Clinical Global Impression Research Articles

The Effectiveness and Safety Analysis of Duloxetine in Treating Comorbid Depression in Parkinson's Disease: A Retrospective Study.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and non-motor symptoms, including depression, which significantly impacts the quality of life of affected individuals. This study aims to investigate the real-world effectiveness and safety of duloxetine in treating comorbid depression in patients with Parkinson's disease and to compare its outcomes with traditional treatment approaches. This study included adult patients diagnosed with Parkinson's disease combined with depression from December 2020 to December 2023. Based on the use of duloxetine, the cohort was divided into a traditional treatment group and a duloxetine group (traditional treatment combined with duloxetine). Patients with incomplete medical records, concurrent antidepressant therapy, or major psychiatric or neurological disorders were excluded. Retrospective data, including demographic information, treatment adherence, and various assessment scores, were collected from medical records by trained research staff. In total, 106 patients were analyzed, with 50 patients receiving traditional treatment and 56 patients receiving duloxetine. The duloxetine group exhibited significantly lower scores than the traditional treatment group in the Unified PD Rating Scale (p = 0.015), Hamilton Depression Rating Scale (p = 0.013), Beck Depression Inventory (p = 0.031), Parkinson's disease Questionnaire-39 (p = 0.006), and Clinical Global Impression-Improvement (p < 0.001) scores. In motor function assessment, the duloxetine group demonstrated improvements in kinetic tremor scores (p = 0.017), gait speed (p < 0.001), Timed Up and Go Test performance (p < 0.001), dyskinesia severity (p = 0.017), and rigidity (p = 0.019) compared to the traditional treatment group. Additionally, the duloxetine group exhibited better cognitive function across various assessments, including the Symbol Digit Modalities Test (p = 0.024), Stroop Color-Word Test (p = 0.048), and Montreal Cognitive Assessment (p = 0.024). Duloxetine is associated with superior efficacy in improving motor and non-motor symptoms, overall clinical status, and cognitive function. These findings support the potential utility of duloxetine as a comprehensive treatment option for comorbid depression in Parkinson's disease.

Structural Equation Modeling of Childhood Trauma and Self-Stigma in Adult Inpatients with Borderline Personality Disorder.

Child abuse and trauma are significant risk factors in the etiology of borderline personality disorder (BPD). Apart from affecting the risk of developing BPD, adverse childhood experiences seem to increase its symptoms and related disability. Self-stigma presents another common issue with equally prominent consequences for mental health. Despite being theoretically linked, the connections among childhood trauma, self-stigma, and mental health have not been explored in patients with BPD. This study aimed to provide first insights into this understudied topic. This cross-sectional study included 283 inpatients diagnosed with BPD participating in a residential transdiagnostic psychotherapeutic program. The patients completed several measurements - the Internalized Stigma of Mental Illness Scale, the Childhood Trauma Questionnaire - Short Form, the Clinical Global Impression - Severity, the Beck Depression Inventory-II, the Beck Anxiety Inventory, the Dissociative Experiences Scale, the Sheehan Disability Scale, and a demographic questionnaire. The data was statistically analyzed using IBM SPSS and AMOS 26 programs, and bivariate correlation tests and structural equation modeling explored the hypotheses. Retrospectively reported childhood trauma positively correlated with current self-stigma. Both childhood trauma and self-stigma were also positively related to several indicators of general psychopathology and disability. The significance of these connections was subsequently confirmed by structural equation modeling, where self-stigma acted as a partial mediator of childhood trauma, general psychopathology, and disability. Self-stigma significantly mediates the relationship between childhood trauma and selected mental health symptoms among adult patients diagnosed with BPD. Longitudinal studies are necessary to explore the causality of the findings. Therapeutic and societal efforts to tackle childhood trauma or self-stigma might benefit from reflecting its broader psychosocial context.

Exploring correlations between Conners' Continuous Performance Test and subjective measures of attention deficit hyperactivity disorder symptoms in a paediatric clinical sample.

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental condition characterised by inattention and/or hyperactivity-impulsivity. The ADHD symptoms are often evaluated and quantified using various assessment tools, such as the Conners' Continuous Performance Test II (CCPT-II), ADHD Rating Scale (ADHD-RS), Child Behaviour Checklist (CBCL), Clinical Global Assessment Scale (CGAS) and Clinical Global Impression Scale (CGIS). This study sought to compare CCPT-II with parent- and clinician-rated rating scales (ADHD-RS, CBCL, CGAS and CGIS) in measuring the core ADHD symptoms within the paediatric ADHD population. The data, gathered from a large-scale randomised controlled trial involving 172 children aged 6-12 years with ADHD, was pooled, and a Pearson correlation analysis was conducted. No significant correlations were observed between CCPT-II and ADHD-RS, as well as the various subscales of CBCL, CGAS and CGIS. While CCPT-II may offer insights into ADHD symptomatology, its relationship with parent- and clinician-rated rating scales such as ADHD-RS, CBCL, CGAS and CGIS appears limited. Further research is warranted to elucidate the nuances of these assessment tools and their roles in evaluating ADHD.

Development and Validation of SCACOMS, a Composite Scale for Assessing Disease Progression and Treatment Effects in Spinocerebellar Ataxia.

Spinocerebellar ataxias (SCA) are rare inherited neurodegenerative disorders characterized by a progressive impairment of gait, balance, limb coordination, and speech. There is currently no composite scale that includes multiple aspects of the SCA experience to assess disease progression and treatment effects. Applying the method of partial least squares (PLS) regression, we developed the Spinocerebellar Ataxia Composite Scale (SCACOMS) from two SCA natural history datasets (NCT01060371, NCT02440763). PLS regression selected items based on their ability to detect clinical decline, with optimized weights based on the item's degree of progression. Following model validation, SCACOMS was leveraged to examine disease progression and treatment effects in a 48-week SCA clinical trial cohort (NCT03701399). Items from the Clinical Global Impression-Global Improvement Scale (CGI-I), the Friedreich Ataxia Rating Scale (FARS) - functional stage, and the Modified Functional Scale for the Assessment and Rating of Ataxia (f-SARA) were objectively selected with weightings based on their sensitivity to clinical decline. The resulting SCACOMS exhibited improved sensitivity to disease progression and greater treatment effects (compared to the original scales from which they were derived) in a 48-week clinical trial of a novel therapeutic agent. The trial analyses also provided a SCACOMS-derived estimate of the temporal delay in SCA disease progression. SCACOMS is a useful composite measure, effectively capturing disease progression and highlighting treatment effects in patients with SCA. SCACOMS will be a powerful tool in future studies given its sensitivity to clinical decline and ability to detect a meaningful clinical impact of disease-modifying treatments.

Single-blinded, randomised, parallel-group, controlled trial comparing the efficacy and cost-effectiveness of therapist- and self-guided internet-delivered behavioural activation versus treatment as usual for adolescents with mild to moderate depression: study protocol

IntroductionThe number of adolescents seeking professional help for depression is increasing and, despite advances in treatment, large unmet treatment needs remain. In the current protocol, we describe the design and...

Impact of air pollution exposure on the severity of major depressive disorder: Results from the DeprAir study.

Major depressive disorder (MDD) is one of the most prevalent medical conditions worldwide. Different factors were found to play a role in its etiology, including environmental ones (e.g., air pollution). The aim of this study was to evaluate the association between air pollution exposure and MDD severity. Four hundred sixteen MDD subjects were recruited. Severity of MDD and functioning were evaluated through five rating scales: Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HAMD), Clinical Global Impression (CGI), Global Assessment of Functioning (GAF), and Sheehan Disability Scale (SDS). Daily mean estimates of particulate matter with diameter ≤10 (PM10) and 2.5 μm (PM2.5), nitrogen dioxide (NO2), and apparent temperature (AT) were estimated based on subjects' residential addresses. Daily estimates of the 2 weeks preceding recruitment were averaged to obtain cumulative exposure. Multivariate linear and ordinal regression models were applied to assess the associations between air pollutants and MDD severity, overall and stratifying by hypersusceptibility and AT. Two-thirds of subjects were women and one-third had a family history of depression. Most women had depression with symptoms of anxiety, while men had predominantly melancholic depression. NO2 exposure was associated with worsening of MDD severity (HAMD: β = 1.94, 95% confidence interval [CI], [0.41-3.47]; GAF: β = -1.93, 95% CI [-3.89 to 0.02]), especially when temperatures were low or among hypersusceptible subjects. PM exposure showed an association with MDD severity only in these subgroups. Exposure to air pollution worsens MDD severity, with hypersusceptibility and lower temperatures being exacerbating factors.

The minimal important difference in obsessive-compulsive disorder: An analysis of double-blind SSRI trials in adults.

The change in symptoms necessary to be clinically relevant in obsessive-compulsive disorder (OCD) is currently unknown. In this study, we aimed to create an empirically validated threshold for clinical significance or minimal important difference (MID). We analyzed individual participant data from short-term, double-blind, placebo-controlled registration trials of selective serotonin reuptake inhibitors in adult OCD patients. Data were collected from baseline to week 12. We used equipercentile linking to equate changes in the Clinical Global Impression (CGI) scale to changes in the Yale-Brown Obsessive-Compulsive Scale (YBOCS). We defined the MID as the YBOCS change linked to a CGI improvement of 3 (defined as "minimal improvement"). We included 7 trials with a total of 1216 patients. The CGI-scores and YBOCS were moderately to highly correlated. The MID corresponded to 4.9 YBOCS points (95% CI 4.4-5.4) for the full sample, or a 24% YBOCS-decrease compared to baseline. The MID varied with baseline severity, being lower in the group with mild symptoms and higher in the group with severe symptoms. By linking the YBOCS to the CGI-I, this is the first study to propose an MID in OCD trials. Having a clearly defined MID can guide future clinical research and help interpretation of efficacy of existing interventions. Our results are clinician-based; however, there is further need for patient-reported outcomes as anchor to the YBOCS.

Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: results from an open-label phase Ib ascending dose study.

Short-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgiasthat feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency. Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes. No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re-configured relationships to their headache pain. The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment.

Measuring clinically relevant change in apathy symptoms in ADMET and ADMET 2.

Among participants with Alzheimer's disease (AD) we estimated the minimal clinically important difference (MCID) in apathy symptom severity on three scales. Retrospective anchor- and distribution-based analyses of change in apathy symptom scores. Apathy in Dementia Methylphenidate Trial (ADMET) and ADMET 2 randomized controlled trials conducted at three and ten clinics specialized in dementia care in United States and Canada, respectively. Two hundred and sixty participants (60 ADMET, 200 ADMET 2) with clinically significant apathy in Alzheimer's disease. The Clinical Global Impression of Change in Apathy scale was used as the anchor measure and the MCID on the Neuropsychiatric Inventory - Apathy (NPI-A), Dementia Apathy Interview and Rating (DAIR), and Apathy Evaluation Scale-Informant (AES-I) were estimated with linear mixed models across all study visits. The estimated thresholds were evaluated with performance metrics. Among the MCID was a decrease of four points (95% CI: -4.0 to -4.8) on the NPI-A, 0.56 points (95% CI: -0.47 to -0.65) on the DAIR, and three points on the AES-I (95% CI: -0.9 to -5.4). Distribution-based analyses were largely consistent with the anchor-based analyses. The MCID across the three measures showed ∼60% accuracy. Sensitivity analyses found that MMSE scores and apathy severity at baseline influenced the estimated MCID. MCIDs for apathy on three scales will help evaluate treatment efficacy at the individual level. However, the modest correspondence between MCID and clinical impression of change suggests the need to consider other scales.

The effect of the EXOPULSE Mollii Suit on pain and fibromyalgia-related symptoms-A randomized sham-controlled crossover trial.

Fibromyalgia pain and related symptoms are poorly managed by approved pharmacological and alternative interventions. This trial aimed to evaluate the effects of the EXOPULSE Mollii Suit-a multisite transcutaneous electrical nerve stimulation device-on fibromyalgia pain, fatigue, affective symptoms, disease impact, and quality of life. Adult patients with fibromyalgia were enrolled. Phase 1 implied a randomized, sham-controlled, cross-over, double-blind trial, applying daily 1 h sessions of active or sham intervention, over 2 weeks (2-week washout). In the open-label phase 2, all patients received daily active intervention for 4 weeks. Comparisons on pain, fatigue, disease impact, affective symptoms, quality of life, clinical impression, and comfort ratings were performed using Friedman, Wilcoxon signed rank, and Chi2 tests. Thirty-three patients completed the study (93.9% female, mean age: 51.3 years). Pain (primary endpoint assessed via a visual analog scale) was significantly reduced after the active (pre-active: 6.9 ± 1.4, post-active: 5.9 ± 1.8, pre-sham: 6.8 ± 1.4, post-sham: 6.6 ± 1.5) versus the sham intervention (X2 = 10.60, p = 0.014). This was also the case of other secondary endpoints (i.e., fatigue, anxiety, and disease impact), except depression and quality of life. The Clinical Global Impression of Change (CGI-C) was significantly different between the active and sham intervention periods (X2 p = 0.035), and the different proportions of categories were as follows: 'worsening' (sham: 18.2% vs. active: 0.0%), 'improvement' (sham: 48.5% vs. active 63.6%) or 'no change (sham: 33.3% vs. active 36.4%) respectively. After phase 2, significant positive effects were observed for most of the outcomes, and 78.8% of patients reported improvement according to CGI-C. This study suggests the clinical benefits of the EXOPULSE Mollii Suit in alleviating pain and fibromyalgia-related fatigue, emotional symptoms, and disease impact. It is worth noting that the study has several limitations related to the low number of participants, the short-term analysis of effects in the first blinded and controlled phase, and the open-label nature of phase 2. Future studies with a larger cohort and longer protocol treatment are needed, to further confirm the current results, and evaluate the long-term effects of this technique. Patients with fibromyalgia suffer from pain as well as fatigue, sleep impairment, emotional disturbances, and altered quality of life. Transcutaneous electrical nerve stimulation might help manage those symptoms, but the available systems are limited by the fact that they could be applied at best over two sites. This randomized controlled study is the first to apply a multi-site transcutaneous electrical nerve stimulation device, the EXOPULSE Mollii Suit, with significant effects on fibromyalgia pain and related symptoms.

Efficacy of once-nightly sodium oxybate (FT218) on daytime symptoms in individuals with narcolepsy with or without concomitant alerting agent use: A post hoc analysis from the phase 3 REST-ON trial

Objective/BackgroundExtended-release, once-nightly sodium oxybate (ON-SXB) significantly improved narcolepsy symptoms in participants in the phase 3, randomized, double-blind, placebo-controlled REST-ON trial. This post hoc analysis of REST-ON data evaluated ON-SXB efficacy in participants with or without concomitant alerting agent use. Patients/methodsParticipants with narcolepsy aged >16 years were randomized 1:1 to ON-SXB (week 1: 4.5 g, weeks 2–3: 6 g, weeks 4–8: 7.5 g, weeks 9–13: 9 g) or placebo. Primary endpoints in this post hoc analysis included change from baseline in mean sleep latency on the Maintenance of Wakefulness Test (MWT), Clinical Global Impression-Improvement (CGI-I) rating, and number of weekly cataplexy episodes. The secondary endpoints were change from baseline in the Epworth Sleepiness Scale (ESS) score and in objective and subjective disrupted nighttime sleep parameters. Post hoc analyses assessed participants with and without alerting agent use across 6-, 7.5-, and 9-g doses. ResultsIn the modified intent-to-treat population, 119 (63 %) were (ON-SXB, n = 66; placebo, n = 53) and 71 (37 %) were not (ON-SXB, n = 31; placebo, n = 40) taking alerting agents. Regardless of alerting agent use, treatment with ON-SXB resulted in significant improvements vs placebo (all doses, P < 0.05) for MWT, CGI-I, and number of weekly cataplexy episodes. Significant improvements in ESS (all doses, P < 0.05) with ON-SXB vs placebo were observed in the alerting agent use cohort. Directional improvements in ESS were reported with all doses in the no alerting agent use group. ConclusionsRegardless of concomitant alerting agent use, ON-SXB improved daytime and nighttime narcolepsy symptoms vs placebo.

Effectiveness of Medhasagar Rasa® in Combating Aging-Associated Mild Neurocognitive Disorder: An Open-Label, Exploratory, Interventional Clinical Trial.

With the rising prevalence of neurocognitive disorders (NCDs) among the aging population, particularly in conditions like mild cognitive impairment (MCI), which often precedes dementia, there remains a significant gap in effective pharmacological interventions. This has generated interest in exploring alternative therapies to manage symptoms and enhance cognitive function in the aging population. The primary objective of this study was to evaluate the effect of Medhasagar Rasa® on cognitive functions, daily functioning, and quality of life in participants with aging-associated mild neurocognitive disorder using the Montreal Cognitive Assessment (MoCA) Scale, Ayurvedic Manasabhava Scale, and Brief Cognitive Rating Scale (BCRS). This open-label, interventional study at Karnatak Lingayat Education (KLE) Ayurveda Hospital, Belagavi, Karnataka, involved 32 screened participants, with 30 completing the study. Participants aged 50-70 years with MoCA scores of 18-25 received Medhasagar Rasa (2 tablets at bedtime, provided by M/s. Shree Dhootapapeshwar Limited, Mumbai, India) for 60 days. Assessments occurred at baseline and every 15 days until day 60. Thirty participants were recruited for the study after screening, all of whom completed the study. The median total MoCA score at baseline (visit one) was 20, which significantly improved to 25 by visit five (day 60±3) (p<0.001), indicating enhanced cognitive performance. The BCRS scores also showed significant improvement, with the median score decreasing from 12 to 7.5 (p<0.001) over 60 days. Anxiety symptoms were significantly reduced, with Hamilton Anxiety Rating Scale (HAM-A) scores dropping from 14 to 7 (p<0.001), while the Pittsburgh Sleep Quality Index (PSQI) scores indicated improved sleep quality, reducing from 9.5 to 7 (p<0.001). The Ayurvedic Manasabhava Scale also demonstrated a significant reduction in intensity (14 to 6; p<0.001) and frequency (13.5 to 6; p<0.001). Clinical Global Impression (CGI) scores showed stable illness severity, sustained global improvement, and consistent therapeutic efficacy. No adverse events were reported, and vital parameters remained normal throughout the study. Compliance with the medication was over 80%, and no significant changes were observed in laboratory values. Medhasagar Rasa effectively enhanced cognitive functions and alleviated anxiety and sleep disturbances in aging-related mild neurocognitive disorder, offering a promising therapeutic option.

Copper excess in psychiatric disorders: a focus on mood spectrum disorders and sex

BackgroundMeta-analyses show increased copper (Cu) levels in major depression disorder. However, the association of Cu biomarkers with clinical classification in other mental health disorders has not been fully explored. MethodsTo this aim, we compared an extensive panel of Cu biomarkers, composed of Cu, ceruloplasmin (Cp) Cp activity, Cp specific activity, Cu not bound to ceruloplasmin (non-Cp Cu, also known as ‘free’ copper) in 171 consecutive patients affected by psychiatric disorders and in 61 healthy controls (HC) using MANOVA adjusting for the effect of sex and age, and studied their association with the clinical scale outcomes at psychiatric examination, namely Global Assessment of Functioning, Clinical Global Impression, and Brief Psychiatric Rating Scale. Resultsindividuals with psychiatric disorders were classified as 109 patients affected by mood spectrum disorders (MSD), 20 patients with schizophrenia spectrum disorders (SSD), and 42 with personality disorders (PD). Cu and non-Cp Cu were increased in psychiatric individuals than in HC, which also differed among the patients stratified per the clinical classification, being higher in the MSD individuals. The analysis stratified for sex revealed that women from the patient group, and specifically from the MSD group, had increased levels of Cu and non-Cp Cu than healthy women, while no difference was revealed in men. A logistic regression model considering the effect of sex and age revealed that non-Cp Cu could explain 26 % increased odds of having MSD per µmol/L unit increase (OR = 1.26; p = 0.0008; 95 % CI 1.099–1.436), that reached 40 % when considering only women. This result was driven by non-Cp Cu that correctly classified 64.1 % MSD (70 % in women) individuals vs. HC in a decision tree model, with values higher than 2.1 µmol/L which could distinguish the majority of MSD patients (86.3 % MSD vs. 13.7 % HC in women). None of the biological variables under study correlated with outcomes of the clinical scales, substances, or alcohol abuse. ConclusionCurrent results suggest mild Cu toxicity in women with MSD, as revealed by a value of non-Cp Cu higher than 2.1 µmol/L, which can be further investigated to assess its potential diagnostic accuracy in bigger and longitudinal cohorts.

Investigation of optical coherence tomography angiography findings in patients with bipolar disorder

ObjectivesBipolar Disorder (BD) is an important psychiatric disease that progresses with attacks, can be chronic and causes serious mental problems. In this study, we aimed to identify the retinal vascular pathologies in BD patients by optical coherence tomography angiography (OCTA) imaging. MethodsRetinal vascular analysis from 35 BD patients and 30 healthy controls (HCs) were scanned using the OCTA machine. In addition, psychometric tests such as the Young Mania Rating Scale (YMRS) and Clinical Global Impression Scale (CGI-S) were applied to BD patients to assess the severity of the disease and determine the patient's level of functionality. ResultsAs a result of OCTA scans, there were significant differences between the groups as following; Deep retinal vessel density (VD) in the total, parafoveal and perifoveal area, Macular thickness in the inner parafoveal area, VD of retinal capillary plexuses in the inside disk and the Choroidal thickness (p < 0.05). Furthermore, according to the results of Pearson correlation analysis between OCTA scans and YMRS and CGI-S scores, it was determined that there was no significant relationship in any measurement (p > 0.05). ConclusionIn our study, it was determined that there were general differences in deep retinal vascular density and inner macular thickness in BD patients. These findings demonstrate that the deep and inner zone of the retina is affected in BD patients.

Long-Term Treatment for Unspecified Anxiety Disorders with Cannabidiol: A Retrospective Case Series from Real-World Evidence in Colombia

Introduction: Preclinical and clinical evidence has elucidated that cannabis-based medical formulations (CBMFs) may display anxiolytic, antidepressive, and neuroprotective properties. CBMFs are often considered as novel therapeutic anxiolytic agents that can be prescribed as pharmacotherapy for symptomatic domains in anxiety disorders (ADs). Our aim was to explore effectiveness and tolerability of enriched cannabidiol (CBD) oil extract formulations in adults with anxiety symptoms in an outpatient mental health program in Colombia during the COVID-19 pandemic. Methods: We conducted an observational, retrospective, real-world evidence case series from electronic health records at Zerenia Clinic in Bogotá, Colombia between June 2021 and December 2022. Our convenience sample consisted of people searching for CBMFs for the treatment of anxiety symptoms. A cohort of 24 adults was prescribed with enriched CBD in the form of non-sterile oral liquids suspended in sesame seed oil extracts for DSM-5 unspecified anxiety disorder and followed throughout the first year of treatment. CBMFs were prepared by dissolving full-spectrum cannabis extracts in sesame seed oil to a standardized concentration of active ingredients which is CBD-enriched. The oil extract contained 100 mg/mL of CBD and less than 1.9 mg/mL of THC. Primary outcome measures established were the anxiety subscale in the Hospital Anxiety and Depression Scale (HADS-A), and the clinical global impression scale with regard to severity (CGI-S) and improvement (CGI-I) at baseline, 6 months, and 12 months during follow-up. Secondary outcome measures established were HADS depression subscale (HADS-D) and the Epworth Sleepiness Scale (ESS), respectively. Participants also completed the patient-reported outcome measures (PROMs) during each visit throughout the 12-month follow-up. PROMs documented both participantʼs subjective improvement experience and progressive adverse effects. Results: After 6 months of treatment with sublingually administered enriched CBD oil extracts in a median dosage of 100 mg, more than half (54.17%) of the sample continued to report significant anxiety symptoms. After 12 months, only 37.50% persisted with significant anxiety symptoms with a median dose of 120 mg of enriched CBD oil extracts. Similar subjective improvements were reported with regard to sleep disturbances (SDs) as a secondary outcome. At baseline, less than half (46.83%) of the sample reported significant daytime sleepiness. After 6 months of enriched CBD oil extract treatment, less than one third (29.17%) continued to report SDs. At end point, a high proportion of the sample (87.50%) were considered to have normal daytime sleepiness. The cohort showed no clinically relevant depressive symptoms at baseline based on HADS-D scores; therefore, no improvement could be reported throughout the 12-month follow-up. Minimal gender differences with regard to HADS-D scores may be attributed to modifying effects of menopause-related symptoms. No significant adverse drug reactions or deaths were reported during the 12-month follow-up. Conclusions: Further research should determine the long-term efficacy, safety, and appropriate dosages of enriched CBD oil extracts in treating specific ADs rather than broad and unspecified anxiety symptoms. The state of the art of CBMFs for ADs should be warranted by future randomized controlled trials. The next stage for cannabis research should be focused in performing head-to-head trials comparing enriched CBD extracts or capsules versus first-line treatments proven to be effective in ADs.

Predictors of attrition during acute pharmacotherapy of psychotic depression in a clinical trial

Little is known about factors that contribute to attrition in clinical trials of the pharmacotherapy of psychotic depression. The purpose of this study was to identify factors associated with attrition during acute pharmacotherapy in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II) clinical trial. Sociodemographic and clinical variables were assessed at baseline in 269 men and women, aged 18–85 years, who were treated with up to 12 weeks of open-label sertraline plus olanzapine. Univariate analyses examined the association of baseline variables with overall non-completion, as well as reasons for non-completion. Logistic regression was used to model the relationship of the significant univariate predictors with non-completion and its reasons. Seventy-four (27.5 %) participants did not complete the acute treatment phase of STOP-PD II. Male gender, younger age, inpatient status, higher Clinical Global Impression (CGI) severity of illness, and higher severity of psychomotor disturbance were associated with non-completion in univariate analyses. In regression models, higher CGI severity of illness score was the only significant independent predictor of non-completion, explained by withdrawal of consent. Our findings have implications for the retention of persons with psychotic depression in clinical trials.

Acupuncture and Escitalopram for Treating Major Depression Clinical Study (AE-TMDCS): protocol for a factorial randomised controlled trial

IntroductionMajor depressive disorder (MDD), the second leading cause of disability globally, is considered to be associated with a consequent deterioration in the quality of life and can lead to a...

Longitudinal Symptom Burden and Pharmacologic Management of Catatonia in Autism with and without Profound Impairment: An Observational Study.

Catatonia is a highly morbid psychomotor and affective disorder which can affect autistic individuals with and without profound impairment. Catatonic symptoms are treatable with pharmacotherapy and electroconvulsive therapy, but the longitudinal effectiveness of these treatments has not been described. We conducted a prospective observational cohort study of patients with autism and co-morbid catatonia who received outpatient care in a specialized outpatient clinic from July 1st, 2021 to May 31st, 2024. Data investigating pharmacologic interventions, and clinical measures including the Bush Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), Kanner Catatonia Examination (KCE), and Clinical Global Impression - Improvement (CGI-I) were collected. Forty-five patients were identified with 39 (86.7%) meeting criteria for profound autism. All patients received pharmacotherapy. 44 (97.8%) were treated with benzodiazepines with a mean maximal daily dose of 17.4 mg (SD=15.8) lorazepam equivalents. Thirty-five patients (77.8%) required more than one medication class for treatment. Fourteen patients (31.1%) attempted to taper off benzodiazepines during the study period; of these, 5 patients (11.1%) were successfully tapered off, and the remaining 9 (17.8%) discontinued the taper due to a return of catatonic symptoms. Statistically significant improvement was observed across all clinical domains except the KCS. However, the majority remained symptomatic over the study period. Despite clinical improvements while receiving the gold standard for psychopharmacologic management of catatonia, chronic symptoms remained for the majority of catatonia patients over the study period, and few were able to taper and discontinue benzodiazepine treatment.

Assessment of the reliability, responsiveness, and meaningfulness of the scale for the assessment and rating of ataxia (SARA) for lysosomal storage disorders.

To evaluate the reliability, responsiveness, and validity of theScale for the Assessment and Rating of Ataxia (SARA) in patients with lysosomal storage disorders (LSDs) who present with neurological symptoms, and quantify the threshold for a clinically meaningful change. We analyzed data from three clinical trial cohorts (IB1001-201, IB1001-202, and IB1001-301) of patients with Niemann-Pick disease type C (NPC) and GM2 Gangliosidoses (Tay-Sachs and Sandhoff disease) comprising 122 patients and 703 visits. Reproducibility was described as re-test reliability between repeat baseline visits or baseline and post-treatment washout visits. Responsiveness was determined in relation to the Investigator's, Caregiver's, and Patient's Clinical Global Impression of Improvement (CGI-I). The CGI-I data was also used to quantify a threshold for a clinically meaningful improvement on the SARA scale. Using a qualitative methods approach, patient/caregiver interviews from the IB1001-301 trial were further used to assess a threshold of meaningful change as well as the breadth of neurological signs and symptoms captured and evaluated by the SARA scale. The Inter-Class Correlation (ICC) was 0.95 or greater for all three trials, indicating a high internal consistency/reliability. The mean change in SARA between repeat baseline and post-treatment washout visit assessments in all trials was -0.05, SD 1.98, i.e., minimal, indicating no significant differences, learning effects or other systematic biases. For the CGI-I responses and change in SARA scores, Area Under the Curve (AUC) values were 0.82, 0.71, and 0.77 for the Investigator's, Caregiver's, and Patient's CGI-I respectively, indicating strong agreement. Further qualitative analyses of the patient/caregiver interviews demonstrated a 1-point or greater change on SARA to be a clinically meaningful improvement which is directly relevant to the patient's everyday functioning and quality of life. Changes captured by the SARA were also paralleled by improvement in a broad range of neurological signs and symptoms and beyond cerebellar ataxia. Qualitative and quantitative data demonstrate the reliability and responsiveness of the SARA score as a valid measure of neurological signs and symptoms in LSDs with CNS involvement, such as NPC and GM2 Gangliosidoses. A 1-point change represents a clinically meaningful transition reflecting the gain or loss of complex function.

Positive psychological functioning, resilience and styles of coping as buffers against suicidal behaviours. A case-control study

BackgroundStudies in the literature mainly focus on understanding the risk factors for suicide, giving little relevance to protective variables. This study aimed at exploring the specific contribution of protective variables (resilience, coping and psychological well-being) in hospitalized suicide attempt (SA) makers. MethodsWe recruited 50 inpatients who made a SA before admission and 50 inpatients with no history of SA matched for DSM-5 diagnosis, gender and age. Protective variables were evaluated with: Brief COPE questionnaire, Dispositional Resilience Scale (DRS-15), Psychological Well-Being Scale (PWB-18). Psychopathological features and symptom severity were assessed with: Global Assessment of Functioning Scale (GAF), Rapid Dimensional Assessment Scale (SVARAD), Brief Psychiatric Rating Scale (BPRS), Clinical Global Impressions (CGI), Hamilton Depression Rating Scale (HDRS17). ResultsThe DRS-15 total score was significantly lower in SA makers. SA makers displayed significantly lower scores on the Engagement and Cognitive Restructuring subscales of the Brief COPE. On the PWB-18, the Self-Acceptance subscale score was lower in SA makers. LimitationsThe small sample size suggests the need for caution in interpreting the results. Matching was carried out by excluding diagnoses of personality disorders. ConclusionsPatients hospitalized following a SA are more often diagnosed with personality disorders, have deficit areas concerning resilience and coping, and lower psychological well-being compared to patients without a SA. When approaching a patient who has committed a SA, it may be useful to evaluate protective variables as well as risk factors, and encourage the development of adaptive coping mechanisms and positive self-evaluation through more dynamic therapeutic paths.