Clinical Global Impressions-Improvement Score Research Articles

Randomized, Double-Blind, Placebo-Controlled, Flexible-Dose Titration Study of Methylphenidate Hydrochloride Extended-Release Capsules (Aptensio XR) in Preschool Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: To assess the efficacy and safety of a methylphenidate hydrochloride extended-release capsule (MPH-MLR) formulation in treating attention-deficit/hyperactivity disorder (ADHD) in preschool children.Methods: Children aged 4 to <6 years with qualifying ADHD Rating Scale Fourth Edition (ADHD-RS-IV) Preschool Version scores (≥90th percentile for age/gender) participated in four behavior management training (BMT) sessions or immediately entered (based on investigator assessment of symptom severity or previous participation) into a 6-week, open-label, flexible MPH-MLR dose optimization phase. After BMT, children with <30% improvement in ADHD-RS-IV score and ≥3 score on the Clinical Global Impression—Improvement (CGI-I) scale also entered the open-label period. All children began the open-label period with MPH-MLR 10 mg once daily; weekly adjustments permitted once-daily maximum of up to 40 mg. Children with ≥30% improvement in ADHD-RS-IV total score and a CGI-I score of 1–2 at open-label completion were randomized to their optimized dose of MPH-MLR or placebo for 2 weeks (double blind [DB]). Safety measures included adverse events (AEs), vital signs, and electrocardiograms.Results: Open-label enrollment was 119 children. Mean (SD) ADHD-RS-IV total scores at open-label start and open-label end was 40.8 (10.4) and 19.5 (11.1), respectively. Ninety children were enrolled in the DB phase. Mean (SD) ADHD-RS-IV total scores for the MPH-MLR and placebo group were similar at DB beginning and was 25.8 (14.6) and 34.9 (14.1), respectively, at DB end. Mean change from baseline in ADHD-RS-IV total score during DB was significantly greater in children randomized to placebo compared with MPH-MLR; least squares mean change difference from baseline was −11.2, p = 0.002. During open-label dosing, the most common AEs (≥10%) were decreased appetite, decreased weight, insomnia, hypertension, emotional disorder, and affect lability.Conclusion: Results demonstrate MPH-MLR efficacy in preschool children and a safety profile consistent with known AEs of methylphenidate when used for ADHD.

Post hoc analyses of response rates to pharmacological treatments in children and adolescents with attention-deficit/hyperactivity disorder.

Introduction and objectives:Lack of consensus regarding how best to define treatment response hinders translation from trials to the clinic. These post hoc analyses examine three commonly used response criteria in six trials of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).Methods:Data from four short-term randomised controlled trials (RCTs) and two long-term open-label studies were analysed. Children and adolescents with ADHD received either dose-optimised (30–70 mg/day) or fixed-dose (70 mg/day) LDX. The RCTs included osmotic-release oral system methylphenidate (OROS-MPH) or atomoxetine (ATX) as a head-to-head comparator or as a reference treatment. Three definitions of response were used in these analyses: reductions of ⩾30% or ⩾50% in ADHD Rating Scale IV (ADHD-RS-IV) total score plus a Clinical Global Impressions – Improvement (CGI-I) score of 1 or 2, or an ADHD-RS-IV total score of ⩽18.Results:At the end point, LDX response rates for the least stringent criterion of ⩾30% reduction in ADHD-RS-IV total score plus a CGI-I score of 1 or 2 ranged from 69.6% to 82.6%. The proportion achieving the more stringent criterion of a reduction in ADHD-RS-IV total score of ⩾50% plus a CGI-I score of 1 or 2 at the end point ranged from 59.8% to 74.8%. An ADHD-RS-IV total score of ⩽18 at the end point was achieved by 56.7–79.9% of participants. Response rates remained stable throughout the long-term open-label studies.Conclusions:Response rates were similar for the two more stringent response criteria. The less stringent criterion resulted in higher response rates and may include partial responders.

Is Low FODMAP Diet Effective in Children with Irritable Bowel Disease?

OBJECTIVE:There is growing evidence that suggests that consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may result in some symptoms in certain patients with irritable bowel syndrome (IBS). This study aims to evaluate the efficacy of a low FODMAP diet in children with IBS by comparing it with the standard diet.METHODS:Sixty children between the ages of 6 and 18 who were diagnosed with IBS according to Rome IV criteria were included in this study. Randomly selected patients were divided into two groups as 30 patients on a low FODMAP diet and 30 patients on a general protective standard diet for the gastrointestinal tract. Patients were evaluated at the beginning, second and fourth months of the study. The data of the patients were recorded in the demographic data form. Patients were asked to score abdominal pain using the Visual Analogue Scale (VAS). The clinical status of the patient was scored by the doctor using the Clinical Global Impression Improvement (CGI-I) scale.RESULTS:There were no significant differences between groups about age, sex and symptom duration. When the pre-diet VAS scores were compared, the two groups were similar. The mean decrease in VAS score after two months of diet was 3.80±1.10 in the low FODMAP group and 2.03±1.03 in the standard group and was statistically significant. Post-dietary CGI-I score evaluation was determined to be statistically significant between the two groups. The increase in VAS scores in the fourth month was 2.97±1.10 points in the Low FODMAP group and 1.63±0.71 in the standard group, and was statistically significant. CGI-I score after the diet at the 4th month was also statistically significant between the two groups.CONCLUSION:A low FODMAP diet seems to be more effective for symptom control in IBS when compared to standard dietary advice. Further studies are needed for the unknowns that will be used in clinical practice, such as how long the diet will be continued and how effective it will be in which GIS diseases.

Predictors of Treatment Response to Electroconvulsive Therapy in Schizophrenia—A Nationwide Registry-Based Study

AbstractIntroductionUp to 30% of patients with schizophrenia respond insufficiently to antipsychotic drugs. Electroconvulsive therapy (ECT) has been reported to effectively augment the effects of antipsychotics in some of these patients. To date, there are few established predictors of treatment response to ECT in patients with schizophrenia.AimsThe primary aim was to determine the response rate to ECT in patients with schizophrenia. The secondary aim was to investigate predictors of treatment response.MethodsAll patients admitted to any Swedish hospital for schizophrenia from 2011 to 2017, who were treated with ECT while in inpatient care, were included in the Swedish National Quality Registry for ECT (Q-ECT), and were assessed using the Clinical Global Impression – Improvement (CGI-I) scale after treatment were included. CGI-I scores of 1 or 2 were considered a response to treatment. Multiple national registries were used to obtain information on demographics and clinical variables.ResultsThe study included 285 patients who were concurrently treated with antipsychotic drugs. The response rate to ECT was 73.0%. Among those patients with outcome data, treatment with long-acting injectable antipsychotics was predictive of a better response, whereas comorbid substance use disorders were predictive of a worse response.ConclusionThis study provides new evidence on predictors of who might respond among patients with schizophrenia treated by ECT. Additional studies of ECT in schizophrenia are needed.

A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder

Objectives: This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of attention deficit/hyperactivity disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD).Methods: A 6-week open-label trial (ClinicalTrials.gov: NCT02096952) was conducted in 15 HF-ASD adults (mean age 24.9 ± 4.6; male, 12 (80%)) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures.Results: Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale (AISRS) mean change (MC), −22.8 ± 8.8, P < 0.001; Adult ADHD Self-Report Scale (ASRS) MC, −8.2 ± 15.3, P < 0.001). Twelve (80%) participants were deemed responders, based on ≥30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score ≤2. MPH-ER was well-tolerated (treatment-limiting AEs, 1/15; severe AEs, 1/15) at mean dose of 48.7 ± 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache (53%), insomnia (33%), anxiety (33%), decreased appetite (27%)).Conclusions: Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

Randomized, single blinded comparative study of selective serotonin reuptake inhibitor augmentation with olanzapine v/s amisulpride for obsessive compulsive disorder

Background: Obsessive-Compulsive Disorder is classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) as an anxiety disorder. Serotonin reuptake inhibitors are considered to be most effective and are the first line pharmacotherapy for the treatment of OCD. However, about 40-60% of OCD patients fail to respond to SSRI mono-therapy. Further, as many as 25% of patients fails to experience any improvement from initial SSRIs mono-therapy. For non-responder’s low dose augmentation with antipsychotics (risperidone, quetiapine, olanzapine, aripirazole, amisuplride etc.) has shown promising response, as compared to serotonin enhancers. The present study is designed to evaluate and compare the efficacy and adverse drug reactions of these two antipsychotics viz. Olanzapine and amisulpride as augmentation strategy in OCD patients. Objective of present study was to compare the efficacy of olanzapine and amisulpride as add on therapy for inadequately controlled obsessive-compulsive disorder patients on selective-serotonin reuptake inhibitor.Methods: the present study was done at Medical College Jabalpur (M.P.) in the department of Psychiatry &amp; Pharmacology. It was randomized, patient blinded study. 47 patients were screened for the study out of which 36 were enrolled and randomized into either SSRI+Olanzapine or SSRI+Amisulpride group. The patients were evaluated at baseline and then biweekly for 12 weeks to assess the efficacy of these drugs as augmentation strategy using Yale-Brown Obsessive Compulsive Scale (Y-BOCS).Results: There was a significant improvement in Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Clinical Global Impression-Severity (CGI-S) score and Clinical Global impression-Improvement (CGI-I) score in both the groups but there was no significant difference (P&gt;0.05) in either of these groups on these three scale. No serious adverse drug reaction was reported in either of these groups.Conclusions: Both olanzapine and amisulpride are efficacious and well tolerated for augmentation of SSRI with no significant difference in their efficacy.

Selective Serotonin Reuptake Inhibitor Monotherapy for Anxiety Disorders in Children and Adolescents with Autism Spectrum Disorder: A Chart Review.

Objective: Anxiety disorders are one of the most commonly co-occurring psychiatric diagnoses in youth with autism spectrum disorder (ASD), with a frequency ranging from 22% to 84%. Methods: We conducted a chart review of 29 children and adolescents with ASD who had been treated with selective serotonin reuptake inhibitor (SSRI) monotherapy for an anxiety disorder for at least 2 months. Subsequent chart reviews were conducted for the first follow-up visit within 2-6 months (M = 4.2 months) and the visit closest to 9 months posttreatment (ranging from 7 to 12 months; M = 10.5 months). The presence of adverse events (AEs) was examined, and a consensus Clinical Global Impressions Improvement (CGI-I) score was determined. Results: Fifty-five percent of patients were given a CGI-I of "improved" or "very much improved" at the 9-month follow-up. Four patients discontinued treatment owing to AEs. Other reported AEs not leading to discontinuation included vivid dreaming, increased emotional lability, and irritability. Responders included a number of patients who had failed previous SSRI trials. Conclusions: This study suggests that SSRI treatment should be considered for individuals with ASD and anxiety disorders, even if prior SSRI trials have been unsuccessful.

Brief Behavioral Therapy for Pediatric Anxiety and Depression in Primary Care: A Follow-up

To report on the 32-week outcome of the Brief Behavioral Therapy (BBT) for Pediatric Anxiety and Depression in Primary Care clinical trial. A total of 185 youths aged 8 to 17 years with anxiety and/or depression identified through 9 pediatric primary care (PPC) settings in San Diego and Pittsburgh were randomized to receive Assisted Referral to Care (ARC) or up to 12 sessions of BBT over 16 weeks. The primary outcome was clinical response across anxiety and depression, defined as a Clinical Global Impressions-Improvement Score of≤2. Secondary outcomes included interview-rated functioning, depression, and anxiety. Here, we report on outcomes at 32 weeks after randomization. All analyses with primary outcomes are corrected for multiple comparisons using the false discovery rate procedure. At 32 weeks, BBT was superior to ARC with respect to response (67.5% versus 43.1%, q= 0.03, number needed to treat [NNT]= 5) and functioning (d= 0.49, q= 0.04). BBT was superior to ARC with respect to its impact on anxiety (f= 0.21) but not depressive symptoms (f= 0.05). These findings persisted after controlling for the number of sessions received. Ethnicity moderated the impact of BBT on outcome (NNT for Hispanic youths= 2), because of a much lower response rate to ARC in Hispanic than in non-Hispanic youths (16.7% versus 49.2%, p= 0.04). BBT is a promising intervention that can be effectively delivered in PPC and may be particularly effective for Hispanic patients. Further work is indicated to improve its impact on depressive symptoms and to test BBT against other treatments delivered in pediatric primary care. Brief Cognitive Behavioral Therapy (CBT) for Pediatric Anxiety and Depression in Primary Care; http://clinicaltrials.gov; NCT01147614.

Behavioral activation therapy for depression and anxiety in cancer patients: a case series study

BackgroundBehavioral activation therapy (BAT) directly addresses activities that individuals value most highly, and may be easily applicable to cancer patients. However, there is no established evidence of the use of BAT in this population. In this study, we examined the possibility of a BAT program for depression and anxiety in cancer patients.Case presentationWe retrospectively reviewed the medical records of cancer patients with each of the following characteristics: 1) were outpatients or inpatients visiting the psycho-oncology division of the National Cancer Center Hospital in Japan; 2) met criteria for Major Depressive Disorder or Adjustment Disorders; and 3) participated in a BAT program. The primary outcome was the program completion percentage. Secondary outcomes were self-reported depression severity (Patient Health Questionnaire-9 (PHQ-9) score), anxiety disorder status (Generalized Anxiety Disorder-7 (GAD-7) score), and clinical improvement (Clinical Global Impression-Improvement (CGI-I) score) after the program. We analyzed both depression and anxiety by the matched paired t-test. Ten patients participated in the program, and nine completed it. One dropped out due to cognitive impairment secondary to brain metastasis. Both the PHQ-9 scores (pre: 14.4 (SD, 6.1); post: 5.1 (SD, 5.8)) and the GAD-7 scores (pre: 11.9 (SD, 4.9); post: 4.7 (SD, 5.5)) significantly improved after the program (PHQ-9: P = 0.0014; GAD-7: P = 0.0004). CGI-I scores ranged from 1 to 3, and all subjects except the patient who dropped out improved clinically. Among the ten patients, three distinctive cases could be observed as follows. Case 1; a 45-year-old housewife with breast cancer who did not agree to take antidepressants because of concerns about the side effects achieved remission without antidepressants and began to live an active life. Case 4; a 66-year-old housewife was so shocked after endometrial cancer diagnosis that she was absent-minded and her compliance with the assigned homework was poor, therefore, her depression did not improve much. Case 9; a 62-year-old man with laryngeal cancer who had recurrent anxiety. Increased business activity, on which he put great value, gradually allowed him to be able to live his life actively without concerns.ConclusionsThis study suggests that BAT would be effective for the depression and anxiety of cancer patients.

Clonazepam for probable REM sleep behavior disorder in Parkinson's disease: A randomized placebo-controlled trial

BackgroundClonazepam is considered to be a first-line treatment for rapid eye movement sleep-related behavior disorder (RBD) in Parkinson's disease (PD). The purpose of this study was to determine the short-term efficacy and safety of clonazepam for the treatment of probable RBD (pRBD) in patients with PD. MethodsWe conducted a four-week, randomized, double-blind, placebo-controlled trial of clonazepam (0.5 mg/day at bedtime) compared to a placebo for RBD symptoms in patients with PD. Patients aged 30 years or older who had a caregiver that could observe RBD symptoms were recruited between April 2015 and February 2016. The primary outcome was the Clinical Global Impressions-Improvement (CGII) score at week four, and we compared scores between the clonazepam and placebo groups. ResultsA total of 40 patients were enrolled, with 20 assigned to receive clonazepam and 20 to receive the placebo. The CGI-I score at four weeks indicated an improvement in RBD symptoms in both the clonazepam (median score [minimum, maximum] = 2 [1,5]) and placebo (3 [1,6]) groups, with no significant difference between the groups (p = .253). The secondary outcomes were not significantly different between the clonazepam and placebo groups. ConclusionsBoth clonazepam and placebo tended toward improvement on pRBD symptoms in patients with PD. No firm conclusion on efficacy of clonazepam was drawn due to limitations in the study design. This study emphasized the importance of conducting future large-scale, randomized trials with better assessment tools and polysomnography to provide evidence for the benefit of clonazepam.

Characteristics of ADHD Symptom Response/Remission in a Clinical Trial of Methylphenidate Extended Release.

Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR®) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score ≤18) was most closely aligned with a ≥46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a ≥40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint.

A Phase II Double-Blind, Placebo-Controlled, Efficacy and Safety Study of SPN-812 (Extended-Release Viloxazine) in Children With ADHD

Objective: The objective of this study is to evaluate efficacy and safety of SPN-812 (extended-release viloxazine) for ADHD in children aged 6 to 12 years. Method: In an 8-week study, 222 participants were randomized to placebo or SPN-812 100, 200, 300, or 400 mg/day. Measurements included ADHD Rating Scale (RS)-IV total score and Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scores. Safety assessments included laboratory and electrocardiogram (ECG) measurements, suicidality monitoring (Columbia-Suicide Severity Rating Scale), and adverse event (AE) reporting. Results: Significant improvements in ADHD-RS-IV total score were observed for 200, 300, and 400 mg dose groups versus placebo (p < .05; effect size [ES] = 0.547, 0.596, and 0.623). CGI-I score for the 300 mg group and CGI-S score for all SPN-812 groups except for 100 mg improved significantly (p < .05) versus placebo. The most frequent AEs (≥15%) were somnolence, headache, and decreased appetite. Conclusion: SPN-812 significantly reduced the severity of ADHD symptoms and was well tolerated. The efficacy and safety of SPN-812 are being investigated in Phase III trials.

Linking PANSS negative symptom scores with the Clinical Global Impressions Scale: understanding negative symptom scores in schizophrenia

Understanding how rating scale improvement corresponds to a clinical impression in patients with negative symptoms of schizophrenia may help define the clinical relevance of change in this patient population. We conducted post hoc equipercentile linking analyses of Positive and Negative Syndrome Scale (PANSS) outcomes (e.g., PANSS-Factor Score for Negative Symptoms [FSNS]) with Clinical Global Impressions-Improvement (CGI-I) and -Severity (CGI-S) ratings on data from patients treated with cariprazine (n = 227) or risperidone (n = 229) in a clinical study evaluating negative symptoms in schizophrenia. Patients were prospectively selected for persistent, predominant negative symptoms of schizophrenia (PNS), and minimal positive/depressive/extrapyramidal symptoms. Linking results demonstrated that greater improvement on PANSS-derived measures corresponded to clinical impressions of greater improvement, as measured by the CGI-I, and less severe disease states, as measured by the CGI-S. For example, CGI-S scores of 1 (normal), 2, 3, 4, 5, and 6 (severely ill) corresponded to PANSS-FSNS scores of 7, 13, 19, 24, 29, and 35, respectively. Likewise, CGI-I scores of minimally improved, much improved, and very much improved corresponded to a change from baseline in PANSS-FSNS scores of −27%, −49%, and −100%, respectively. These are important findings for the interpretation of the results of trials in patients with persistent negative symptoms.

Effects of melatonin in children with attention-deficit/hyperactivity disorder with sleep disorders after methylphenidate treatment.

PurposeMethylphenidate (MPH), the first-line medication in children with attention-deficit/hyperactivity disorder (ADHD), is associated with increased risk of sleep disorders. Melatonin has both hypnotic and chronobiotic properties that influence circadian rhythm sleep disorders. This study explores the effectiveness of melatonin in children with ADHD who developed sleep problems after starting MPH.Patients and methodsThis study, based on a clinical database, included 74 children (69 males, mean age 11.6±2.2 years) naturalistically treated with MPH (mean dosage 33.5±13.5 mg/d). The severity of sleep disorder (sleep onset delay) was recorded at baseline and after a follow-up of at least 4 weeks using a seven-point Likert scale according to the Clinical Global Impression Severity score. Effectiveness of melatonin on sleep (mean dosage 1.85±0.84 mg/d) after 4 weeks was assessed using a seven-point Likert scale according to the Clinical Global Impression Improvement (CGI-I) score, and patients who scored 1 (very much improved) or 2 (much improved) were considered responders.ResultsClinical severity of sleep disorders was 3.41±0.70 at the baseline and 2.13±1.05 after the follow-up (P<0.001). According to the CGI-I score, 45 patients (60.8%) responded to the treatment with melatonin. Gender and age (children younger and older than 12 years) did not affect the response to melatonin on sleep. Patients with or without comorbidities did not differ according to sleep response. Specific comorbidities with disruptive behavior disorders (oppositional defiant disorder or conduct disorder), affective (mood and anxiety) disorders and learning disabilities did not affect the efficacy of melatonin on sleep. Treatment was well tolerated, and no side effects related to melatonin were reported.ConclusionIn children with ADHD with sleep problems after receiving MPH treatment, melatonin may be an effective and safe treatment, irrespective of gender, age and comorbidities.

Real-world effectiveness of antipsychotic monotherapy and polytherapy in 1543 patients with acute-phase schizophrenia.

The effectiveness of antipsychotic treatments in the acute phase of schizophrenia in actual clinical practice remains somewhat unclear. Therefore, the purpose of the present naturalistic, multi-center study conducted from 1 year starting in September 2017 was to examine the response rate to an initial or second antipsychotic in newly admitted patients with acute-phase schizophrenia, as well as the response rate and quality of augmentation with two antipsychotics in patients who failed to respond to both the initial and second antipsychotics. In total, there were 660 (42.8%) and 243 (15.7%) responders to an initial and a second antipsychotic, respectively; thus, 58.5% of all patients were responders to an initial or second antipsychotic. Among 581 nonresponders (37.7%), the initial antipsychotic or a third antipsychotic was added to the second antipsychotic. Among these patients, 89.8% showed a Clinical Global Impression-Improvement score ≤3 (from 'minimally improved' to 'very much improved'). The rates of adverse events such as hyperglycemia, hyper-low-density lipoprotein cholesterolemia, hypertriglyceridemia, hyperprolactinemia, QTc prolongation, and extrapyramidal symptoms were not high in patients receiving augmentation with two antipsychotics compared with all patients, and no serious adverse events were reported. Antipsychotic augmentation may be an option in acute-phase treatment for patients who do not respond to either an initial or a second antipsychotic.

Lithium Treatment Is Safe in Children With Intellectual Disability.

Lithium is a widely used and effective treatment for individuals with psycho-neurological disorders, and it exhibits protective and regenerative properties in multiple brain injury animal models, but the clinical experience in young children is limited due to potential toxicity. As an interim analysis, this paper reports the safety/tolerability profiles of low-dose lithium treatment in children with intellectual disability (ID) and its possible beneficial effects. In a randomized, single-center clinical trial, 124 children with ID were given either oral lithium carbonate 6 mg/kg twice per day or the same dose of calcium carbonate as a placebo (n = 62/group) for 3 months. The safety of low-dose lithium treatment in children, and all the adverse events were monitored. The effects of low-dose lithium on cognition was evaluated by intelligence quotient (IQ), adaptive capacity was assessed by the Infant-Junior Middle School Students Social-Life Abilities Scale (IJMSSSLAS), and overall performance was evaluated according to the Clinical Global Impression-Improvement (CGI-I) scale. After 3 months of lithium treatment, 13/61 children (21.3%) presented with mild side effects, including 4 (6.6%) with gastrointestinal symptoms, 4 (6.6%) with neurological symptoms, 2 (3.3%) with polyuria, and 3 (4.9%) with other symptoms—one with hyperhidrosis, one with alopecia, and one with drooling. Four children in the lithium group had elevated blood thyroid stimulating hormone, which normalized spontaneously after lithium discontinuation. Both IQ and IJMSSSAS scores increased following 3 months of lithium treatment (F = 11.03, p = 0.002 and F = 7.80, p = 0.007, respectively), but such increases were not seen in the placebo group. CGI-I scores in the lithium group were 1.25 points lower (better) than in the placebo group (F = 82.66, p < 0.001) after 3 months of treatment. In summary, lithium treatment for 3 months had only mild and reversible side effects and had positive effects on cognition and overall performance in children with ID.Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR-IPR-15007518.

A Retrospective Chart Review of Buspirone for the Treatment of Anxiety in Psychiatrically Referred Youth with High-Functioning Autism Spectrum Disorder.

Anxiety disorders (ADs) are commonly associated with high-functioning Autism Spectrum Disorder (HF-ASD) and often worsen with age. Buspirone is a commonly prescribed anxiolytic drug with a favorable tolerability profile that may offer potential benefits in anxiety management for patients with HF-ASD. This study examines inadequately explored tolerability and effectiveness of buspirone in treating ADs comorbid with high-functioning ASD. A retrospective chart review of a 1-year period was conducted in psychiatrically referred population of HF-ASD youth with AD (age 8-17 years) who were treated with buspirone (N = 31). Information on the demographics and treatment history was recorded. Effectiveness was assessed through the Clinical Global Impressions Scale (CGI) severity (CGI-S) and improvement (CGI-I) scores noted by the treating clinician. A total of 31 patients were prescribed buspirone during the determined period, at a mean dose of 41.61 ± 24.10 mg for an average duration of 272 ± 125 days. Change in the CGI-S mean scores with treatment suggests an overall improvement in the severity of anxiety symptoms (MT1 = 4.9 ± 0.7; MT2 = 2.8 ± 0.87; p < 0.001). Significant improvement in anxiety symptoms (CGI-I ≤ 2) was observed in 58% and mild improvement (CGI-I = 3) in 29% of the HF-ASD patients who received buspirone treatment. Buspirone was well tolerated with no adverse events reported by the majority of participants, with the exception of two subjects who developed treatment emergent adverse events (activation and mood lability). Findings from this retrospective chart review suggest a promising role of buspirone in managing anxiety among youth with HF-ASD. Further research with prospective and randomized-controlled trials is necessary.

Safety and efficacy of self-administered inhaled loxapine (ADASUVE) in agitated patients outside the hospital setting: protocol for a phase IV, single-arm, open-label trial

IntroductionThere is a need for fast-acting, non-injection antiagitation treatments that are well tolerated and can be used outside of healthcare facilities. In phase II/III trials, an inhaled formulation of loxapine...

Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis: an open-label, long-term, Phase III extension study

PurposeTo assess long-term safety, tolerability, and efficacy of duloxetine in Japanese patients with chronic knee pain due to osteoarthritis.MethodsIn this open-label extension study (NCT02335346), Japanese patients with knee osteoarthritis and pain (Brief Pain Inventory [BPI] – Severity average pain score ≥4 at start of randomized trial) who had previously received duloxetine 60 mg/day or placebo for 14 weeks in a double-blind randomized trial entered the extension and received duloxetine 60 mg/day for 48 weeks. The primary outcome was safety/tolerability, secondary outcomes were change in BPI-Severity (BPI-S) average pain, BPI-Interference (BPI-I), Patient Global Impression-Improvement (PGI-I), Clinical Global Impression-Improvement (CGI-I), 36-item Short-Form Health Survey (SF36), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and exploratory outcomes were knee range of motion (efficacy outcome) and Kellgren–Lawrence grade (safety outcome).ResultsOf 323 patients who completed the randomized trial, 93 (50 placebo, 43 duloxetine) entered the extension. Most patients (85, 91.4%) experienced an adverse event, most commonly constipation, nasopharyngitis, somnolence, and dry mouth (≥10% of patients). There were eight serious adverse events in seven patients and no deaths. No obvious duloxetine-related changes were observed in laboratory tests, vital signs, or electrocardiograms. The change from baseline in BPI-S average pain score was significant throughout the extension. Significant reductions in BPI-I, PGI-I, CGI-I, WOMAC, and SF36 scores were also maintained through 52 weeks. There were no substantial changes in range of motion or Kellgren–Lawrence grade.ConclusionIn Japanese patients with chronic knee pain due to osteoarthritis, long-term treatment with duloxetine was well tolerated and associated with sustained improvements in pain and health-related quality of life without radiographic deterioration.

When Can We Predict the Outcome of an Electroconvulsive Therapy Course in Adolescents?: A Retrospective Study.

There is a dearth of up-to-date literature regarding electroconvulsive therapy (ECT) in adolescents, and the question of when to pronounce course failure has not been properly addressed. The current study aims to evaluate trajectories of clinical status throughout ECT courses in adolescent patients. We retrieved detailed data of 36 patients who received ECT in our treatment center. Clinical records were retrospectively assessed and evaluated every 6 ECT sessions to quantify Clinical Global Impressions-Improvement (CGI-I) scores. The mean number of sessions per course was 24.4 ± 14.2. The mean CGI-I score at the conclusion of the ECT courses was 2.47 ± 1.19. At the end of the acute treatment stage, 26 patients (72.2%) were much or very much improved, based on CGI-I scores. Only 5 patients exhibited a significant response after 6 sessions or fewer, whereas 21 patients (56.6%) improved after 12 sessions. Pearson correlations between CGI-I scores throughout the course of ECT showed no significant correlation between CGI-I scores after 6 sessions and the final CGI-I scores. However, a significant correlation was found between CGI-I scores after 12 sessions and the final CGI-I score. An improvement in the clinical status of adolescents treated by ECT might occur only after a substantial number of sessions. An early lack of response does not necessarily predict a failed ECT course.