Clinical Global Impressions-Improvement Score Research Articles

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

FAT1 weighted MRI: Diffusion meets anatomical imaging and application in thalamic surgery for tremor

Abstract Patient-specific targeting of the Ventral intermediate nucleus (Vim) of the thalamus can be achieved with MR connectivity. Nevertheless, there are several drawbacks to using tractography-based targeting methods to visualise distinct thalamic nuclei (e.g., subjective region of interest selection, and thresholding of resulting tracts and clusters). Fractional anisotropy (FA) mapping, another product of diffusion MRI (dMRI), does not rely on tractography, and could thus be clinically more viable for discerning thalamic anatomy for stereotactic surgery. The aim of this study is to develop and present a hybrid, high-resolution, and high-fidelity imaging modality that combines contrast from FA maps as well as anatomical T1 sequences (FAT1 imaging); and to evaluate FAT1 based Vim-target definition. Imaging and outcome data of 35 consecutive refractory tremor patients who had undergone 43 connectivity guided deep brain stimulation (DBS) and/or radiofrequency thermocoagulation (RF-T) between 2013 and 2021 were included. First, the pre-operatively acquired dMRI and MPRAGE sequences were used to create FAT1 maps in retrospect. Then, an FAT1 based Vim-target was planned by an experienced functional neurosurgeon who was blinded for patient outcome. Finally, to investigate FAT1 based targeting, a post-hoc analysis was carried out of the degree of overlap between the newly created FAT1 based Vim-target, and the volume of tissue activation (VTA, in case of DBS) or lesion volume (in case of RF-T). This degree of overlap was compared between favourable and unfavourable outcome groups: outcomes were measured by experts blinded for imaging data at the last follow-up using a Clinical Global Impression-Improvement score (CGI-I), where a CGI-I score of 1-2 (i.e., FTMTRS improvement of ≥50%) was considered favourable. In 36 of the 43 (84%) performed surgeries (24 DBS and 19 RF-T), FAT1 based Vim-targeting was possible. For the group showing favourable outcome (71% of the patients at a median follow-up of 13 months), the mean amount of overlap between the FAT1 based Vim-target and the VTA or lesion was 42% (±13), versus 17% (±15) for patients with an unfavourable outcome (MD 25%, 95% CI 14–35, p < 0.0001). Retrospective use of FAT1 based Vim-targeting as a tool to predict outcome had a sensitivity of 90%, specificity of 80%, positive predictive value of 90%, and negative predictive value of 80%. In conclusion, FAT1 imaging is a new, high-resolution, and high-fidelity modality that combines diffusion and anatomical MRI. It provides a fast and efficacious way of targeting the ventral intermediate nucleus of the thalamus. In this study, FAT1 based targeting was highly accurate in predicting outcomes after deep brain stimulation and radiofrequency thalamotomy.

Structural Brain Connectivity and Treatment Improvement in Mood Disorder.

Background: The treatment of depressive episodes is well established, with clearly demonstrated effectiveness of antidepressants and psychotherapies. However, more than one-third of depressed patients do not respond to treatment. Identifying the brain structural basis of treatment-resistant depression could prevent useless pharmacological prescriptions, adverse events, and lost therapeutic opportunities. Methods: Using diffusion magnetic resonance imaging, we performed structural connectivity analyses on a cohort of 154 patients with mood disorder (MD) and 77 sex- and age-matched healthy control (HC) participants. To assess illness improvement, the patients with MD went through two clinical interviews at baseline and at 6-month follow-up and were classified based on the Clinical Global Impression-Improvement score into improved or not-improved (NI). First, the threshold-free network-based statistics (NBS) was conducted to measure the differences in regional network architecture. Second, nonparametric permutations tests were performed on topological metrics based on graph theory to examine differences in connectome organization. Results: The threshold-free NBS revealed impaired connections involving regions of the basal ganglia in patients with MD compared with HC. Significant increase of local efficiency and clustering coefficient was found in the lingual gyrus, insula, and amygdala in the MD group. Compared with the NI, the improved displayed significantly reduced network integration and segregation, predominately in the default-mode regions, including the precuneus, middle temporal lobe, and rostral anterior cingulate. Conclusions: This study highlights the involvement of regions belonging to the basal ganglia, the fronto-limbic network, and the default mode network, leading to a better understanding of MD disease and its unfavorable outcome.

Oxcarbazepine for the treatment of bipolar and depressive disorders in the outpatient setting: A retrospective chart review

Oxcarbazepine is often utilized off-label for bipolar and depressive disorders in outpatient settings despite limited evidence. We performed a retrospective chart review on 38 adult outpatients diagnosed with bipolar and depressive disorders (ICD-10 codes F30-39), treated with oxcarbazepine by psychiatrists and psychiatric nurse practitioners between 2015 and 2021. Primary outcomes were Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I) scores, assigned retrospectively from clinical documentation. Patients were predominantly female (70%), aged 20–76 (mean 36), with a mean of 1.8 DSM diagnoses (range 1–4) and 1.7 (range 0–5) concurrent psychotropic medications. A starting mean oxcarbazepine dose of 489 mg/day, titrated to a mean final dose of 663 mg/day, was associated with a CGI-I of 2.5 [2.25, 2.75] and a pre-to-post treatment decrease in CGI-S from 3.4 to 2.4. Overall response and remission rates were 52% and 29%, respectively. Limitations of this study include potential sample bias, documentation bias and rater bias among other limitations inherent to retrospective study designs.

Safety and efficacy of trofinetide in Rett syndrome: a systematic review and meta-analysis of randomized controlled trials

IntroductionRett syndrome is a rare genetic neurodevelopmental disorder that predominantly impacts females. It presents with loss of acquired skills, impaired communication, and stereotypic hand movements. Given the limited treatment options for Rett syndrome, there is a dire need for effective interventions.ObjectiveTo evaluate the safety and efficacy of trofinetide in Randomized Controlled Trials (RCTs) that report on Rett syndrome patients.MethodsWe identified 109 articles from four databases (Scopus, PubMed, Web of Science, and Cochrane CENTRAL). After removing the duplicates, we narrowed them down to 59 articles for further assessment. We included RCTs that evaluated the efficacy and safety of trofinetide in patients with Rett syndrome. Three studies were eligible for inclusion. Two independent reviewers evaluated the identified studies’ titles, abstracts, and full texts, extracting pertinent data. We assessed the quality of the studies using the Cochrane Risk of Bias (RoB) 2.0 tool. We then conducted a meta-analysis using the fixed effects model in the case of insignificant heterogeneity; otherwise, we used the random effects model. Based on the nature of the outcome, we analyzed the mean difference or the odds ratio. Analysis was conducted using RevMan version 5.3.ResultsAmong the analyzed outcomes in 181 patients in the trofinetide group and 134 patients in the placebo group, significant improvement in Rett Syndrome Behavior Questionnaire (RSBQ) scores was observed at 200 mg dosage (overall mean difference: -3.53, p = 0.001). Clinical Global Impression-Improvement (CGI-I) scores improved considerably at 200 mg dosage (overall mean difference: -0.34, p < 0.0001). No substantial changes were observed in Motor Behavioral Assessment (MBA) or Top 3 Caregiver Concerns. We evaluated Treatment Emergent Adverse Events (TEAEs) across the various dosages and noted significant associations with diarrhea (200 mg), vomiting (200 mg), and irritability (200 mg). However, we did not find a significant association between any of the dosages and the incidence of decreased appetite.ConclusionTrofinetide demonstrated potential in improving RSBQ and CGI-I scores at 200 mg dosage. Although no substantial changes were found in MBA and top 3 caregiver concerns. Adverse events were linked to specific dosages.

Time is ticking for TikTok tics: A retrospective follow-up study in the post-COVID-19 isolation era.

During the COVID-19 pandemic, an influx of adolescents presented worldwide with acute onset of functional tic-like behaviors (FTLBs). Our goal was to evaluate psychosocial factors around onset, to elucidate outcomes after pandemic isolation protocols were lifted, and to examine therapy and medication management. A retrospective review was performed of 56 patients ages 10-18 years with new-onset FTLBs seen at Boston Children's Hospital beginning in March 2020. Demographic factors, medical history, and treatment were evaluated. Patient outcomes were determined retrospectively based on the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales from follow-up visits. CGI-I scores assessed the progression of FTLBs; CGI-S assessed overall function. Ninety-six percent of patients were female-assigned at birth with high rates of comorbid anxiety (93%) and depression (71%). Forty-five percent were gender-diverse. Based on scales that assessed FTLBs (CGI-I) and overall functioning (CGI-S), up to 79% of patients improved independent of comorbid diagnosis or treatment. Evidence-based tic-specific treatments were not more effective than other treatments. A subset of patients had improvement in their FTLBs but not in their general functioning and continued to have other psychosomatic presentations. While many patients' FTLBs improved, it is critical to remain alert to patients' overall function and to assess for other functional neurological disorders and mental health concerns. The tendency of FTLBs to improve in this population, independent of treatment, highlights the unique pathophysiology of FTLBs. Future research on contributing psychosocial factors and specific treatment protocols will allow optimal support for these patients.

Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study.

Chronic insomnia disorder (CID) significantly impacts well-being and daily functioning. Daridorexant, a double orexin receptor blocker, has shown efficacy in randomized clinical trials and has been recently approved for the treatment of CID in adult patients. This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID. Consecutive patients initiating on-label daridorexant at the Sleep Medicine Centre, University Hospital of Rome Tor Vergata were enrolled. Baseline and 30-day follow-up (FU) evaluations included patients' and CID characteristics, comorbidities, and clinicians' and patients' subjective ratings of changes with the Clinical and Patient Global Impression-Improvement scores (CGI-Is and PGI-Is), as well as Insomnia Severity Index (ISI) scores in a subgroup of patients. Sixty-nine patients initiated 50-mg daily dosage. At FU, 58% of both patients and clinicians rated CID as improved on CGI-Is and PGI-Is, with no differences based on comorbidities, sex, or number of previous medications. No significant predictors of CGI-Is and PGI-Is improvement were identified. At FU, ISI scores (n = 24) significantly decreased from 18.25 ± 3.21 to 12.08 ± 6.12 (Z = 8.000; p < 0.001). Of these, eight patients (33.3%) had absence of insomnia symptoms, and no patients reported a worsening in ISI score categories. This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events. Future research on larger cohorts should explore daridorexant potential across diverse patient characteristics.

Atomoxetine Treatment of Attention Deficit/Hyperactivity Disorder Symptoms in 3-6-Year-Old Children with Autism Spectrum Disorder: A Retrospective Cohort Study.

Atomoxetine is indicated for the management of attention deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 18 years. Few studies have assessed the safety and tolerability of atomoxetine in younger patients. This retrospective cohort study included 133 children aged 3-6 years who were diagnosed with ADHD comorbid with autism spectrum disorder (ASD). The primary endpoint was the evaluation of the safety profile of atomoxetine. In total, 50 patients (37.6%) experienced adverse events (AEs), which led to treatment discontinuation in 23 patients (17.3%). The most common AEs were gastrointestinal (24.1%), aggression or hostility (12.8%), and increased hyperactivity (9.0%). In the 23 patients who discontinued treatment, all the AEs resolved after treatment ceased. Among the 110 patients who completed at least 6 months' treatment, atomoxetine titrated to a dose of 1.2-1.8 mg/kg/day appeared to be well tolerated and effective. The Clinical Global Impression-Improvement score improved to 1 ("very much improved") and 2 ("much improved") in 62.4% and 20.3% of children, respectively, at their last visit. Overall, atomoxetine appeared to be well tolerated in younger children with comorbid ADHD and ASD. Nevertheless, close patient monitoring remains essential, and the study limitations necessitate caution in generalizing these findings to broader populations. Long-term prospective studies are required.

Electroconvulsive therapy for adolescents with severe depressive episode and suicidality: retrospective comparison between responders and non-responders

BackgroundFor adolescents with major depression who exhibit suicidal tendencies, Electroconvulsive Therapy (ECT) is increasingly adopted in clinical practice. Yet, the precise mechanisms behind its effectiveness remain elusive, and studies on factors that influence treatment outcomes are scarce.MethodsIn this retrospective comparative study, we included all adolescent severe depressive episode patients with suicidal tendencies admitted to the Psychiatry Department of the First Affiliated Hospital of Chongqing Medical University between 2017 and 2021 and received ECT treatment. By collecting data on personal history, medical history, and standard treatment features, we established demographic, disease, medication, and ECT treatment factors variables. Patients were divided into effective and ineffective groups based on the Clinical Global Impressions-Improvement (CGI-I) scale scores, and differences between outcomes were compared. Logistic regression analyses were used to identify factors independently associated with ineffectiveness.ResultsA total of 494 adolescent severe depressive episode patients with suicidal behavior who received ECT were included in this study. According to CGI-I scores, the treatment was effective in 361 patients (73.1%) and ineffective in 133 patients (26.9%). Logistic regression analyses showed that 8 to 12 and 12 to 16 ECT sessions reduced the risk of ineffectiveness compared to fewer than 4 sessions. The risk of ineffectiveness decreased with age and increased with comorbidity with obsessive–compulsive disorder (OCD). Compared to sertraline, escitalopram was associated with a heightened risk of futility, whereas olanzapine and aripiprazole demonstrated a reduced risk when contrasted with quetiapine.ConclusionsECT's ineffectiveness in treating adolescent severe depressive episode with suicidal behavior decreases with age, and comorbidity with OCD significantly increases the risk of treatment failure. Fewer than 8 ECT sessions may hinder achieving satisfactory results.

Efficacy and Safety of SPN-812 (Extended-Release Viloxazine) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis.

SPN-812 has been approved for attention-deficit/hyperactivity disorder (ADHD) treatment in children and adolescents. We aimed to analyze the efficacy and safety of different doses of SPN-812 for ADHD pediatric patients of different ages, verify its clinical efficacy, and evaluate its safety. Up until 30 August 2023, randomized controlled trials (RCTs) were searched in EMBASE, MEDLINE, the Cochrane Library, and clinicaltrials.gov to evaluate different doses of SPN-812 and a placebo. We pooled 1619 patients from five RCTs with a duration of 6-8 weeks. Patients (6-17 years old) in SPN-812 (100, 200, and 400 mg/d) groups were superior to the control group in all efficacy outcomes with lower attention-deficit/hyperactivity disorder rating scale-5 (ADHD-RS-5), Conners 3-parent short form composite T score (Conners 3-PS), Weiss functional impairment rating scale-parent (WFIRS-P), and increased clinical global impression-improvement (CGI-I) score (both p < 0.05). At the same time, only SPN-812 300 mg/d did not show a significantly high risk of the adverse events (AEs) such as somnolence and decreased appetite (p = 0.09). There was no significant difference between placebo and SPN-812 groups (100, 200, and 400 mg/d) in serious adverse events (SAEs) such as syncope. The subgroup analyses showed that, both in children and adolescents subgroups, SPN-812 showed better efficacy than the placebo. The two age subgroups showed a significantly higher risk of AEs and an insignificant risk of SAEs than the placebo. At present, SPN-812 (100, 200, and 400 mg/d) is superior to the corresponding control in efficacy measures. However, the safety problem cannot be ignored.

Clinical implication of children's depression rating scale-revised score: Linking the children's depression rating scale-revised score and clinical global impression using patients data from clinical trials.

The Children's Depression Rating Scale-Revised (CDRS-R) score has been widely used to assess the severity of major depression in children and adolescents; however, the clinical implications of changes in the CDRS-R score remain unclear. We evaluated these clinical implications by assessing the relationship between changes in the CDRS-R score and changes in the Clinical Global Impression of Improvement (CGI-I), in clinical research on major depression. We used data from four clinical trials involving two antidepressants and evaluated the relationship between CDRS-R score changes and the CGI-I score using the equipercentile linking method. CDRS-R score changes corresponding to a minimally improved (score of 3) CGI-I score was approximately 14 points. Our findings from the linking analyses are useful for interpreting the clinical implications of changes in the CDRS-R score.

Effects of transcranial pulse stimulation on autism spectrum disorder: a double-blind, randomized, sham-controlled trial.

Transcranial pulse stimulation has been proven effective to improve cognition, memory and depressive symptoms of Alzheimer's disease, but supporting evidence on other neurological diseases or neuropsychiatric disorders remains limited. This study aimed to investigate the effects of transcranial pulse stimulation on the right temporoparietal junction, which is a key node for social cognition for autism spectrum disorder, and to examine the association between transcranial pulse stimulation and executive and social functions. This double-blinded, randomized, sham-controlled trial included 32 participants (27 males), aged 12-17 years with autism spectrum disorder. All eligible participants were randomized into either the verum or sham transcranial pulse stimulation group, on a 1:1 ratio, based on the Childhood Autism Rating Scale screening score. Sixteen participants received six verum transcranial pulse stimulation sessions (energy level: 0.2-0.25 mJ/mm2; pulse frequency: 2.5-4.0 Hz, 800 pulse/session) in 2 weeks on alternate days. The remaining 16 participants received sham transcranial pulse stimulation. The primary outcome measure included Childhood Autism Rating Scale score changes, evaluated by parents, from baseline to 3-month follow-ups. Secondary outcomes included a self-reported questionnaire responded to by parents and cognitive tests responded to by participants. A licensed mental health professional evaluated clinical global impression severity, improvement, efficacy and total score. Results revealed significant interactions in Childhood Autism Rating Scale and other secondary outcomes. Significant group and time effects were found in most secondary outcomes. Additionally, significant differences were found between the transcranial pulse stimulation and sham transcranial pulse stimulation groups in Childhood Autism Rating Scale and clinical global impression improvement and total score immediately after 2 weeks of transcranial pulse stimulation intervention (all P < 0.05), and effects were sustainable at 1- and 3-month follow-up, compared with baseline. The effect size of Childhood Autism Rating Scale (d = 0.83-0.95) and clinical global impression improvement (d = 4.12-4.37) were large to medium immediately after intervention and sustained at 1-month post-stimulation; however, the effects were reduced to small at 3-month post-stimulation (d = 2.31). These findings indicated that transcranial pulse stimulation over right temporoparietal junction was effective to reduce the core symptoms of autism spectrum disorder, as evidenced by a 24% reduction in the total Childhood Autism Rating Scale score in the verum transcranial pulse stimulation group. Additionally, the clinical global impression total score was reduced by 53.7% in the verum transcranial pulse stimulation group at a 3-month follow-up, compared with the baseline. Participants in the verum transcranial pulse stimulation group had shown substantial improvement at 1- and 3-month follow-ups, compared with baseline, although some of the neuropsychological test results were deemed statistically insignificant. Future replication of this study should include a larger sample derived from multi-nations to determine transcranial pulse stimulation as an alternative top-on treatment option in neuropsychiatry.

Alternative psychopharmacologic treatments for pediatric catatonia: a retrospective analysis.

Pediatric catatonia is a highly co-morbid condition with treatment options often limited to electroconvulsive therapy (ECT) or lorazepam. However, lorazepam may not be readily available, and access to ECT is limited by restrictive legislation and stigma. This study aims to provide alternative treatment options for pediatric catatonia. The study involved a single-site retrospective analysis of a private university hospital in the southern United States. The study included patients under eighteen with catatonia who received psychopharmacologic treatment with an agent other than lorazepam. The patients were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), and Kanner Catatonia Examination (KCE) at the time of initial evaluation and upon stabilization. A retrospective clinical global impressions-improvement (CGI-I) score was assigned by four authors. 102 pediatric patients diagnosed with catatonia were identified, and 31 met criteria for the study. 20 (65%) were white, 6 (19%) were Black, 4 (13%) were Hispanic, and 1 (3%) were Indian. Most patients (N = 18; 58%) were insured by Medicaid. The mean age at the time of catatonia diagnosis was 13.5 years. All patients were stabilized on either clonazepam or diazepam, with 21 (68%) requiring treatment with an additional medication of either an anti-epileptic, N-methyl-D-aspartate (NMDA) receptor antagonist, and aripiprazole or clozapine. Statistically significant reductions in the BFCRS [t = 11.2, df = 30, std = 6.3, p < 0.001, 95% CI = (7.8, 15.1)], KCS [t = 4.6, df = 38, p < 0.001, 95% CI = (12.0, 31.0)], and KCE [t = 7.8, df = 30, std = 1.8, p < 0.001, 95% CI = (1.9, 3.2)] were observed. For CGI-I the results showed that the estimated probability of observing a score better than no change (>4) is 0.976 [t.s. = 43.2, p < 0.001, 95% CI = (0.931,0.992)], indicating the average subject is expected to experience some improvement. In conclusion, all patients responded to these treatments with improvement in their catatonic symptoms. Alternative pharmacologic interventions for catatonia, including benzodiazepines other than lorazepam, valproic acid, NMDA receptor antagonists, and atypical antipsychotics were safe and effective in treating catatonia in this population.

Safety and efficacy of aripiprazole 2-month ready-to-use 960 mg: secondary analysis of outcomes in adult patients with bipolar I disorder in a randomized, open-label, parallel-arm, pivotal study

Objective Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable antipsychotic formulation for administration every 2 months. A 32-week trial evaluated the safety, tolerability, and pharmacokinetics of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I) (per DSM-5 criteria). This secondary analysis evaluated the safety and efficacy of Ari 2MRTU 960 in the subpopulation of patients with BP-I. Methods Patients with BP-I were randomized to receive Ari 2MRTU 960 (n = 40) every 56 ± 2 days (4 injections scheduled) or aripiprazole once-monthly 400 mg (AOM 400; n = 41) every 28 ± 2 days (8 injections scheduled). Data were collected during August 2019–July 2020 across 16 US sites. Primary safety endpoints included reported adverse events (coded by the Medical Dictionary for Regulatory Activities preferred term), injection site reactions (assessments included a Visual Analog Scale [VAS] to evaluate patient-reported injection-site pain), and motoric symptoms. Secondary endpoints for efficacy included change from baseline at Week 32 in the Young Mania Rating Scale (YMRS), Montgomery–Åsberg Depression Rating Scale (MADRS), Clinical Global Impression – Bipolar Version (CGI-BP), and Subjective Well-being under Neuroleptic Treatment – Short Form (SWN-S) scores, and Clinical Global Impression – Improvement (CGI-I) at Week 32. Results The incidence of treatment-emergent adverse events (TEAEs) was similar between Ari 2MRTU 960 (82.5% [33/40]) and AOM 400 (87.8% [36/41]; p = .5468). The most frequently reported TEAE was increased weight (Ari 2MRTU 960: 25.0% [10/40]; AOM 400: 26.8% [11/41]; p = 1). Injection-site pain was experienced by more patients in the Ari 2MRTU 960 group (25% [10/40]) versus the AOM 400 group (7.3% [3/41]; p = .0622). Mean (standard deviation [SD]) VAS scores for patient-reported injection-site pain following the last injection were 1.2 (2.07) for Ari 2MRTU 960 group and 1.3 (2.19) for AOM 400 (p = .9479) (VAS scale range 0–100 [no pain–extreme pain]). No notable improvement or decline from baseline was observed in motoric symptoms in either treatment group. Patients in both treatment groups remained clinically stable for the entire 32-week trial duration, with minimal difference between treatment groups in the least squares (LS) mean change from baseline at Week 32 in the YMRS Total (p = .8995), MADRS Total (p = .3185), and CGI-BP scores (p = .8485), and in mean CGI-I score (p = .7960). LS mean change from baseline in SWN-S score was greater for Ari 2MRTU 960 than for AOM 400 at Week 32 (p = .0169). Conclusions Ari 2MRTU 960 was well tolerated in patients with BP-I, with efficacy similar to AOM 400. Trial registration ClinicalTrials.gov identifier: NCT04030143.

Outcome in Pediatric Functional Tic Disorders Diagnosed During the COVID-19 Pandemic.

The incidence of pediatric functional tics has surged during the COVID-19 pandemic with little known about prognosis. To address this knowledge gap, the investigators examined clinical courses of functional tics diagnosed during the pandemic and explored factors predicting prognosis. Study personnel reviewed electronic medical records of 29 pediatric patients diagnosed as having functional tics between March 1, 2020, and December 31, 2021, and estimated Clinical Global Impression-Improvement (CGI-I) scores at follow-up encounters. Twenty patient-guardian dyads completed telephone interviews. Logistic regression models were used to identify possible predictors of clinical trajectories. Of the 29 patients, 21 (82%) reported at least some improvement since diagnosis at the time of the last follow-up, with a median CGI-I score of 2 (much improved). During the telephone interview, 11 of 20 patients noted ongoing interference from tics, and 16 of 20 agreed with the diagnosis of functional tics. Median time from symptom onset to diagnosis was 197 days, with most patients reporting at least a mild reduction of symptoms (CGI-I score <4) at a median of 21 days after diagnosis. At a median follow-up time of 198 days after diagnosis, patients reported significant but not complete improvement. Greater age and longer time to diagnosis decreased odds of improvement within 1 month of diagnosis. Most patients showed improvements in but not the resolution of functional tic symptoms after diagnosis. These data support the importance of early diagnosis for functional tics.

Safety and Efficacy of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Bipolar I Disorder

AbstractBackgroundAripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months. This 32-week trial evaluated the safety, pharmacokinetics, and efficacy of multiple-dose administration of Ari 2MRTU 960 in clinically stable adults with schizophrenia or BP-I, versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole and maintenance monotherapy treatment of BP-I [indication varies by country]). Safety and efficacy outcomes in the subpopulation of patients with BP-I are reported here.MethodsPatients with BP-I were randomized to receive Ari 2MRTU 960 every 56±2 days or AOM 400 every 28±2 days. Safety and tolerability assessments included adverse event (AE) reporting, Visual Analogue Scale (VAS) scores (scale range: 0–100) for patient-reported injection site pain, and extrapyramidal symptom (EPS) monitoring. Efficacy was assessed at Week 32 by Clinical Global Impression – Improvement (CGI-I), Clinical Global Impression – Bipolar Version (CGI-BP), Subjective Well-being under Neuroleptic Treatment – Short Form (SWN-S), Montgomery–Åsberg Depression Rating Scale (MADRS), and Young Mania Rating Scale (YMRS).ResultsStudy completion rate was 72.5% (29/40 patients) in the Ari 2MRTU 960 group and 70.7% (29/41 patients) in the AOM 400 group. Demographics and baseline disease characteristics were generally well balanced between treatment groups. Treatment-emergent AE (TEAE) incidence was 82.5% with Ari 2MRTU 960 and 87.8% with AOM 400. The most frequent TEAEs were increased weight (Ari 2MRTU 960, 25.0%; AOM 400, 26.8%) and injection site pain (Ari 2MRTU 960, 25.0%; AOM 400, 7.3%). Mean (standard deviation [SD]) VAS score for pain after last injection was 1.2 (2.07) with Ari 2MRTU 960 and 1.3 (2.19) with AOM 400. Minimal change was seen in EPS in either group. At Week 32, mean (SD) CGI-I score was 3.1 [1.2] with Ari 2MRTU 960 and 3.2 [1.5] with AOM 400, and there was minimal mean (SD) change from baseline in CGI-BP score (Ari 2MRTU 960, -0.2 [1.0]; AOM 400, -0.6 [1.2]). Mean (SD) change from baseline in SWN-S Total score was 10.3 (16.1) with Ari 2MRTU 960 and 3.4 (21.4) with AOM 400. There was no clinically meaningful difference between the groups in MADRS Total score or YMRS Total score (difference of least squares mean change from baseline [95% confidence interval]: MADRS Total score -2.1 [-6.3, 2.1], p=0.3185; YMRS Total score 0.1 [-1.8, 2.1], p=0.8995).ConclusionsIn patients with BP-I, Ari 2MRTU 960 was generally well tolerated, and clinical stability was maintained during the study.FundingOtsuka Pharmaceutical Development &amp; Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).

Safety And Efficacy of Aripiprazole 2-Month Ready-to-Use 960 mg in Adult Patients With Schizophrenia

AbstractBackgroundAripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a new long-acting injectable (LAI) antipsychotic formulation for gluteal administration every 2 months. This 32-week trial evaluated the safety, pharmacokinetics, and efficacy of multiple-dose administration of Ari 2MRTU 960 in clinically stable adults with schizophrenia or bipolar I disorder (BP-I), versus that of aripiprazole once-monthly 400 mg (AOM 400; an LAI indicated for the maintenance treatment of schizophrenia in adult patients stabilized with oral aripiprazole [indication varies by country]). Safety and efficacy outcomes in the subpopulation of patients with schizophrenia are reported here.MethodsPatients with schizophrenia were randomized to receive Ari 2MRTU 960 every 56±2 days or AOM 400 every 28±2 days. Safety and tolerability assessments included adverse event (AE) reporting, Visual Analogue Scale [VAS] scores (scale range: 0–100) for patient-reported injection site pain, and extrapyramidal symptom (EPS) monitoring. Efficacy was evaluated at Week 32 using mean (standard deviation [SD]) Clinical Global Impression – Improvement (CGI-I) score, and mean (SD) change from baseline in Clinical Global Impression – Severity (CGI-S) score, Subjective Well-being under Neuroleptic Treatment – Short Form [SWN-S] Total score, and Positive and Negative Syndrome Scale (PANSS) Total score.ResultsStudy completion rate was 79.3% (73/92 patients) in the Ari 2MRTU 960 group and 67.7% (63/93 patients) in the AOM 400 group. Demographics and disease characteristics were well balanced between groups at baseline (mean [SD] PANSS Total score: Ari 2MRTU 960, 62.0 [13.5]; AOM 400, 61.8 [13.5]; mean (SD) CGI-S score: Ari 2MRTU 960, 3.3 [0.9]; AOM 400, 3.1 [0.9]). Treatment-emergent AE (TEAE) incidence was 66.3% with Ari 2MRTU 960 and 63.4% with AOM 400. The most frequent TEAEs were increased weight (Ari 2MRTU 960, 21.7%; AOM 400, 18.3%) and injection site pain (Ari 2MRTU 960, 15.2%; AOM 400, 9.7%). Mean (SD) VAS score for pain after last injection was 1.5 (4.58) with Ari 2MRTU 960 and 1.3 (2.79) with AOM 400. Minimal change was seen in EPS in either group. At Week 32, mean (SD) CGI-I score was similar between groups (Ari 2MRTU 960, 3.5 [1.0]; AOM 400, 3.6 [0.9]). Minimal change from baseline was seen at Week 32 in CGI-S score and SWN-S Total score. There was no clinically meaningful difference between the groups for PANSS Total score (difference of least squares mean change from baseline [95% confidence interval]: -0.9 [-3.5, 1.8]; p=0.5154).ConclusionsIn patients with schizophrenia, administration of Ari 2MRTU 960, as compared with AOM 400, was generally well tolerated, and clinical stability was maintained during the study.FundingOtsuka Pharmaceutical Development &amp; Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).

Another Option for Aggression and Self-Injury, Alternative Benzodiazepines for Catatonia in Profound Autism.

Introduction: Individuals with profound autism often present for inpatient care due to aggression. Diagnostic and treatment options are limited. Agitated catatonia is a treatable comorbidity in autism, which should be considered in cases of aggression. Preliminary data report high clinical response rates of catatonia in autism when treated with electroconvulsive therapy (ECT), with poor response to lorazepam. However, access to ECT is often limited, especially in pediatric populations. Methods: We conducted a retrospective chart review to identify cases of hyperactive catatonia with partial response to lorazepam in profoundly autistic children presenting to the pediatric medical hospital. Five cases were identified, all of whom were followed by the child and adolescent psychiatry consult-liaison service during admission and treated without the use of ECT. Data from the medical record were obtained after institutional review board (IRB) approval including the following: (1) treatment course, (2) Bush-Francis Catatonia Rating Scale (BFCRS) scores, and (3) Kanner Catatonia Rating Scale (KCRS) severity scores. The Clinical Global Impressions-Improvement (CGI-I) Scale was applied retrospectively to each case. Results: All five patients demonstrated clinically significant improvements. The average CGI-I score was 1.2. The average percentage reduction in the BFCRS and KCRS severity scores was 63% and 59%, respectively. Two of five patients were first stabilized with infusions midazolam and dexmedetomidine due to the symptom severity and then transitioned to long-acting oral benzodiazepines. Overall, four of five patients were stabilized with oral clonazepam and one of five with oral diazepam. Notably, four of five patients experienced an acute worsening of aggression, self-injury, and other catatonic symptoms with escalating dosages of antipsychotic treatment, which occurred before inpatient admission. All patients experienced resolution of physical aggression toward self and/or others, experienced improvement in their communicative abilities, and were able to return home or enter residential level of care upon discharge. Conclusions: Given the limited availability of ECT and the unclear utility of lorazepam for hyperactive catatonia in autism, the use of long-acting benzodiazepines and/or midazolam infusion may offer a safe and readily available treatment alternative.

Outcome of transcranial magnetic intermittent theta-burst stimulation in the treatment of depression - A Swedish register-based study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response. MethodsData was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis. ResultsThe response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65–7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported. LimitationsRetrospective analysis of register data. No comparison group. ConclusionsIn a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.

Effectiveness of vortioxetine in patients with major depressive disorder and comorbid Alzheimer's disease in routine clinical practice: An analysis of a post-marketing surveillance study in South Korea.

Vortioxetine has demonstrated procognitive effects in patients with major depressive disorder (MDD). We assessed the effectiveness and safety of vortioxetine in a cohort of patients with MDD and comorbid Alzheimer's disease participating in a large post-marketing surveillance study in South Korea. Subgroup analysis of a 6-month, prospective, multicenter, non-interventional cohort study in outpatients with MDD with a pre-baseline diagnosis of Alzheimer's disease receiving vortioxetine in routine care settings (n = 207). Patients were assessed at baseline and after 8 weeks; a subset of patients was also assessed after 24 weeks. Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) scale, cognitive symptoms using the Perceived Deficits Questionnaire-Depression, Korean version (PDQ-K), and cognitive performance using the Digit Symbol Substitution Test (DSST). Most patients were receiving a mean daily vortioxetine dose of 5 mg/day (174/190 patients; 91.6%). After 24 weeks of vortioxetine treatment, 71.4% of patients (40/56) had experienced overall clinical improvement (i.e., CGI-Improvement score ≤3) and 51.9% (28/54) had achieved remission from depressive symptoms (i.e., MADRS total score ≤10 points). Respective mean changes in MADRS, PDQ-K, and DSST total scores from baseline to week 24 were -11.5 (p < 0.0001), -5.1 (p = 0.03), and +3.8 points (p = 0.0524). Adverse events were reported by 27 patients (13.0%) and were mostly mild (89.2%). Patients with MDD and comorbid Alzheimer's disease receiving vortioxetine in routine care settings in South Korea demonstrated clinically meaningful improvements in depressive symptoms, cognitive symptoms, and objective cognitive performance over the 6-month treatment period. Treatment with vortioxetine was well tolerated in this patient cohort, with reported adverse events consistent with the established tolerability profile of vortioxetine.