Clinical Global Impression-Severity Scores Research Articles

A phase 3, multicenter study to assess the 1-year safety and tolerability of a combination of olanzapine and samidorphan in patients with schizophrenia: Results from the ENLIGHTEN-2 long-term extension

AimA combination of olanzapine and samidorphan (OLZ/SAM) is in development for the treatment of patients with schizophrenia or bipolar I disorder and is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. This 52-week open-label extension (NCT02873208; ENLIGHTEN-2-EXT) assessed the long-term safety and tolerability of OLZ/SAM in patients with schizophrenia. MethodsPatients completing the 24-week randomized, double-blind, phase 3 ENLIGHTEN-2 study (NCT02694328) comparing weight change from baseline to week 24 with OLZ/SAM versus olanzapine were eligible to enroll in the 52-week ENLIGHTEN-2-EXT study. Assessments included adverse events (AEs; each visit), weight/waist circumference (every other week for the first 8 weeks, then every 4 weeks thereafter), metabolic laboratory parameters (weeks 4, 12, 24, 36, and 52), Positive and Negative Syndrome Scale (PANSS) scores (weeks 2, 4, 8, 12, 24, 36, and 52), and Clinical Global Impression-Severity (CGI-S) scores (weeks 2 and 4, then every 4 weeks thereafter through week 48, and at week 52). Analyses were based on observed results using descriptive statistics. Baseline was relative to the first OLZ/SAM dose in the extension study. ResultsIn total, 265 patients were enrolled and received at least 1 dose of OLZ/SAM; 167 (63.0%) completed the 52-week extension study. Common AEs (≥5%) were weight decreased (n = 23; 8.7%), extra dose administered (n = 21; 7.9%), headache (n = 18; 6.8%), and weight increased (n = 16; 6.0%). At week 52, the mean (SD) change from baseline for weight and waist circumference was −0.03 (6.17) kg and − 0.35 (6.12) cm, respectively. Changes in fasting lipid and glycemic parameters were generally small and remained stable over 52 weeks. During the extension, PANSS total scores remained stable, and at week 52, 81.3% of patients had CGI-S scores of 3 or less, reflecting mild illness severity. ConclusionsOLZ/SAM was generally well tolerated over 52 weeks. Weight, waist circumference, metabolic laboratory parameters, and schizophrenia symptoms remained stable throughout the study.

Efficacy of Lurasidone in Antipsychotic-Naive vs. Antipsychotic-Exposed Adolescents with Schizophrenia: Post-Hoc Analysis of a Two-Year, Open-Label Study

Few studies have examined treatment response in adolescents with schizophrenia who are treatment-naive; and there is no placebo-controlled study that we are aware of in first episode treatment-naive patients with schizophrenia. The aim of this analysis was to evaluate the long-term efficacy of lurasidone in antipsychotic-naive adolescents with schizophrenia. Patients aged 13-17 years with schizophrenia, and a PANSS total score ≥70 and <120, were randomized to 6 weeks of double-blind (DB) treatment with lurasidone (40 or 80 mg/day) or placebo. Six-week completers were eligible to enroll in a 2-year open-label extension phase receiving lurasidone flexibly dosed from 20-80 mg/day. In a post-hoc analysis, efficacy was evaluated for 2 patient groups based on treatment status prior to entering the initial 6-week DB study (treatment naïve [TN] vs. treated previously [TP]). Treatment-naïve was defined as never having received antipsychotic treatment. Efficacy measures included the PANSS total score and the Clinical Global Impression, Severity (CGI-S) score. Level of functioning was assessed using the Children's Global Assessment Scale (CGAS), with a score of 70 representing normative levels of functioning. A total of 50 TN and 221 TP patients completed the 6-week DB study and entered the extension study; and 30 (60.0%) TN and 126 (57.0%) TP patients completed 104 weeks. During the initial 6 weeks of DB treatment, mean change in PANSS total score at endpoint was greater for lurasidone vs. placebo in both the TN group (-25.0 vs. -14.4; P<0.02; effect size, 0.75), and in the TP group (-17.3 vs. -10.0; P<0.001; effect size, 0.45). During OL extension phase treatment with lurasidone, mean change from DB baseline in the PANSS total score for TN and TP patients, at week 52 was -32.6 (n=38) and -28.1 (n=151), respectively; and at week 104 was -33.6 (n=30) and -29.2 (n=126), respectively. Mean change from DB baseline in CGI-S score at both weeks 52 and 104 was -1.8 for TN patients and -1.5 for TP patients. At DB baseline mean CGAS scores indicated significant functional impairment in both the TN and TP patients (CGAS=48 and 43, respectively). During OL treatment with lurasidone, mean change (from DB baseline) in the CGAS score at Weeks 52 and 104, respectively, was +22.0 and +22.9 in TN patients, and +21.1 and +22.9 in TP patients. During OL treatment with lurasidone, mean observed change from DB baseline in the weight (in kg,) at Weeks 52 and 104, respectively, was +4.2 and +4.8 in TN patients, and +4.0 and +5.0 in TP patients. These weight increases are consistent with expected weight gains in adolescents during a 2-year period (based on CDC growth charts). In this post-hoc analysis of a 2-year study, adolescents with schizophrenia who had received no previous antipsychotic therapy showed greater improvement compared to previously treated patients during both short- and long-term treatment with lurasidone. Sunovion Pharmaceuticals Inc.

Evaluation of MADRS Severity Thresholds in Patients With Bipolar Depression

AbstractIntroductionThe Montgomery-Åsberg Depression Rating Scale (MADRS) is commonly used for the assessment of depressive symptom changes in patients with major depressive disorder (MDD) or bipolar depression. Categories of depression severity that correspond to ranges of MADRS total score have been previously reported in patients with MDD, but it appears that MADRS severity ranges have not been reported for patients with bipolar I disorder. The objective of this study was to evaluate MADRS total score ranges that correspond with different grades of depression severity in patients with bipolar I depression.MethodsData were pooled from 3 randomized, double-blind, placebo-controlled, 6- or 8-week trials of cariprazine in patients with bipolar I depression. MADRS severity ranges were evaluated using an anchor-based approach with the clinician-rated, 7-category Clinical Global Impression-Severity (CGI-S) scale. CGI-S has previously been used to determine severity thresholds in MDD. Correlations between MADRS total score and CGI-S score were assessed in the pooled dataset at week 6; placebo and active treatment arms were pooled together. Youden index from receiver operating characteristic (ROC) curves was used to determine the optimal threshold for MADRS total score corresponding to each CGI-S severity level.ResultsThe pooled dataset included 1523 patients with bipolar depression. Mean CGI-S scores were highly correlated with mean MADRS total scores at week 6 (r=.87; P&lt;.0001), with MADRS total scores increasing with CGI-S severity. Using the ROC curves, MADRS total score ranges corresponding to each CGI-S severity category were estimated as follows: score of 0-6 for “normal, not at all ill”, 7-12 for “borderline mentally ill”, 13-18 for “mildly ill”, 19-23 for “moderately ill”, 24-36 for “markedly ill”, 37-39 for “severely ill”, and 40 or greater for “extremely ill”. Area under the curve (AUC) values for these cutoffs ranged from 0.930 to 0.997, representing outstanding sensitivity and specificity.ConclusionsUtilizing data from 3 recent clinical trials of subjects with bipolar depression, we were able to identify MADRS severity thresholds. These empirical findings may help clinicians to understand and contextualize MADRS results from bipolar clinical research and apply to their patients in practice.FundingAbbVie Inc.

Management of the Pseudobulbar Affect (PBA) in Kabuki Syndrome combined dextromethorphanfluoxetine treatment as an alternative to dextromethorphan/quinidine

A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global ImpressionImprovement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) – especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It’s could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary.

Illness Severity Moderated Association Between Trait Anxiety and Amygdala-Based Functional Connectivity in Generalized Anxiety Disorder.

Trait anxiety is considered a vulnerability factor for the development of generalized anxiety disorder (GAD). The amygdala is related to both trait anxiety and GAD. Thus, we investigated amygdala-based functional connectivity (FC) in drug-naive non-comorbid GAD patients and explored its associations with personality, symptoms, and illness severity. FC analyses using the bilateral amygdala as seeds were performed with resting-state functional MRI data from 38 GAD patients and 20 matched healthy controls (HCs). Clinical characteristics were correlated with FC Z-scores from regions showing significant group differences. Furthermore, moderation analyses were used to explore the conditional effect of illness severity measured by the Clinical Global Impression–Severity (CGI-S) scale on the relationship between FC and trait anxiety. Relative to HCs, GAD patients showed hypoconnectivity between the amygdala and the rostral anterior cingulate cortex (rACC), inferior frontal gyrus (IFG), parahippocampal gyrus, and cerebellum and hyperconnectivity between the amygdala and the superior temporal gyrus (STG), insula, and postcentral gyrus. In GAD patients, amygdala–rACC connectivity was negatively associated with symptom severity and trait anxiety, and amygdala–IFG connectivity was positively associated with symptom severity. Moreover, CGI-S scores moderated the negative correlation between trait anxiety and amygdala–rACC FC. We demonstrate that there is extensive amygdala-based network dysfunction in patients with GAD. More importantly, amygdala–rACC connectivity plays a key role in the neural pathology of trait anxiety. Finally, the more severe the illness, the stronger the negative association between trait anxiety and amygdala–rACC FC. Our results emphasize the importance of personalized intervention in GAD.

Dasotraline in adults with attention deficit hyperactivity disorder: a placebo-controlled, fixed-dose trial.

In a previous study, dasotraline demonstrated efficacy at a dose of 8 mg/day in adults with attention deficit hyperactivity disorder (ADHD). The aim of the current study was to evaluate the efficacy and safety of dasotraline in doses of 4 and 6 mg/day. Adults meeting Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for ADHD were randomized to 8 weeks of double-blind, once-daily, fixed-dose treatment with dasotraline 4 mg/day, 6 mg/day, or placebo. The primary efficacy endpoint was changed in the ADHD Rating Scale, Version IV (ADHD RS-IV) total score. Secondary efficacy endpoints included the Clinical Global Impression, Severity (CGI-S) Scale. Least squares mean reduction at week 8 in the ADHD RS-IV HV total score was not significantly greater (vs. placebo) in the dasotraline 4 mg/day group (-15.0 vs. -13.9; n.s.; or in the dasotraline 6 mg/day group (-16.5 vs. -13.9; P = 0.074; Hochberg correction). Treatment with dasotraline 6 mg/day was significant at week 8 (uncorrected) on the ADHD RS-IV total score (P = 0.037) and the CGI-S score (P = 0.011). Treatment with the 4 mg/day dose of dasotraline was NS. Treatment with dasotraline was generally well tolerated. The results provide additional evidence that supports the potential efficacy of dasotraline, in doses of 6 mg/day, in adults with ADHD.

Electroconvulsive Therapy for Bipolar Depression in Older Adults.

Electroconvulsive therapy (ECT) is a well-established treatment for mood disorders in younger adults and has been consistently shown to be safe and effective in unipolar depression in older adults. However, data on this treatment in older adults with bipolar disorder are limited. In this retrospective study, we report outcomes from all cases of older adults with bipolar depression who received ECT from a large academic institution over a 7-year period. We retrospectively identified all patients 65 years and older with bipolar depression who were treated with ECT over a 7-year period. Patients receiving ECT for an episode of bipolar depression were included in the study based on chart review and availability of documented outcome measures. Primary outcomes were changes in Montreal Cognitive Assessment and Clinical Global Impressions scores. We identified 34 patients meeting inclusion criteria. Collectively, patients had statistically significant improvement in Montreal Cognitive Assessment scores and reductions in Clinical Global Impressions severity scores after treatment. Pre- and posttreatment Montgomery-Asberg Depression Rating Scale scores were also available for a subset of 20 patients and demonstrated a similarly significant reduction in severity with treatment. There were no serious adverse effects of treatment, and no patients discontinued treatment. Electroconvulsive therapy was well tolerated and effective in treating bipolar depression in older adults. Importantly, these findings challenge commonly held worries about cognitive decline in older adults receiving ECT. It should be a regular consideration for management of this challenging illness in a population that may otherwise not respond to pharmacotherapy.

Muscarinic Cholinergic Receptor Agonist and Peripheral Antagonist for Schizophrenia

BackgroundThe muscarinic receptor agonist xanomeline has antipsychotic properties and is devoid of dopamine receptor–blocking activity but causes cholinergic adverse events. Trospium is a peripherally restricted muscarinic receptor antagonist that reduces peripheral cholinergic effects of xanomeline. The efficacy and safety of combined xanomeline and trospium in patients with schizophrenia are unknown.MethodsIn this double-blind, phase 2 trial, we randomly assigned patients with schizophrenia in a 1:1 ratio to receive twice-daily xanomeline–trospium (increased to a maximum of 125 mg of xanomeline and 30 mg of trospium per dose) or placebo for 5 weeks. The primary end point was the change from baseline to week 5 in the total score on the Positive and Negative Syndrome Scale (PANSS; range, 30 to 210, with higher scores indicating more severe symptoms of schizophrenia). Secondary end points were the change in the PANSS positive symptom subscore, the score on the Clinical Global Impression–Severity (CGI-S) scale (range, 1 to 7, with higher scores indicating greater severity of illness), the change in the PANSS negative symptom subscore, the change in the PANSS Marder negative symptom subscore, and the percentage of patients with a response according to a CGI-S score of 1 or 2.ResultsA total of 182 patients were enrolled, with 90 assigned to receive xanomeline–trospium and 92 to receive placebo. The PANSS total score at baseline was 97.7 in the xanomeline–trospium group and 96.6 in the placebo group. The change from baseline to week 5 was −17.4 points with xanomeline–trospium and −5.9 points with placebo (least-squares mean difference, −11.6 points; 95% confidence interval, −16.1 to −7.1; P<0.001). The results for the secondary end points were significantly better in the xanomeline–trospium group than in the placebo group, with the exception of the percentage of patients with a CGI-S response. The most common adverse events in the xanomeline–trospium group were constipation, nausea, dry mouth, dyspepsia, and vomiting. The incidences of somnolence, weight gain, restlessness, and extrapyramidal symptoms were similar in the two groups.ConclusionsIn a 5-week trial, xanomeline–trospium resulted in a greater decrease in the PANSS total score than placebo but was associated with cholinergic and anticholinergic adverse events. Larger and longer trials are required to determine the efficacy and safety of xanomeline–trospium in patients with schizophrenia. (Funded by Karuna Therapeutics and the Wellcome Trust; ClinicalTrials.gov number, NCT03697252.)

Efficacy of intensive orbitofrontal continuous Theta Burst Stimulation (iOFcTBS) in Obsessive Compulsive Disorder: A Randomized Placebo Controlled Study

Transcranial magnetic stimulation (TMS) can non-invasively modulate specific brain regions in Obsessive-compulsive disorder (OCD). Citing orbito-frontal cortex (OFC) hyper-connectivity with striatum as the most consistent finding implicated in patho-physiologically of OCD, we aimed to study the effect of novel continuous Theta Burst Stimulation (cTBS) targeting OFC in OCD subjects on a randomized placebo control design. Thirty-three patients were randomly allocated to active cTBS (n= 18) and sham (n= 15) groups. They received 10 TBS sessions, 2 per day (total of 1200 pulses; intensive protocol) for 5 days in a week. The Yale Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impression-Severity (CGI-S) scores were assessed at baseline, after last session and at 2 weeks post-rTMS. On repeated measures-ANOVA, a significant group*time effect (from pretreatment to 2 weeks post TBS) for obsessions, compulsions, HAM-A, HAM-D, and CGI scores was found. But when controlled for confounding variables, only HAM-A scores and CGI effect retained statistical significance. We conclude that intensive OFC cTBS (iOFcTBS) in OCD is well tolerated with clinically significant improvements in anxiety symptoms and global severity. This improvement in anxiety symptoms could be due to modulations of state dependent dysregulation in OCD.

Clinically meaningful changes on depressive symptom measures and patient-reported outcomes in patients with treatment-resistant depression.

ObjectiveTo use the Clinical Global Impression‐Severity (CGI‐S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery‐Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire‐9 (PHQ‐9) in patients with treatment‐resistant depression (TRD).MethodsPooled data were derived from two 4‐week, randomized, active‐controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI‐S, MADRS, SDS, and PHQ‐9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ‐9 that corresponded to a clinically meaningful (1‐point) or clinically substantial (2‐point) change on the CGI‐S scale were identified.ResultsClinically meaningful changes in CGI‐S scores after 28 days corresponded to 6‐, 4‐, and 3‐point changes from baseline on the MADRS, SDS, and PHQ‐9, respectively. Similarly, a 2‐point CGI‐S score change (clinically substantial change) corresponded to a 12‐, 8‐, and 6‐point change on the MADRS, SDS, and PHQ‐9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ‐9).ConclusionWe provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.

Defining "Adequately Treated": A Post Hoc Analysis Examining Characteristics of Patients with Schizophrenia Successfully Transitioned from Once-Monthly Paliperidone Palmitate to Once-Every-3-Months Paliperidone Palmitate.

PurposePaliperidone palmitate once every 3 months (PP3M) is indicated in adults with schizophrenia adequately treated with once-monthly paliperidone palmitate (PP1M) for at least 4 months, in whom the last two consecutive doses are the same. The decision of when to transition to PP3M is based on the patient’s symptom status while receiving PP1M.Patients and MethodsIn a double-blind relapse–prevention study (NCT01529515), patients who met Positive and Negative Syndrome Scale (PANSS) score stabilization criteria after 4 months of PP1M were eligible for transition to PP3M; those who continued to meet stabilization criteria after 12 weeks following an open-label PP3M dose were randomized to receive PP3M or placebo. We compared (post hoc) PANSS, Clinical Global Impression–Severity (CGI-S), and Personal and Social Performance (PSP) scores during the pre-randomization, open-label phase in patients in randomized versus non-randomized groups using analysis of variance or chi-square tests.ResultsOf 506 patients enrolled, 305 were randomized. After 4 months’ PP1M treatment, PANSS and CGI-S scores were significantly lower and PSP scores significantly higher in randomized patients versus non-randomized patients (least squares means [95% CI]: 57.1 [55.7, 58.6] vs 62.2 [60.0, 64.3], 2.9 [2.8, 3.1] vs 3.3 [3.1, 3.4], and 67.0 [65.7, 68.3] vs 64.5 [62.6, 66.4], respectively); changes from baseline between groups differed significantly (all P ≤0.009).ConclusionConfirming adequate stabilization with PP1M prior to transitioning to PP3M is critical in maximizing treatment response; clinicians should consider transitioning patients to PP3M only if patients respond well to PP1M for at least 4 months and their last two consecutive doses are the same.

Low-Dose Ziprasidone in Combination with Sertraline for First-Episode Drug-Naïve Patients with Schizophrenia: A Randomized Controlled Trial

Background: Many patients with SCZ discontinue antipsychotics, frequently due to dose related multiple and severe adverse effects. This clinical trial was designed to investigate the efficacy, safety, and tolerability of adding sertraline to ziprasidone in order to substantially reduce its dose and potential side effects in first-episode and drug-naive (FEDN) patients with SCZ. Methods: This 24-week randomized, double-blinded controlled clinical trial randomly allocated 452 FEDN SCZ patients to receive a usual dose of ziprasidone (control group) or half the dose of ziprasidone in combination with sertraline (ZS group). Treatment outcome included the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Rating Scale (HAMD), CGI-Severity (CGI-S) and the Personal and Social Performance Scale (PSP) at baseline and weeks 2, 4, 8, 12 and 24. Findings: Repeated measures ANCOVA showed significant treatment by time interactions on the PANSS negative symptom, general psychopathology and total scores, as well as CGI-S, HAMD and PSP scores (all p<0.05). Furthermore, the ZS group had greater reductions in PANSS negative symptoms, general psychopathology and total scores (all p<0.05) and greater increases in the PSP total score (p<0.01) than the control group. Importantly, adverse effects were lower in the ZS than control group. The reduction in PANSS, CGI-S or HAMD scores was not correlated with the increase in PSP. Sex and duration of disease predicted PSP improvement from baseline to week 24 in the ZS group. Interpretation: Our FEND patients with SCZ were effectively treated for their psychotic and depressive symptoms while experiencing significantly fewer adverse effects using half the usual ziprasidone dose when combined with sertraline. The implications for long term improved retention and compliance with treatment using this combination therapy are substantial for introducing them to life saving chronic care that will be optimally effective and minimally aversive due to antipsychotic side effects including cardiac problems. Trial Registration: The clinical trial was registered with ClinicalTrials.gov (ClinicalTrials.gov Identifier NCT04076371). Funding: Funding for this study was provided by the CAS Pioneer Hundred Talents Program. Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the Institutional Review Board of First Hospital of Shanxi Medical University

Impact of clozapine on disability and course of illness in patients with schizophrenia: A study from North India.

Aim:The aim of this study was to evaluate the impact of long-term use of clozapine on disability and course of illness among patients with treatment-resistant schizophrenia.Materials and Methods:102 participants who have been receiving clozapine for a mean duration of 5 years were evaluated on Positive and Negative Syndrome Scale (PANSS) rating, Clinical Global Impression (CGI) severity rating, and Indian Disability Evaluation and Assessment Scale (IDEAS) and the scores were compared with the scores on the same scales at the time of starting clozapine.Results:There was a significant reduction in both CGI-severity scores and scores in all the four domains of IDEAS, alongside a significant reduction on all three subscales of PANSS with clozapine treatment. The CGI global improvement subscale was rated as very much improved for 80 patients. In terms of course of symptoms, at 6 months of clozapine use, three-fourth of the patients were rated as having partial recovery with no relapse of symptoms, but with passage of time, the proportion of patients in the category of “complete recovery” was found to be increasing. Higher CGI severity at the follow-up, lower CGI global improvement, and poorer efficacy index were associated with higher disability at the follow-up.Conclusions:The present study suggests that clozapine has a significant beneficial impact on disability and course of illness among patients with treatment-resistant schizophrenia.

What are the predictors of CGI- severity in chronic schizophrenia patients

Introduction. The CGI-S score is an essential tool used in the evaluation of the severity of schizophrenia symptoms. It provides an objective and standardized measure of symptom severity that can be used to monitor treatment response and guide clinical decision-making. The CGI-S score alone may not provide sufficient information regarding the underlying factors contributing to the patient’s clinical presentation. Additionally, exploring the correlation between CGI-S score and other variables, such as sociodemographic and medical history factors, treatment history and other scales (PANNS, GAF, LUNSERS, SWN) can help clinicians better understand the factors that contribute to symptom severity and identify strategies to optimize treatment outcomes for patients with schizophrenia. Method. This study was conducted between 01.10.2009 – 01.10.2012, at the Clinical Hospital of Psychiatry Al. Obregia, Bucharest, Romania, on 110 patients, each of whom received a CGI-severity score at 7-day intervals. Excluding the small number of patients with a CGI-S score of 6 (6 out of 110), the study results are presented for 104 patients, divided into three categories based on the CGI-Severity score, respectively CGI-S 3,4, and 5. Descriptive analysis was performed on the subjects, and the ANOVA Tukey analysis was utilized to determine any significant correlation between the CGI-S score and other factors that could impact it. Results. We included 104 patients in our study, of whom 18.3% (n=19), 51.9% (n=54), and 29.8% (n=31) had a CGI-Severity score of 3, 4, and 5 points, respectively. Among them, 59.6% were female (n=62) and 40.4% were male (n=42), with a mean age of 40.19 (SD 10.35). We could not identify a statistically significant association between the CGI-S score and sociodemographic or medical history factors. However, we observed a significant negative association between the CGI-S score and the GAF and PANSS scales, with a p&lt;0.006. We also found a significant association between CGI-S score and the level of medication procurement accessibility, with a p-value of 0.039 and a 95% CI (-1.65 to 0.04) between CGI-S scores of 3 and 4. Among other predictive factors for the CGI-S score, we identified the presence of adverse effects measured using the LUNSERS scale (in terms of extrapyramidal and psychic adverse effects) and a significant association between the CGI-S score and the Subjective Well-Being Under Neuroleptics scale (in terms of physical function, self-control, and social integration; SWN), with a p&lt;0.05. Conclusion. It is important to correlate the CGI-S scale in schizophrenia with other scales such as PANSS, GAF, SWN, LUNSERS, illness history, and the patient’s treatment history because this provides a more comprehensive understanding of the patient’s symptoms, level of functioning, and response to treatment. By using multiple scales and considering various aspects of the patient’s illness, clinicians can make more informed decisions about the most appropriate treatment approach and monitor the patient’s progress over time. This can ultimately lead to better outcomes for patients with schizophrenia.

Relationship between clinical outcomes measures and personal and social performance functioning in a prospective, interventional study in schizophrenia

ObjectivesTo explore clinical and demographic characteristics impacting patient functioning by determining extent of overlap in factors driving change in Personal and Social Performance (PSP) and other clinical outcomes.MethodsPost‐hoc analysis from a single‐arm trial of paliperidone extended release in adult patients with nonacute symptomatic schizophrenia. Psychosocial functioning measures: PSP, Clinical Global Impression–Severity (CGI‐S), Positive and Negative Syndrome Scale (PANSS), Short‐Form 36 (SF‐36), treatment satisfaction, sleep quality/daytime drowsiness, and Extrapyramidal Symptoms Rating Scale.ResultsHighest correlations with PSP total score change included PANSS total score change (Spearman's r = 0.607), PANSS general psychopathology change (r = 0.579), and CGI‐S change (r = 0.569). A PSP score change of −32 predicted 90% probability of deterioration in CGI‐S (score change of ≥1). The power of PSP change to predict PANSS total score change was lower. Linear stepwise regression demonstrated independent relationships for PSP change and: PANSS total change; CGI‐S change; SF‐36 Mental Component change; treatment satisfaction at endpoint; PSP at baseline; previous psychiatric hospitalizations. R 2 = 0.55 meant that 45% of PSP variation could not be explained by other clinical outcome measures.ConclusionsPsychosocial functioning improvement is important in schizophrenia. PSP may be valuable for assessing functioning; it encompasses psychosocial and clinical factors not measured by other established assessments.

Defining tic severity and tic impairment in Tourette Disorder

ObjectiveTreatment guidelines for Tourette's Disorder (TD) are based on patients' degree of tic severity and impairment. However, clear benchmarks for determining tic severity and impairment have not been established. This study examined benchmarks of tic severity and tic impairment using the Yale Global Tic Severity Scale (YGTSS) and the Clinical Global Impression of Severity (CGI-S). MethodIndividuals with TD or another Tic Disorder (N = 519) recruited across nine sites were administered a diagnostic interview, the YGTSS, and the CGI-S. Correlations and trend analyses contrasted YGTSS scores across CGI-S ratings. A logistic regression model examined predictive benchmarks for tic severity, tic impairment, and global severity. Model classifications were compared against CGI-S ratings, and agreement was examined using kappa. ResultsSpearman correlations between the CGI-S and YGTSS scores ranged from 0.54 to 0.63 (p < 0.001). Greater CGI-S ratings were associated with a linear stepwise increase in YGTSS Total Tic scores, Impairment scores, and Global Severity scores. Despite moderate-to-strong associations (ρ = 0.45–0.56, p < 0.001) between the CGI-S and predictive logistical regression models, only fair agreement was achieved when applying classification benchmarks (κ = 0.21–0.32, p < 0.001). ConclusionsCGI-S ratings are useful to characterize benchmarks for tic severity, tic impairment, and global severity on the YGTSS. Logistic regression model benchmarks had only fair agreement with the CGI-S and underscore the heterogeneity of TD symptoms. Collectively, findings offer guidance on the delineation of tic severity categorizations to apply evidence-based treatment recommendations.

Obsessive compulsive symptoms severity among children and adolescents during COVID-19 first wave in Israel‏

Several current publications have considered persons with obsessive compulsive disorder (OCD) as particularly vulnerable during the COVID-19 period, and to require more frequent symptom monitoring. The purpose of this study was to evaluate whether OCD exacerbated during the first wave of COVID-19 in children and adolescents. Twenty-nine children and adolescents with OCD were evaluated in the midst of the first outbreak of the COVID-19 pandemic in Israel (April–May 2020). Obsessive-compulsive symptoms (OCS) were assessed using the Clinical Global Impression Scale (CGI), by means of a functional questionnaire and by the Obsessive-Compulsive Inventory-child version (OCI-CV) questionnaires. Obsessive-compulsive symptoms were not found to have exacerbated during the period investigated, as evident by a lack of change in CGI severity scores and by improvement rather than deterioration among more participants, based on the CGI improvement scores. Additionally, the children and adolescents reported better general functioning during the COVID-19 period and had relatively low scores on the OCI-CV scale. Our findings indicate that Israeli children and adolescents with OCD coped well with COVID-19 during the first two months of the pandemic and mostly did not experience exacerbation of OCS. However, due to the short duration of exposure to the pandemic at the time of the study, social isolation and lockdown might have masked OCS; thus, further longitudinal studies are needed.

Evaluating functional disability in clinical trials of lisdexamfetamine dimesylate in binge eating disorder using the Sheehan Disability Scale

ObjectivesThis study examined Sheehan Disability Scale (SDS) performance in binge eating disorder (BED) and explored relationships between SDS and BED outcomes using data from three placebo‐controlled lisdexamfetamine (LDX) studies (two short‐term, dose‐optimized studies and one double‐blind, randomized‐withdrawal study) in adults with Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM‐IV‐TR)–defined BED.MethodsAnalyses evaluated the psychometric properties of the SDS.ResultsConfirmatory factor analysis supported a unidimensional total score in the short‐term studies, with internal consistency (Cronbach's α) being 0.878. Total score exhibited good construct validity, with moderate and statistically significant correlations observed with Yale–Brown Obsessive Compulsive Scale modified for binge eating, Binge Eating Scale (BES), and EuroQol Group 5‐Dimension 5‐Level health status index scores. Known‐groups validity analysis for the short‐term studies demonstrated a significantly lower total score at end of study in participants considered “not ill” versus “ill” based on Clinical Global Impressions–Severity scores. SDS total score changes in the short‐term studies were greater in responders than nonresponders based on binge eating abstinence or BES score. In the randomized‐withdrawal study, SDS scores increased relative to baseline to a greater extent in participants randomized to placebo than LDX.ConclusionsThese analyses support the reliability, validity, and responsiveness to change of the SDS in individuals with BED.

Exacerbation of obsessive compulsive disorder symptoms in children and adolescents during COVID-19 pandemic

ObjectiveTo investigate the effects of COVID-19 pandemic and related home confinement on symptom profile, symptom severity and exacerbation of obsessive compulsive disorder (OCD) symptoms and related factors among young subjects with OCD. MethodYoung subjects who have been followed up with a primary diagnosis of OCD in a university hospital were reached by telephone or online programs to assess symptom profile, symptom severity and exacerbation during pandemic. Children's Yale-Brown Obsessive Compulsive (CY-BOCS) and Clinical Global Impression- Severity (CGI-S) Scales were used to rate symptom profile and severity before pandemic and during pandemic periods. ResultsThere was a significant increase in the frequency of contamination obsessions (p=0.008) and cleaning/washing compulsions (p=0.039) during pandemic period. CY-BOCS obsessions (p<0.001), compulsions subscales (p<0.001) and total scores (p<0.001), and CGI-S scores (p<0.001) during pandemic period were statistically higher than before pandemic period. There was a significant relationship between the change in CY-BOCS scores with talking/searching in the social environment about COVID-19, daily preoccupation about COVID-19, duration of OCD diagnosis and diagnosis of COVID-19 in someone familiar. ConclusionsYoung subjects with OCD may develop additional symptoms and worsen already existing symptoms of OCD during COVID-19 pandemic.

A Phase III, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of Once-daily SPN-812 (Viloxazine Extended-release) in the Treatment of Attention-deficit/Hyperactivity Disorder in School-age Children

PurposeThe limitations of current US Food and Drug Administration (FDA)–approved medications for the treatment of attention-deficit/hyperactivity disorder (ADHD) set the need for the development of novel, effective, and tolerable medications to treat this disorder. The purpose of this study was to evaluate whether treatment with SPN-812 (viloxazine extended-release) significantly reduces symptoms of ADHD in children. MethodsThis study was a randomized, double-blind, placebo-controlled 6-week trial to assess the efficacy and safety of once-daily 100- and 200-mg SPN-812 in the treatment of ADHD in male and female children 6–11 years of age. Inclusion criteria required subjects to have a confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, ADHD diagnosis, an ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and for subjects to be free of ADHD medication ≥1 week before randomization. The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 Total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS and CFB at EOS in the Conners 3–Parent Short Form (Conners 3–PS) Composite T-score and the Weiss Functional Impairment Rating Scale–Parent (WFIRS–P) Total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical examinations, ECGs, and the Columbia-Suicide Severity Rating Scale. The primary efficacy endpoint was analyzed by using a mixed model for repeated measures; all secondary measures were analyzed by using an ANCOVA model. ResultsA total of 477 subjects were randomized to treatment (intent-to-treat population, n = 460). The majority of subjects were male (63%) and either White (51.3%) or African American (43.7%). The demographic and baseline characteristics between the groups were similar. Statistically significant improvements in ADHD-RS-5 Total score were observed in both the 100- and 200-mg/day SPN-812 treatment groups compared to placebo at week 1 of treatment (P = 0.0004 and P = 0.0244, respectively), which was maintained through EOS (P = 0.0004 and P < 0.0001). Significant improvements were also observed at EOS in the CGI-I scale (P = 0.0020 and P < 0.0001), Conners 3–PS Composite T-score (P = 0.0003 and P = 0.0002), and WFIRS–P Total average score (P = 0.0019 and P = 0.0002) versus placebo. Treatment-related AEs reported in ≥5% of subjects included somnolence, decreased appetite, and headache. The discontinuation rate due to AEs was <5%. ImplicationsSPN-812 significantly reduced ADHD symptoms in children and was well tolerated. SPN-812 may prove to be an effective treatment for children with ADHD. ClinicalTrials.gov identifier: NCT03247530.