Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 385
Filtrar
1.
Lancet Digit Health ; 2(4): e168-e178, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-33334505

RESUMO

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a common paediatric neurodevelopmental disorder with substantial effect on families and society. Alternatives to traditional care, including novel digital therapeutics, have shown promise to remediate cognitive deficits associated with this disorder and may address barriers to standard therapies, such as pharmacological interventions and behavioural therapy. AKL-T01 is an investigational digital therapeutic designed to target attention and cognitive control delivered through a video game-like interface via at-home play for 25 min per day, 5 days per week for 4 weeks. This study aimed to assess whether AKL-T01 improved attentional performance in paediatric patients with ADHD. METHODS: The Software Treatment for Actively Reducing Severity of ADHD (STARS-ADHD) was a randomised, double-blind, parallel-group, controlled trial of paediatric patients (aged 8-12 years, without disorder-related medications) with confirmed ADHD and Test of Variables of Attention (TOVA) Attention Performance Index (API) scores of -1·8 and below done by 20 research institutions in the USA. Patients were randomly assigned 1:1 to AKL-T01 or a digital control intervention. The primary outcome was mean change in TOVA API from pre-intervention to post-intervention. Safety, tolerability, and compliance were also assessed. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02674633 and is completed. FINDINGS: Between July 15, 2016, and Nov 30, 2017, 857 patients were evaluated and 348 were randomly assigned to receive AKL-T01 or control. Among patients who received AKL-T01 (n=180 [52%]; mean [SD] age, 9·7 [1·3] years) or control (n=168 [48%]; mean [SD] age, 9·6 [1·3] years), the non-parametric estimate of the population median change from baseline TOVA API was 0·88 (95% CI 0·24-1·49; p=0·0060). The mean (SD) change from baseline on the TOVA API was 0·93 (3·15) in the AKL-T01 group and 0·03 (3·16) in the control group. There were no serious adverse events or discontinuations. Treatment-related adverse events were mild and included frustration (5 [3%] of 180) and headache (3 [2%] of 180). Patient compliance was a mean of 83 (83%) of 100 expected sessions played (SD, 29·2 sessions). INTERPRETATION: Although future research is needed for this digital intervention, this study provides evidence that AKL-T01 might be used to improve objectively measured inattention in paediatric patients with ADHD, while presenting minimal adverse events. FUNDING: Sponsored by Akili Interactive Labs.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Atenção , Terapia Comportamental/métodos , Cognição , Software , Jogos de Vídeo , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Pediatria , Jogos e Brinquedos , Índice de Gravidade de Doença
2.
CNS Spectr ; : 1-11, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33077012

RESUMO

BACKGROUND: Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia. METHODS: Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score. RESULTS: About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of -15.6 at week 52 and -18.4 at week 104. CONCLUSION: In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33038454

RESUMO

OBJECTIVE: Risk calculators (RC) to predict clinical outcomes are gaining interest. A RC to estimate risk of bipolar spectrum disorders (BPSD) could help reduce the duration of undiagnosed BPSD and improve outcomes. Our objective was to adapt a RC previously validated in the Pittsburgh Bipolar Offspring study sample (BIOS; Hafeman et al., 2017) to achieve adequate predictive ability in both familial high risk and clinical high risk youth. METHOD: Participants (aged 6-12 at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study (N=473) were evaluated semi-annually. Evaluations included a KSADS interview. After testing a RC that closely approximated the original, we made modifications to improve model prediction. Models were trained in the BIOS sample and tested in LAMS. The final model was then trained in LAMS participants, including family history of BPSD as a predictor, and tested in the familial high-risk sample. RESULTS: Over follow-up, 65 youth newly met criteria for BPSD. The original RC identified youth who developed BPSD only moderately well (AUC = 0.67). Eliminating predictors other than the KSADS screening items for mania and depression improved accuracy (AUC=0.73) and generalizability. The model trained in LAMS, including family history as a predictor, performed well in the BIOS sample (AUC=0.74). CONCLUSION: The clinical circumstances under which the assessment of symptoms occurs impacts RC accuracy; focusing on symptoms related to the onset of BPSD improved generalizability. Validation of the RC under clinically-realistic circumstances will be an important next step.

4.
Clin Ther ; 42(8): 1452-1466, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32723670

RESUMO

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

5.
J Atten Disord ; : 1087054720943283, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32697138

RESUMO

Objective: The purpose of the present study was to characterize prescription stimulant non-medical use (NMU) in adolescents between the ages of 13 and 18 years seeking treatment for substance use disorder (SUD) with the Comprehensive Health Assessment Tool for Teens (CHAT™). Method: Adolescents being evaluated for SUD treatment between Q1 2010 and Q3 2017 (n = 20,189) completed the CHAT™. Results: About 4.3% of the sample (N = 867) of adolescents in SUD treatment reported past 30-day prescription stimulant NMU. Compared to those without past 30-day prescription stimulant NMU, more reported a lifetime diagnosis of learning disorder or ADHD, more took medication for emotional, behavioral, or learning disorders, received past-month inpatient treatment, or were currently not enrolled in school. Prescription stimulants were most often taken orally for NMU, however, approximately half reported using alternate routes of administration, the most prominent of which was intranasal use. Conclusion: About 4.3% of adolescents in SUD treatment evaluation reported past 30-day prescription stimulant NMU. Greater percentages of lifetime learning disorder, medication use, past-month inpatient treatment, school unenrollment, and overall substance misuse were associated with prescription stimulant NMU, as were alternate routes of administration. These data reveal an ongoing, persistent level of past-30-day NMU of prescription stimulants among adolescents being evaluated for SUD treatment.

6.
J Affect Disord ; 272: 508-520, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32553395

RESUMO

BACKGROUND: Despite the well-documented negative impact of untreated bipolar illness, approaches to early intervention in childhood-onset bipolar and related disorders are not well delineated. METHODS: We reviewed the extant treatment literature on children at high risk for bipolar disorder, with definitions based on family history, childhood adversity, and prodromal symptoms. RESULTS: A panoply of approaches have been described, but most interventions are based on an inadequate database to support their routine implementation. We classify early stage interventions as a function of their safety and tolerability with the hope that these might generate more rigorous study and a stronger database. LIMITATIONS: Critics may rightly argue that identifying viable treatment methods is premature given our lack of ability to reliably predict illness trajectory in very young children. However, many of the psychosocial and pharmacological interventions we present could have nonspecific positive effects across a variety of symptoms, syndromes, and diagnoses, further enhancing the rationale for more rigorous study. CONCLUSIONS: Early stage interventions have the potential to improve functioning in prodromal illness and exert long-term positive effects on the course of illness. Many of the safest interventions deserve consideration for implementation and dissemination studies.

7.
J Dev Behav Pediatr ; 41(5): 349-358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555070

RESUMO

OBJECTIVE: Previous studies of Tai Chi or mindfulness-based interventions in attention-deficit/hyperactivity disorder (ADHD) have relied on self- or parent-reported outcome measures; however, there is a critical need for the validation of objective biomarkers of treatment. Therefore, we implemented a mindful movement intervention for children with ADHD, hypothesizing that an ADHD-relevant motor control measure could serve as a predictive biomarker of treatment-related improvement. METHODS: Thirty-four participants were included, 8 to 12 year olds diagnosed with DSM-5 ADHD. Participants engaged in the mindful movement treatment, an 8-week program with 2 classes a week for 60 minutes. At pre- and post-treatment, ADHD symptoms and associated impairment and motor control via the Physical and Neurological Examination for Subtle Signs (PANESS) were assessed. RESULTS: The results showed a significant reduction for PANESS Gaits and Station (p ≤ 0.001), total overflow (p = 0.009), and total score (p = 0.001) after treatment, with the largest effect for Gaits and Stations. The results also showed a significant reduction in symptoms of inattention (p ≤ 0.001), hyperactivity/impulsivity (p ≤ 0.001), oppositional defiant disorder (p = 0.001), and executive dysfunction (p ≤ 0.001). There were significant positive correlations between change in PANESS Gaits and Stations and change in both inattentive (p = 0.02) and hyperactive/impulsive symptoms (p = 0.02). There was also a significant positive correlation between change in the PANESS total score and change in inattentive (p = 0.007) and hyperactive/impulsive symptoms (p = 0.042). The change in the PANESS total score (ß = 0.295, p = 0.002) predicted post-treatment ADHD severity above the change in inattentive or hyperactive/impulsive symptoms. CONCLUSION: The results suggest the effectiveness of a mindful movement treatment on ADHD symptoms and suggest the PANESS as a candidate motor biomarker for future mindful movement trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02234557, https://clinicaltrials.gov/ct2/show/NCT02234557.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32556647

RESUMO

Describe hospitalization rates in children with elevated symptoms of mania and determine predictors of psychiatric hospitalizations during the 96 month follow-up. Eligible 6-12.9 year olds and their parents visiting 9 outpatient mental health clinics were invited to be screened with the Parent General Behavior Inventory 10-item Mania Scale. Of 605 children with elevated symptoms of mania eligible for follow-up, 538 (88.9%) had ≥ 1 of 16 possible follow-up interviews and are examined herein. Multivariate Cox regression indicated only four factors predicted hospitalizations: parental mental health problems (HR 1.80; 95% CI 1.21, 2.69); hospitalization prior to study entry (HR 3.03; 95% CI 1.80, 4.43); continuous outpatient mental health service use (HR 3.73; 95% CI 2.40, 5.50); and low parental assessment of how well treatment matched child's needs (HR 3.97; 95% CI 2.50, 6.31). Parental perspectives on mental health services should be gathered routinely, as they can signal treatment failures.

9.
J Affect Disord ; 273: 146-156, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32421595

RESUMO

BACKGROUND: The affective go/no-go (AGN) task has been used to assess affective biases in attention set-shifting and deficits in inhibitory control of emotional information among depressed youth, but results have been inconsistent. We aimed to test AGN robustness and clarify temporal relationships between depressive symptoms and affective processing in youth. METHODS: We evaluated AGN performance twice (Time 1 N = 306; Time 2 N = 238) in relation to current, previous, and future depression in the same children/adolescents with depression and those without diagnoses who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Mixed repeated ANCOVAs were powered to detect small-medium group by valence interactions in response latency and errors. Supplemental regression analyses examined depressive symptoms as a continuous variable in relation to AGN performance. RESULTS: No clear pattern emerged, mirroring the broader AGN literature. In primary analyses, group by valence interactions were only observed at one AGN administration; none replicated across administrations. Similarly, in regression analyses depressive symptoms had no relation to affective processing biases/deficits at AGN Time 1, though some relationships were detected between symptoms and AGN Time 2. LIMITATIONS: Relatively few youth met criteria for a depressive disorder, though analyses were appropriately powered and supplemental analyses examined depressive symptoms continuously. Comparison groups were not healthy controls at recruitment but were free from any Axis I disorder at AGN administration. CONCLUSIONS: Given the inconsistency of AGN findings, attention should be focused on tasks that provide more sensitive, robust measures of emotional information processing in depressed youth.

10.
J Clin Child Adolesc Psychol ; : 1-17, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32401546

RESUMO

Objective: To evaluate short forms of free self-report mania and depression scales, evaluating their reliability, content coverage, criterion validity, and diagnostic accuracy.Method: Youths age 11 to 18 years seeking outpatient mental health services at either an Academic medical clinic (N = 427) or urban Community mental health center (N = 313), completed the General Behavior Inventory (GBI) and other rating scales. Youths and caregivers completed semi-structured interviews to establish diagnoses and mood symptom severity, with GBI scores masked during diagnosis. Ten- and seven-item short forms, psychometric projections, and observed performance were tested first in the Academic sample and then externally cross-validated in the Community sample.Results: All short forms maintained high reliability (all alphas >.80 across both samples), high correlations with the full-length scales (r.85 to.96), excellent convergent and discriminant validity with mood, behavior, and demographic criteria, and diagnostic accuracy undiminished compared to using the full-length scales. Ten-item scales showed advantages in terms of coverage; the 7 Up showed slightly weaker performance.Conclusions: Present analyses evaluated and externally cross-validated short forms that maintain high reliability and content coverage, and show strong criterion validity and diagnostic accuracy - even when used in an independent sample with very different demographics and referral patterns. The short forms appear useful in clinical applications including initial evaluation, as well as in research settings where they offer an inexpensive quantitative score. Short forms are available in more than two dozen languages. Future work should further evaluate sensitivity to treatment effects and cultural invariance.

11.
J Child Adolesc Psychopharmacol ; 30(6): 355-365, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32460523

RESUMO

Objective: To evaluate the efficacy and long-term safety of vilazodone in children and adolescent outpatients with major depressive disorder (MDD). Methods: Children and adolescents aged 7-17 years of age with MDD were randomized 2:2:1 to 8 weeks of double-blind placebo, vilazodone 15 or 30 mg/day or fluoxetine 20 mg/day, respectively. The primary and secondary efficacy outcomes, respectively, were change from baseline to week 8 in Children's Depression Rating Scale-Revised (CDRS-R) score total score and Clinical Global Impressions-Severity (CGI-S) score analyzed using a mixed model for repeated measurement approach. Patients who completed the 8-week randomized controlled trial (RCT), as well as new (de novo) patients, could participate in a 26-week, vilazodone-only, open-label extension (OLE) study. Results: The RCT enrolled 473 patients (60% female) with an average age of 13 years. Change in CDRS-R and CGI-S scores from baseline to week 8 did not differ between patients who received vilazodone and those randomized to placebo. The least-squares mean change from baseline in CDRS-R scores was similar for vilazodone and placebo (-20.7 vs. -20.3, p = 0.77; least-squares mean difference [LSMD] = -0.40). For fluoxetine, the LSMD versus placebo was -2.3 (p = 0.14). The OLE enrolled 330 patients (60% female) with an average age of 13-14 years. Overall, no new safety concerns were identified compared to what is known in adults. Conclusions: Similar improvements in depressive symptoms were observed in all arms. This study does not support the efficacy of vilazodone 15 or 30 mg/day for pediatric patients with MDD. No new or unexpected safety concerns were detected during the RCT or OLE studies.

12.
CNS Spectr ; : 1-9, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32228725

RESUMO

Impulsive aggressive (IA, or impulsive aggression) behavior describes an aggregate set of maladaptive, aggressive behaviors occurring across multiple neuropsychiatric disorders. IA is reactive, eruptive, sudden, and unplanned; it provides information about the severity, but not the nature, of its associated primary disorder. IA in children and adolescents is of serious clinical concern for patients, families, and physicians, given the detrimental impact pediatric IA can have on development. Currently, the ability to properly identify, monitor, and treat IA behavior across clinical populations is hindered by two major roadblocks: (1) the lack of an assessment tool designed for and sensitive to the set of behaviors comprising IA, and (2) the absence of a treatment indicated for IA symptomatology. In this review, we discuss the clinical gaps in the approach to monitoring and treating IA behavior, and highlight emerging solutions that may improve clinical outcomes in patients with IA.

13.
J Child Adolesc Psychopharmacol ; 30(3): 128-136, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32233956

RESUMO

Objectives: Describe the safety and tolerability of lisdexamfetamine dimesylate (LDX) and provide data on clinical effects for efficacy-related endpoints and pharmacokinetics in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD). Methods: This phase 2, multicenter, open-label, dose-optimization study (ClinicalTrials.gov registry: NCT02402166) was conducted at seven U.S. sites between April 15, 2015, and June 30, 2016. Children (4-5 years of age) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for ADHD and having ADHD Rating Scale-IV Preschool version (ADHD-RS-IV-PS) total scores ≥28 (boys) or ≥24 (girls) were eligible. Open-label LDX (8-week duration) was initiated at 5 mg and titrated to 30 mg until achieving an optimal dose. Assessments included treatment-emergent adverse events (TEAEs), vital sign changes, ADHD-RS-IV-PS total score changes, and pharmacokinetic evaluations. Results: Among 24 participants, the most frequently reported TEAE was decreased appetite (8/24; 33%). At week 8/early termination, mean (standard deviation) systolic and diastolic blood pressure and pulse changes from baseline were -1.1 (7.31) and 1.5 (6.93) mmHg and -0.8 (12.75) bpm, respectively. The mean (95% confidence interval) change from baseline ADHD-RS-IV-PS total score at the final on-treatment assessment was -26.1 (-32.2 to -20.0). Pharmacokinetic parameters of d-amphetamine, a major active metabolite of LDX, were characterized: d-amphetamine exposure increased with LDX dose; mean tmax and t1/2, respectively, ranged from 4.00 to 4.23 hours and 7.18 to 8.46 hours. Conclusions: In preschool-aged children with ADHD, LDX was generally well tolerated and reduced ADHD symptoms, consistent with observations in children 6-17 years of age. Based on these findings, a starting LDX dose as low as 5 mg in phase 3 studies in preschool-aged children is supported.

14.
J Atten Disord ; : 1087054720909084, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32338106

RESUMO

Objective: To evaluate efficacy and safety of SPN-810 (extended-release molindone) in a Phase-2b, randomized, double-blind, placebo-controlled, dose-ranging study of children (6-12 years) with ADHD and persistent impulsive aggression (IA). Method: After lead-in, children were randomized to (a) placebo (N = 31); (b) low-dose (N = 29, 12/18 mg/day); (c) medium-dose (N = 30, 24/36 mg/day); and (4) high-dose (N = 31, 36/54 mg/day) groups. Treatment included ~2.5-week titration, 3-week maintenance, and 1-week tapering/conversion, alongside existing monotherapy (stimulants/nonstimulants) and behavioral therapy. The primary endpoint was change in Retrospective-Modified Overt Aggression Scale (R-MOAS) score at end of study, with safety monitored. Results: A total of 95 (78.5%) children completed the study. Aggression (R-MOAS) improved with low and medium doses (low dose: p = .031; medium dose: p = .024; high dose: p = .740). The most common adverse events were headache (10.0%), sedation (8.9%), and increased appetite (7.8%). Conclusion: These results suggest SPN-810 may be effective in reducing residual IA behaviors in children with ADHD. Research is still needed to support the benefit-risk profile of SPN-810 in pediatric populations.

15.
J Child Adolesc Psychopharmacol ; 30(3): 166-172, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32101469

RESUMO

Objective: Study goals were to (1) provide a rationale for developing a composite primary outcome score that includes symptom severity for attention-deficit/hyperactivity disorder (ADHD) and emotional dysregulation, plus symptom-induced impairment; (2) demonstrate weighting methods to calculate the composite score using a sample of children diagnosed with ADHD and aggression; and (3) identify the optimal weighting method most sensitive to change, as measured by effect sizes. Methods: We conducted secondary data analyses from the previously conducted Treatment of Severe Childhood Aggression (TOSCA) study. Children aged 6-12 years were recruited through academic medical centers or community referrals. The composite primary outcome comprised the ADHD, oppositional defiant disorder, disruptive mood dysregulation disorder, and peer conflict subscales from the Child and Adolescent Symptom Inventory (CASI), a DSM (Diagnostic and Statistical Manual)-referenced rating scale of symptom severity and symptom-induced impairment. Five weighting methods were tested based on input from senior statisticians. Results: The composite score demonstrated a larger (Cohen's d) effect size than the individual CASI subscales, irrespective of the weighting method (10%-55% larger). Across all weighting methods, effect sizes were similar and substantial: approximately a two-standard deviation symptom reduction (range: -1.97 to -2.04), highest for equal item and equal subscale weighting, was demonstrated, from baseline to week 9, among all TOSCA participants. The composite score showed a medium positive correlation with the Clinical Global Impressions-Severity scores, 0.46-0.47 for all weighting methods. Conclusions: A composite score that included severity and impairment ratings of ADHD and emotional dysregulation demonstrated a more robust pre-post change than individual subscales. This composite may be a more useful indicator of clinically relevant improvement in heterogeneous samples with ADHD than single subscales, avoiding some of the statistical limitations associated with multiple comparisons. Among the five similar weighting methods, the two best appear to be the equal item and equal subscale weighting methods.

16.
Neurology ; 94(9): 392-404, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32051244

RESUMO

OBJECTIVE: To review pharmacologic and nonpharmacologic strategies for treating sleep disturbances in children and adolescents with autism spectrum disorder (ASD) and to develop recommendations for addressing sleep disturbance in this population. METHODS: The guideline panel followed the American Academy of Neurology 2011 guideline development process, as amended. The systematic review included studies through December 2017. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS LEVEL B: For children and adolescents with ASD and sleep disturbance, clinicians should assess for medications and coexisting conditions that could contribute to the sleep disturbance and should address identified issues. Clinicians should counsel parents regarding strategies for improved sleep habits with behavioral strategies as a first-line treatment approach for sleep disturbance either alone or in combination with pharmacologic or nutraceutical approaches. Clinicians should offer melatonin if behavioral strategies have not been helpful and contributing coexisting conditions and use of concomitant medications have been addressed, starting with a low dose. Clinicians should recommend using pharmaceutical-grade melatonin if available. Clinicians should counsel children, adolescents, and parents regarding potential adverse effects of melatonin use and the lack of long-term safety data. Clinicians should counsel that there is currently no evidence to support the routine use of weighted blankets or specialized mattress technology for improving disrupted sleep. If asked about weighted blankets, clinicians should counsel that the trial reported no serious adverse events with blanket use and that blankets could be a reasonable nonpharmacologic approach for some individuals.


Assuntos
Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/terapia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/terapia , Adolescente , Transtorno do Espectro Autista/complicações , Criança , Humanos , Distúrbios do Início e da Manutenção do Sono/complicações
17.
Artigo em Inglês | MEDLINE | ID: mdl-31982581

RESUMO

OBJECTIVE: A recent 3-month double-blind, placebo-controlled study demonstrated efficacy and safety of pediatric prolonged-release melatonin (PedPRM) for insomnia in children with autism spectrum disorder. This study examined the long-term effects of PedPRM treatment on sleep, growth, body mass index, and pubertal development. METHOD: Eighty children and adolescents (2-17.5 years of age; 96% with autism spectrum disorder) who completed the double-blind, placebo-controlled trial were given 2 mg, 5 mg, or 10 mg PedPRM nightly up to 104 weeks, followed by a 2-week placebo period to assess withdrawal effects. RESULTS: Improvements in child sleep disturbance and caregiver satisfaction with child sleep patterns, quality of sleep, and quality of life were maintained throughout the 104-week treatment period (p < .001 versus baseline for all). During the 2-week withdrawal placebo period, measures declined compared with the treatment period but were still improved compared with baseline. PedPRM was generally safe; the most frequent treatment-related adverse events were fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%). Changes in mean weight, height, body mass index, and pubertal status (Tanner staging done by a physician) were within normal ranges for age with no evidence of delay in body mass index or pubertal development. CONCLUSION: Nightly PedPRM at optimal dose (2, 5, or 10 mg nightly) is safe and effective for long-term treatment in children and adolescents with autism spectrum disorder and insomnia. There were no observed detrimental effects on children's growth and pubertal development and no withdrawal or safety issues related to the use or discontinuation of the drug. CLINICAL TRIAL REGISTRATION INFORMATION: Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities; https://clinicaltrials.gov/; NCT01906866.

18.
J Child Psychol Psychiatry ; 61(2): 175-181, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31523819

RESUMO

OBJECTIVE: To examine development of bipolar spectrum disorders (BPSD) and other disorders in prospectively followed children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In the Longitudinal Assessment of Manic Symptoms (LAMS) study, 531 of 685 children age 6-12 (most selected for scores > 12 on General Behavior Inventory 10-item Mania scale) had ADHD, 112 with BPSD, and 419 without. With annual assessments for 8 years, retention averaged 6.2 years. Chi-square analyses compared rate of new BPSD and other comorbidity between those with versus without baseline ADHD and between retained versus resolved ADHD diagnosis. Cox regression tested factors influencing speed of BPSD onset. RESULTS: Of 419 with baseline ADHD but not BPSD, 52 (12.4%) developed BPSD, compared with 16 of 110 (14.5%) without either baseline diagnosis. Those who developed BPSD had more nonmood comorbidity over the follow-up than those who did not develop BPSD (p = .0001). Of 170 who still had ADHD at eight-year follow-up (and not baseline BPSD), 26 (15.3%) had developed BPSD, compared with 16 of 186 (8.6%) who had ADHD without BPSD at baseline but lost the ADHD diagnosis (χ2  = 3.82, p = .051). There was no statistical difference in whether ADHD persisted or not across new BPSD subtypes (χ2  = 1.62, p = .446). Of those who developed BPSD, speed of onset was not significantly related to baseline ADHD (p = .566), baseline anxiety (p = .121), baseline depression (p = .185), baseline disruptive behavior disorder (p = .184), age (B = -.11 p = .092), maternal mania (p = .389), or paternal mania (B = .73, p = .056). Those who started with both diagnoses had more severe symptoms/impairment than those with later developed BPSD and reported having ADHD first. CONCLUSIONS: In a cohort selected for symptoms of mania at age 6-12, baseline ADHD was not a significant prospective risk factor for developing BPSD. However, persistence of ADHD may marginally mediate risk of BPSD, and early comorbidity of both diagnoses increases severity/impairment.

19.
Handb Exp Pharmacol ; 261: 397-413, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31598836

RESUMO

Pharmacotherapy of psychiatric illnesses in children and adolescents has grown significantly over the last few decades. However, the body of research examining pharmacological treatments for psychiatric illnesses is much smaller in children and adolescents than it is in adults. As most treatments for psychiatric disorders are more effective if started early in the course of illness, treatment options for youth are especially important in order to ensure better treatment outcomes. This chapter discusses currently approved medications to treat psychiatric disorders in children and adolescents. Research on medications that may be effective treatments but are not yet FDA approved is also discussed. The medications are broken down into major categories used in youth with psychiatric disorders including antidepressants, mood stabilizers, ADHD medications, and antipsychotics.


Assuntos
Antipsicóticos , Transtornos Mentais , Adolescente , Adulto , Antidepressivos/farmacologia , Antimaníacos/farmacologia , Criança , Humanos
20.
J Clin Child Adolesc Psychol ; 49(6): 787-803, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31343896

RESUMO

The goal of this study is to develop a rational data-driven definition of impulsive/reactive aggression and establish distinctions between impulsive/reactive aggression and other common childhood problems. This is a secondary analysis of data from Assessing Bipolar: A Community Academic Blend (ABACAB; N = 636, ages 5-18), Stanley Medical Research Institute N = 392, ages 5-17), and the Longitudinal Assessment of Manic Symptoms (LAMS; N = 679, ages 6-12) studies, which recruited youths seeking outpatient mental health services in academic medical centers and community clinics. Following Jensen et al.'s (2007) procedure, 3 judges independently rated items from several widely used scales in terms of assessing impulsive/reactive aggression. Principal components analyses (PCA) modeled structure of the selected items supplemented by items related to mood symptoms, rule-breaking behavior, and hyperactivity/impulsivity to better define the boundaries between impulsive/reactive aggression and other common childhood symptoms. In the rational item selection process, there was good agreement among the 3 experts who rated items as characterizing impulsive/reactive aggression or not. PCA favored 5 dimension solutions in all 3 samples. Across all samples, PCA resulted in rule-breaking behavior, aggression-impulsive/reactive (AIR), mania, and depression dimensions; there was an additional hyperactive/impulsive dimension in the LAMS sample and a self-harm dimension in ABACAB and Stanley samples. The dimensions demonstrated good internal consistency; criterion validity coefficients also showed consistency across samples. This study is a step toward developing an empirically derived nosology of impulsive aggression/AIR. Findings support the validity of the AIR construct, which can be distinguished from manic and depressive symptoms as well as rule-breaking behavior.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA