monthly (AOM) in the treatment of FEP in patients aged 18–26 years. Methods: We included 50 patients with DSM-5 schizophrenia as assessed with SCID, and used the Clinical Global Impressions Scale-Severity of Illness (CGI-S) and the Positive and Negative Syndrome Scale (PANSS) to assess symptom severity and the World Health Organization Quality of Life (WHOQOL), the Short Form Health Survey (SF-36) and the Personal and Social Performance Scale (PSP) to assess quality of life (QoL) and global health perception at baseline and 3, 6, 9, and 12 months after the first AOM injection. Results: AOM was associated with a progressive improvement, compared to baseline, of both positive (p < 0.001) and negative (p < 0.001) symptoms and in general psychopathology (p < 0.001) and decrease in global severity (p < 0.001). We also observed progressive improvement in QoL and social and personal functioning. Treatment adherence was 78% at study endpoint. Our results support that AOM may improve psychotic symptoms, QoL and social functioning in young FEP patients. Further studies should compare AOM to its oral formulation in the treatment of young patients with schizophrenia at the outset of their illness.

Minimum clinically important differences for the Functioning Assessment Short Test and a battery of neuropsychological tests in bipolar disorders: results from the FACE-BD cohort.

Establishing the minimum clinically important difference (MCID) in functioning and cognition is essential to the interpretation of the research and clinical work conducted in bipolar disorders (BD). The present study aimed to estimate the MCID for the Functioning Assessment Short Test (FAST) and a battery of neuropsychological tests in BD. Anchor-based and distributive methods were used to estimate the MCID for the FAST and cognition using data from a large, multicentre, observational cohort of individuals with BD. The FAST and cognition were linked with the Clinical Global Impressions Scale-Severity (CGI-S) and Global Assessment of Functioning (GAF) using an equipercentile method. The magnitude of the standard error measurement (s.e.m.) provided another estimate of the MCID. In total, 570 participants were followed for 2 years. Cross-sectional CGI-S and GAF scores were linked to a threshold ⩽7 on the FAST for functional remission. The MCID for the FAST equalled 8- or 9-points change from baseline using the CGI-S and GAF. One s.e.m. on the FAST corresponded to 7.6-points change from baseline. Cognitive variables insufficiently correlated with anchor variables (all ρ <0.3). One s.e.m. for cognitive variables corresponded to a range of 0.45 to 0.93-s.d. change from baseline. These findings support the value of the estimated MCID for the FAST and cognition and may be a useful tool to evaluate cognitive and functional remediation effects and improve patient functional outcomes in BD. The CGI-S and GAF were inappropriate anchors for cognition. Further studies may use performance-based measures of functioning instead.

Prevalence and predictors of family accommodation in obsessive-compulsive disorder in an Indian setting.

Background:Family accommodation (FA) is a phenomenon whereby caregivers assist/facilitate rituals or behaviors related to obsessive–compulsive disorder (OCD). FA, however, has been explored primarily in the Western population, and it is unclear to what extent it might be present in diverse cultural settings. At present, little is known about the extent and predictors of FA among caregivers of adult OCD patients in India.Aims:The study aims to assess the extent, clinical correlates, and predictors of FA in the caregivers of adults with OCD.Settings and Design:Cross-sectional study conducted in an outpatient setting in a tertiary-care hospital.Materials and Methods:Hundred and one adult patients of either gender with Diagnostic and Statistical Manual of Mental Disorders-5 diagnosis of OCD and 101 caregivers were included. The patients were assessed using Yale–Brown Obsessive Compulsive Scale (YBOCS), Hamilton Rating Scale for Depression (HAM-D), World Health Organization Disability Assessment Schedule Version 2.0 12-item version (WHO-DAS 2.0.12), Clinical Global Impressions Scale for Severity (CGI-S), and Clinical Global Impressions Scale for Improvement. The FA Scale-Self Rated Version (FAS-SR) was applied on caregivers after Hindi translation.Statistical Analysis:Descriptive statistics, group comparisons, and Pearson's product moment correlations were carried out. Multiple linear regression modeling was performed with the total FAS-SR score as the dependent variable.Results:About 92% of caregivers displayed at least some form of FA. Higher scores on HAM-D, YBOCS, WHODAS, and CGI-S were associated with higher scores on FAS-SR scale, which reached statistical significance (P < 0.01).Conclusions:FA in OCD appears to be a frequent phenomenon. Higher FA is associated with higher symptom severity and disability, emphasizing its clinical and research relevance for future studies.