Clinical Global Impression-Severity Scale Research Articles

Intravenous trazodone for the treatment of psychomotor agitation and associated symptoms in major depressive disorder patients experiencing a depressive episode with mixed features.

Psychomotor agitation is a challenging symptom of major depressive disorder with mixed features (MDD-MF), often worsening outcomes and complicating treatment. This retrospective study assessed the efficacy and tolerability of intravenous trazodone in 97 hospitalized patients with MDE-MF. Symptom severity was evaluated using montgomery asberg depression rating Scale (MADRS), young mania rating scale, hamilton anxiety rating scale, GAD-7, and clinical global impression scale-severity of illness (CGI-S) scales, with significant reductions in agitation, anxiety, and irritability observed early during treatment. Correlation analyses revealed significant negative associations between intravenous (IV) trazodone dosage and improvements in MADRS (r = -0.23; P < 0.05), item 5 of GAD-7 (r = -0.27; P < 0.001), and CGI-S scores (r = -0.22; P < 0.05). Therapy duration also correlated negatively with improvements in GAD-7 item 5 (r = -0.29; P < 0.001) and CGI-S (r = -0.27; P < 0.001), indicating diminishing returns with prolonged treatment. Regression analyses showed that therapy duration, but not dosage, significantly influenced improvements in GAD-7 item 5 and CGI-S. Trazodone was well-tolerated, with only mild side effects in 11.3% of patients. These findings suggest that IV trazodone effectively reduces agitation and related symptoms in MDD-MF, particularly in the early treatment phase, emphasizing the importance of optimizing treatment duration. Future studies should investigate individualized dosing strategies and explore long-term outcomes in this population.

Study of Clinical Profile and Short-term Outcome of Dissociative Disorder in Children and Adolescents—An Observational Study

Introduction: Dissociative disorder is a common and distressing condition seen in children and adolescents, especially in the Indian population. It is associated with impairment in routine functioning, school absenteeism, and a significant distress and economic burden on the caregivers. There is scarcity of outcome studies in the Indian population. Aims: This study aimed to evaluate the sociodemographic and clinical profile of children and adolescents with dissociative disorder and find the outcome with treatment as usual at the end of one month. Methods: This was an observational study conducted in a tertiary care hospital over a period of one year. Fifty-one children and adolescents with mean age 14.2 years (± 2.050) with dissociative disorder (International Classification of Diseases, 10th revision [ICD-10]) were included in the study. Sociodemographic and clinical details were assessed using semi-structured proforma and Children Global Assessment Scale (CGAS), and Clinical Global Impression-Severity (CGI-S) were used to assess baseline functioning. After one month of treatment, as usual, outcome was assessed either face-to-face or through telecommunication using CGAS, CGI-S scales. Results: Dissociative stupor (37.3%) was the most common type of presentation followed by dissociative convulsions (21.6%). Most prevalent stressor was familial (39.2%) and parenting style was authoritative (19.6%). Slow-to-warm-up temperament was most frequent (39.2%) in study subjects. At the end of one month of treatment as usual on CGAS, the percentage of subjects with obvious or serious problems reduced to 7.9 from 35.3% which was statistically significant ( P &lt;.05). On CGI-S 56.8% of the participants significantly improved on follow-up ( P &lt; .05). On CGI-I, 51% had much improvement, 19.1% showed very much improvement from baseline, whereas, 31.4% had minimal improvement. Conclusion: Dissociative disorders are common in adolescent age and most commonly associated with familial stressors and authoritative parenting in our study. We found a significant number improved at the end of one month with treatment as usual indicating good short-term outcomes.

Use of Electroconvulsive Therapy Treatment in Adolescents in Singapore.

Electroconvulsive therapy (ECT) is a highly effective treatment for schizophrenia and mood disorders; however, most evidence is derived from the adult population, with less evidence in adolescents. We sought to determine the use of ECT in adolescents in the Institute of Mental Health (IMH) and evaluate the treatment outcome. We conducted a retrospective naturalistic analysis of ECT registry data of patients aged from 10 to 19 years from March 2017 to March 2023. Descriptive analysis was used to analyze the demographics and clinical characteristics. Paired t tests were used to compare the change in clinical outcome scores, including the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impressions Scale - Severity (CGI-S), and Montreal Cognitive Assessment (MoCA) before and after 2 weeks of ECT treatment. Fifty-five patients were included for analysis. There was a significant improvement in BPRS (P < 0.001), MADRS (P = 0.005), and CGI-S (P < 0.001), and the average CGI-I score was 2.275 (SD, 0.81), which is equivalent to "much improved" after 6 sessions of treatment. Of all patients, 48.5% showed significant clinical improvement. There was no significant change in MoCA scores (P = 0.218). Our preliminary findings show that ECT is a safe, rapid, and effective treatment for psychotic and mood disorders in adolescents. Further studies with a larger sample size and specific subgroup analysis are needed to establish the effectiveness of ECT and identify predictors of response in this population.

Effects of immune modulatory treatment on language and psychiatric profile in patients with electrical status epilepticus in sleep (ESES).

Electrical status epilepticus in sleep (ESES) is an electrographic pattern associated with cognitive impairment. Our study aimed to prospectively evaluate the psychiatric findings and language skills in patients diagnosed with ESES and to determine the immune modulatory treatment-responsive subgroups. We assessed the patients for psychiatric features and language skills at the baseline and 12months after. Psychiatric disorders were screened according to DSM-V criteria. We implemented standardized tests including Clinical Global Impressions-Severity Scale (CGI-S), Revised-Children Anxiety and Depression Scale, Children's Sleep Habits Questionnaire-Abbreviated, Aberrant Behavior Checklist (ABC), and Childhood Autism Rating Scale. We used tests adapted/developed for Turkish language including Test of Language Development-Primary-Fourth Edition: Turkish (TOLDP-4:T), Turkish Non-word Repetition Test (TNRT), Turkish Multilingual Sentence Repetition Test (MultiSIT-TR) and Turkish Communication Development Inventory (TCDI). Disability was evaluated by Pediatric Evaluation of Disability Inventory (PEDI). Thirty-nine patients were included. Psychiatric evaluation revealed attention deficit hyperactivity disorder-like symptoms in 25 patients, intellectual disability in 12, and specific learning disability in 8. Patients were treated with corticosteroids or IVIg in addition to anti-seizure medication. The spike wave indexes improved significantly at the end of follow-up period (80% (65-91) vs. 37% (24-65), p<0.001). After 12months, statistically significant improvement was found in ABC, CGI-S, TOLDP-4:T, TNRT, MultiSIT-TR, TCDI, and PEDI scores (p<0.05). Patients with improvement in psychiatric symptoms had earlier age. Phonologic working memory performance was significantly preserved and improved compared to other language domains. Immune modulatory treatments may contribute to improvement of psychiatric symptoms and language skills. Preservation of phonologic working memory and grammar performance might be a valuable feature to differentiate ESES-related language impairment.

Treatment with combined exercise in patients with resistant major depression (TRACE-RMD): study protocol for a randomised controlled trial

BackgroundAround 40% of people with major depressive disorder (MDD) experience moderate remission, with the remainder meeting the criteria for resistant major depression (RMD). It has been shown that exercise has a low-to-moderate effect on MDD, but there is a lack of evidence on exercise interventions in RMD patients. The primary purpose of the proposed study will be to investigate the effect of a 12-week supervised combined exercise program on depressive symptoms in people with RMD compared to a treatment-as-usual (TAU) group.MethodThis randomised, single-blind, controlled experimental trial will include 70 adults (≥ 18 years old) with RMD. Participants randomised to an exercise intervention, or a TAU group will be assessed at baseline and after a three-month intervention period. The primary variable will be participants’ depressive symptoms measured with the Montgomery-Asberg Depression Rating Scale. Secondary outcome variables will include cardiorespiratory fitness (peak oxygen uptake through peak cardiopulmonary exercise test), body composition (bioimpedance and anthropometric variables), physical activity level (the International Physical Activity Questionnaire), health-related quality of life (the Short Form-36 Health Survey), functional outcome (the Sheehan Disability Scale and Quality of Life in Depression Scale), overall disease severity (the Clinical Global Impression Scale-Severity of Illness), and biochemical variables (a fasting blood sample).DiscussionThis study will try to answer whether a supervised co-adjuvant combined (aerobic and resistance training) exercise program will help the prognosis of this population with RMD.Trial registrationClinicalTrials.gov NCT05136027. Last public release on 12/13/2023.

Effectiveness of Buspirone in Alleviating Anxiety Symptoms in Patients with Depressive Disorder: A Multicenter Prospective Observational Study in Korea.

We aimed to investigate the effectiveness of buspirone as an adjunctive therapy for alleviating anxiety symptoms in patients with depressive disorders who are already taking antidepressants. This was an open-label prospective multicenter non-interventional observational study conducted over 12 weeks. We enrolled 180 patients diagnosed with depressive disorders according to DSM-5 criteria and Hamilton Anxiety Rating Scale (HAMA) scores ≥ 18. Participants were already taking selective serotonin reuptake inhibitors or serotoninnorepinephrine reuptake inhibitors and were prescribed adjunctive buspirone. Efficacy was assessed using HAMA, Hamilton Depression Rating Scale (HAMD), Clinical Global Impression Scale-Improvement, Clinical Global Impression Scale-Severity, Sheehan Disability Scale (SDS), and WHO-5 Well-Being Index. The efficacy analysis included 161 patients. HAMA scores decreased significantly from 25.2 ± 6.7 at baseline to 15.4 ± 8.6 at 12 weeks (p < 0.001), whereas HAMD scores decreased from 19.4 ± 4.6 to 12.7 ± 5.7 (p < 0.001). WHO-5 and SDS scores showed significant improvements. The HAMA response rate was 39.1% and the remission rate was 13.7% at 12 weeks. Adverse drug reactions were reported in 3.7% of participants. Subgroup analyses showed no significant differences in treatment response based on buspirone dosage, baseline anxiety/depression severity, or benzodiazepine use. Adjunctive buspirone therapy effectively improved anxiety symptoms in depressed patients taking antidepressants, regardless of baseline symptom severity or buspirone dosage. The treatment was well-tolerated with few adverse events. Future studies using a control group are needed.

Maintenance Intramuscular Ketamine-Assisted Psychotherapy, a Retrospective Chart Review of Efficacy, Adverse Events, and Dropouts from a Community Practice

ABSTRACT The use of ketamine and ketamine-assisted psychotherapy (KAP) for treatment of depression has grown dramatically, though much of these data are short term. The clinical profile of maintenance treatment remains poorly characterized. We assessed maintenance KAP for efficacy, tolerability, and reasons for dropout. This observational study retrospectively analyzed electronic health records from an addiction psychiatry practice offering intramuscular ketamine with contemporaneous psychotherapy for the treatment of depression. All patients receiving treatment between January 2016 and September 2022 were included, yielding 1,114 sessions from 70 patients. The response was quantified via the clinical global impression-severity scale. Side effects and reasons for dropout were extracted from charts. Comorbidities include an anxiety disorder (79%) or substance use disorder (49%). The induction yielded 82% response, maintained above 80% after six months (sessions q21 days, 1.13 mg/kg mean dose). Many (38%) remained in treatment for at least one year. Nausea management accounted for nearly all as-needed medication use. Antihypertensives were seldom utilized. Chronic side effects were notable for one case of ketamine use disorder, resulting in residential treatment. Dropouts cited logistical reasons half the time and side effects only 9.7% of the time. KAP yielded robust improvements in mood, anxiety, and substance use. Maintenance sessions effectively extended benefit and were largely well tolerated.

Comparisons between obsessive-compulsive disorder and trichotillomania in terms of autistic traits and repetitive behaviors in adolescents

Background Our study aims to reveal the relationship between autistic traits and repetitive behaviors in adolescents diagnosed with obsessive-compulsive disorder and trichotillomania and to compare them to healthy controls. Method A total of 100 adolescents, 33 of whom were diagnosed with obsessive-compulsive disorder, 32 of whom were diagnosed with trichotillomania and 35 healthy controls, aged 11-18 years, who applied to a Child and Adolescent Psychiatry Outpatient Clinic between February 2023 and July 2023, were included in the study. Participants were evaluated with the Autism Spectrum Quotient (AQ)-Adolescent, Repetitive Behavior Scale-Revised (RBS-R), Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and Clinical Global Impression Scale-Severity (CGI-S). SPSS 25.0 program was used in the analysis. p < 0.05 was accepted as the significance level. Results It was found that adolescents diagnosed with obsessive-compulsive disorder and trichotillomania had higher autistic trait levels compared to healthy controls, while there was no significant difference between the obsessive-compulsive disorder and trichotillomania groups. While stereotypic, routine, sameness, and restricted repetitive behaviors were more common in the obsessive-compulsive disorder and trichotillomania groups as opposed to healthy controls, it was found that compulsive behavior was more common in the obsessive-compulsive disorder group, and self-injurious behavior was more common in the trichotillomania group compared to healthy controls. Conclusion The findings of our study indicate that adolescents diagnosed with trichotillomania, similar to those with obsessive-compulsive disorder, have a higher level of autistic traits and repetitive behaviors. The authors believe it is crucial to focus on the social skill difficulties these adolescents may be experiencing.

Comparing two transitioning strategies to paliperidone palmitate once-every-6-months.

A double-blind, randomized, active-controlled, parallel-group, noninferiority trial (NCT03345342) demonstrated that paliperidone palmitate once-every-6-months (PP6M) was noninferior to paliperidone palmitate once-every-3-months (PP3M) in preventing relapse in clinically stable adults with schizophrenia. This post hoc analysis assessed efficacy and safety following transition to PP6M from paliperidone once-monthly (PP1M) versus PP3M. Adults with schizophrenia who were clinically stable on moderate/high doses of PP1M or PP3M were randomly assigned 1:2 to dorsogluteal PP3M or PP6M treatment for 12months. The primary efficacy measure was time to relapse during the 12-month DB phase. Secondary endpoints included change from DB baseline to endpoint in Positive and Negative Syndrome Scale (PANSS) total and subscale scores, Clinical Global Impression-Severity (CGI-S) scale score, and Personal and Social Performance (PSP) scale score. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory tests. Of 702 patients in the study, 231 transitioned from PP1M to PP6M and 247 transitioned from PP3M to PP6M. Low relapse rates for PP6M were observed regardless of transition pathway (PP1M/PP6M: 7.8%; PP3M/PP6M: 7.3%). Changes from DB baseline to endpoint in PANSS total, PSP, and CGI-S scores were similar between transition groups. In the DB phase, ≥1 TEAE was observed in 61.0% and 63.2% of patients in the PP1M/PP6M and PP3M/PP6M, groups, respectively. Adults with schizophrenia who transitioned to PP6M from either PP1M or PP3M experienced similarly low relapse rates. Additionally, symptom and functionality scores supported the primary analysis and, along with TEAE incidences, were comparable between transition groups.

Association of Cannabis Use Reduction With Improved Functional Outcomes: An Exploratory Aggregated Analysis From Seven Cannabis Use Disorder Treatment Trials to Extract Data-Driven Cannabis Reduction Metrics.

This exploratory analysis sought to determine whether decreases in cannabis use are associated with improvements in cannabis-related problems and functional outcomes, and if so, what percentage decrease is associated with improvement. Data were aggregated from seven cannabis use disorder treatment trials conducted in the United States (N=920; ages 13 years and older; mean age, 25 years; 30% female, 7% Black, 11% Hispanic/Latinx). Outcome measures included the patient-reported Marijuana Problems Scale (MPS), Health-Related Quality of Life scale (HRQOL), and Pittsburgh Sleep Quality Index and the clinician-rated Clinical Global Impressions (CGI) severity and improvement scales (CGI-S and CGI-I). Generalized estimating equations tested the association between changes in 4-week cannabis use and improvements in functional outcomes. Classification and regression tree (CART) models were developed to determine what reductions in cannabis use could be used as classifiers of improvement. Decreases in the amount and frequency of cannabis use were significantly associated with improvements in MPS severity and total scores as well as improvements on the CGI-I and in sleep quality, but not improvements on the HRQOL. CART models performed best for CGI-I scores (72%-75% correct classification), while other outcome measures did not perform as well (40%-62% correct classification). CART models showed improvements on the CGI at 74% reduction in use amounts and 47% reduction in use days. Reductions in cannabis use (∼50% reduction in use days and ∼75% reduction in use amounts) were associated with clinician-assessed improvement, which suggests that cannabis use reduction may yield benefit among individuals with cannabis use disorder. These exploratory results extract a data-driven metric to inform future studies, clinicians, patients, and policy recommendations.

Efficacy of Clonidine Adhesive Patch for Patients With Tourette Syndrome: A Randomized, Double-blind, Placebo-Controlled, Multicenter Clinical Trial.

This study aimed to explore the efficacy of the clonidine adhesive patch for participants with Tourette syndrome (TS). This randomized, double-blind, placebo-controlled, multicenter phase IV clinical trial included participants with TS at 20 centers between May 2012 and March 2015. Treatment efficacy at week 8 was the primary outcome. The Clinical Global Impression-Severity scale and Improvement scale were the secondary endpoints. This trial included 488 participants, with 121 participants in the 2.0-mg/wk group, 119 participants in the 1.5-mg/wk group, 126 participants in the 1.0-mg/wk group, and 122 participants in the placebo group. For Yale Global Tic Severity Scale score reduction rate, compared with the placebo group (39.60 ± 25.56), those of the 2.0-mg/wk group (63.21 ± 32.60) and the 1.5-mg/wk group (68.16 ± 25.88) were statistically significantly different (all P < 0.001). For total Yale Global Tic Severity Scale score, compared with the placebo group (17.0 ± 8.03), the score for the 2.0-mg/wk group was 9.9 ± 8.36 ( P < 0.001); 1.5-mg/wk group, 9.6 ± 8.03 ( P < 0.001); and 1.0-mg/wk group, 10.5 ± 9.28 ( P < 0.001). The Clinical Global Impression-Severity scale and Improvement scale scores were statistically significantly different in the 3 clonidine (or experimental) groups compared with the placebo group (all P < 0.001). Larger doses of the clonidine adhesive patch such as 1.5 and 2.0 mg/wk are effective in improving the symptoms and overall function of participants with TS.

Evaluating the Efficacy of a Digital Therapeutic (CT-152) as an Adjunct to Antidepressant Treatment in Adults With Major Depressive Disorder: Protocol for the MIRAI Remote Study.

Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. This study aimed to describe a phase 3 remote, multicenter, randomized, masked, sham-controlled trial evaluating the efficacy of a smartphone app-based DTx (CT-152) in adult participants diagnosed with MDD, used as an adjunct to antidepressant therapy (ADT). Participants aged 22-64 years with a current primary diagnosis of MDD and an inadequate response to ADT were included. Participants were randomized 1:1 to CT-152 or a sham DTx. CT-152 is a smartphone app-based DTx that delivers a cognitive-emotional and behavioral therapeutic intervention. The core components of CT-152 are the Emotional Faces Memory Task exercises, brief lessons to learn and apply key therapeutic skills, and SMS text messaging to reinforce lessons and encourage engagement with the app. The sham DTx is a digital working memory exercise with emotionally neutral stimuli designed to match CT-152 for time and attention. Participants took part in the trial for up to 13 weeks. The trial included a screening period of up to 3 weeks, a treatment period of 6 weeks, and an extension period of 4 weeks to assess the durability of the effect. Sites and participants had the option of an in-person or remote screening visit; the remaining trial visits were remote. Efficacy was evaluated using the Montgomery-Åsberg Depression Rating Scale, the Generalized Anxiety Disorder-7, Clinical Global Impression-Severity scale, the Patient Health Questionnaire-9, and the World Health Organization Disability Assessment Schedule 2.0. The durability of the effect was evaluated with the Montgomery-Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7 scale. Adverse events were also assessed. Satisfaction, measured by the Participant and Healthcare Professional Satisfaction Scales, and health status, measured by the EQ-5D-5L, were summarized using descriptive statistics. This study was initiated in February 2021 and had a primary completion date in October 2022. This represents the methodological design for the first evaluation of CT-152 as an adjunct to ADT. This study protocol is methodologically robust and incorporates many aspects of conventional pivotal pharmaceutical phase 3 trial design, such as randomization and safety end points. Novel considerations included the use of a sham comparator, masking considerations for visible app content, and outcome measures relevant to DTx. The rigor of this methodology will provide a more comprehensive understanding of the effectiveness of CT-152. ClinicalTrials.gov NCT04770285; https://clinicaltrials.gov/study/NCT04770285. RR1-10.2196/56960.

Serum Thiols and Ischemia-Modified Albumin Levels in Children With Major Depressive Disorder: A Cross-Sectional Study.

Introduction This cross-sectional study aimed to investigate potential biomarkers of oxidative stress by analyzing serum thiol-disulfide homeostasis (TDH) and ischemia-modified albumin (IMA) levels in children who have been diagnosed with major depressive disorder (MDD). Methods The study included 24 medication-naive children aged seven to 17 years diagnosed with MDD and 19 healthy controls matched for age, gender, and body mass index. Clinical interviews were conducted using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL-DSM-5), and diagnoses were made according to DSM-5. The Child Depression Inventory (CDI) and the Clinical Global Impression Scale-Severity (CGI-S) were also administered to the participants. Venous blood samples were taken from all subjects to assess TDH and IMA levels, considered potential oxidative stress indicators. Results The study showed no significant difference in TDH and IMA levels between the MDD and the control groups. Although not statistically significant, it was observed that native thiol and total thiol levels were higher in the MDD group. No direct relationship was found between disease severity and either TDH or IMA levels. Conclusion In conclusion, while there were no significant differences in the levels of TDH and IMA, higher levels of both native and total thiols were found in the MDD group.

A hybrid model for predicting response to risperidone after first episode of psychosis.

Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of first episode of psychosis (FEP). patients to the antipsychotic risperidone. We evaluated 141 antipsychotic-naïve FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale were considered responders (n = 72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical+genetic factors) with and without feature selection were created. Clinical models presented greater balanced accuracy 63.3% (confidence interval [CI] 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76] - kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84] - RF algorithm). A hybrid model, including clinical and genetic predictors, can provide enhanced predictions of response to antipsychotic treatment.

Prevalence and clinical correlates of abnormal lipid metabolism in older Chinese patients with first-episode drug-naïve major depressive disorder

BackgroundOlder major depressive disorder (MDD) patients have more complex clinical symptoms and higher abnormal lipid metabolism (ALM) rates. This study aimed to compare clinical differences between those with and without ALM in a sample of older first-episode drug naïve (FEDN) patients.MethodsWe recruited 266 older MDD patients. Socio-demographic variables, clinical data, and lipid parameters were obtained. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS-P) were conducted to evaluate patients’ depression, anxiety and psychotic symptoms, respectively.ResultsIn this study, we found that the prevalence of comorbid ALM was 86.1% in older MDD patients. Compared with the non-abnormal lipid metabolism (NALM) group, the ALM group had a higher duration of illness, higher clinical global impression of severity scale (CGI-S) and HAMD scores, higher thyroid stimulating hormone (TSH) and glucose levels. Logistic regression analysis indicated that duration of illness (OR = 1.11, P = 0.023, 95%CI = 1.015–1.216) and CGI-S score (OR = 2.28, P = 0.014, 95%CI = 1.18–4.39) were associated with ALM in older MDD patients.ConclusionThe importance of regular lipid assessment in older MDD patients needs to be taken into account.

Long-term safety and effectiveness of lurasidone in adolescents and young adults with schizophrenia: pooled post hoc analyses of two 12-month extension studies

Background and ObjectivesThe aim of this analysis was to evaluate the long-term safety and effectiveness of lurasidone in the treatment of schizophrenia in adolescents and young adults (13–25).MethodsThe 2 pooled studies used similar designs and outcome measures. Patients (13–25) with schizophrenia completed an initial double-blind 6-week trial of lurasidone (40 and 80 mg/day) in the adolescent trial and (80 and 160 mg/day) in the young adult trial. In open-label long-term trials, adolescent patients were treated with 20–80 mg/day lurasidone, and adults were treated with 40–160 mg/day lurasidone. Efficacy was evaluated based on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity Scale (CGI-S).ResultsThe safety population consisted of 306 patients (mean age, 16.2 years; 208 patients (68.0%) who completed 12 months of treatment; 8.2% who discontinued treatment by 12 months due to an adverse event). The mean (SD) changes in the PANSS total score from the extension baseline to months 6 and 12 were − 11.8 (13.9) and – 15.3 (15.0), respectively (OC), and the mean (SD) changes in the CGI-S score were − 0.8 (1.0) and − 1.0 (1.1), respectively (OC). The most frequent adverse events were headache (17.6%), anxiety (11.4%), schizophrenia (9.8%), and nausea (9.8%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn adolescents and young adults with schizophrenia, treatment with lurasidone was generally well tolerated and effective. Long-term treatment was associated with a continued reduction in symptoms of schizophrenia. Long-term treatment was associated with minimal effects on weight, metabolic parameters, and prolactin.Clinicaltrials.gov identifiers D1050234, D1050302.

Three-Year Outcomes of 6-Month Paliperidone Palmitate in Adults With Schizophrenia

Long-acting injectable (LAI) antipsychotics have the potential to improve adherence and symptom control in patients with schizophrenia, promoting long-term recovery. Paliperidone palmitate (PP) once every 6 months is the first and currently only LAI antipsychotic with an extended dosing interval of 6 months. To assess long-term outcomes of PP received once every 6 months in adults with schizophrenia. In a 2-year open-label extension (OLE) study of a 1-year randomized clinical trial (RCT), eligible adults with schizophrenia could choose to continue PP every 6 months if they had not experienced relapse after receiving PP once every 3 or 6 months in the 1-year, international, multicenter, double-blind, randomized noninferiority trial. The present analysis focused on patients receiving PP every 6 months in the double-blind trial through the OLE study (November 20, 2017, to May 3, 2022). Patients received a dorsogluteal injection of PP on day 1 and once every 6 months up to month 30. End points included assessment of relapse and change from the double-blind trial baseline to the OLE end point in Positive and Negative Syndrome Scale (PANSS) total and subscale, Clinical Global Impression-Severity (CGI-S) Scale, and Personal Social Performance (PSP) Scale scores. Treatment-emergent adverse events (TEAEs), injection site evaluations, and laboratory tests were also assessed. Among 121 patients (83 [68.6%] male), mean (SD) age at baseline was 38.6 (11.24) years and mean (SD) duration of illness was 11.0 (9.45) years. At screening of the double-blind study, 101 patients (83.5%) were taking an oral antipsychotic and 20 (16.5%) were taking an LAI antipsychotic. Altogether, 5 of 121 patients (4.1%) experienced relapse during the 3-year follow-up; reasons for relapse were psychiatric hospitalization (2 [1.7%]), suicidal or homicidal ideation (2 [1.7%]), and deliberate self-injury (1 [0.8%]). Patients treated with PP every 6 months were clinically and functionally stable, and outcomes were well maintained, evidenced by stable scores on the PANSS (mean [SD] change, -2.6 [9.96] points), CGI-S (mean [SD] change, -0.2 [0.57] points), and PSP (mean [SD] change, 3.1 [9.14] points) scales over the 3-year period. In total, 101 patients (83.5%) completed the 2-year OLE. At least 1 TEAE was reported in 97 of 121 patients (80.2%) overall; no new safety or tolerability concerns were identified. In a 2-year OLE study of a 1-year RCT, results supported favorable long-term outcomes of PP once every 6 months for up to 3 years in adults with schizophrenia.

The Clinical Characteristics and Manifestation of Anxious Depression Among Patients With Major Depressive Disorders-Results From a Taiwan Multicenter Study.

Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD. We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D). In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression-Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics. Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.

Efficacy of a synbiotic in the management of adults with Attention-Deficit and Hyperactivity Disorder and/or Borderline Personality Disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, “basket” trial

Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18–65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (−3.6, 95 % CI:-6.8 to −0.3; P = 0.03), emotional symptoms (−0.6, 95 % CI:-1.2 to −0.05; P = 0.03), inattention (−1.8, 95 % CI: −3.2 to −0.4; P = 0.01), functioning (−2.7, 95 % CI: −5.2 to −0.2; P = 0.03) and perceived stress levels (−0.6, 95 % CI: −1.2 to −0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: −4.3 to – 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. Trial RegistrationClinicalTrials.gov Identifier: NCT03495375.

Prevalence and factors associated with dyslipidemia in patients with first hospitalization for major depressive disorder: a large sample cross-sectional study.

Major depressive disorder (MDD) is a severe mental illness with high relapse rates and high mortality. Depression not only severely limits psychosocial functioning but also reduces quality of life. It can also negatively affect patients' clinical parameters, including lipid metabolism markers. This study aimed to investigate the prevalence and risk factors of hyperlipidemia (HL) in patients with MDD who were hospitalized for the first time. In this study, we enrolled 981 patients with MDD who were hospitalized for the first time, collected their demographic data and biochemical indicators, and evaluated their clinical symptoms. We divided the patients into HL and non-HL subgroups based on whether they had co-morbid HL. We compared whether there were significant differences between the two groups regarding demographics and general clinical information. A total of 708 of 981 MDD patients were described as being in the hyperlipidemic group, with an incidence of 72.17%. Clinical Global Impression Scale-Severity of Illness (CGI-SI) score and Hamilton Depression Scale (HAMD) score are risk factors for co-morbid HL in patients with MDD. The area under the ROC curve for the CGI-SI and HAMD score and their combined discriminatory ability was approximately 63%, 67%, and 68%, respectively. The prevalence of HL was high in patients with MDD who were first hospitalized; Higher HAMD score and CGI-SI score were risk factors for the development of HL in MDD; The HAMD score and the CGI-SI score are predictive of the severity of HL.