Sleep in adults with Autism Spectrum Disorder: a systematic review and meta-analysis of subjective and objective studies.

BACKGROUND/OBJECTIVE: Sleep problems are commonly reported by individuals with Autism Spectrum Disorder (ASD). However, to date, no quantitative evidence synthesis of available studies has been performed to quantify sleep alterations in adults with ASD. We performed a systematic review and meta-analysis of objective (ie, based on actigraphy or polysomnography [PSG]) and subjective (ie, based on sleep diaries/questionnaires) studies comparing sleep parameters in adults with ASD and in a typically developing (TD) control group. METHODS: PubMed, OVID databases and Web of Knowledge were systematically searched up to February 2019 with no language restrictions. Original studies including adults with a diagnosis of ASD according to DSM, ICD, or based on standard diagnostic tools (eg, ADOS), and a TD control group were included. Random-effects models were used. Study quality was evaluated with the Newcastle Ottawa Scale (NOS). Analyses were conducted using Comprehensive Meta-Analysis. RESULTS: From initial pool of 1948 references, 14 publications including 8 datasets, (194 ASD and 277 controls) met the inclusion criteria. Compared to controls, individuals with ASD were significantly more impaired in six out of 11 subjective parameters, including lower sleep efficiency (SE, SMD = -0.87, CI = -1.14 - 0.60) and in 10 out of 17 objective outcomes, including longer sleep onset latency (PSG) (SMD = 0.86, CI = 0.29-1.07) and wake after sleep onset (WASO, actigraphy) (SMD = 0.57, CI = 0.28-0.87). The mean NOS score was 4.88/6. CONCLUSIONS: Individuals with ASD demonstrated impaired sleep compared to controls in most subjective and objective measures.

Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD.

Introduction: Despite stimulants being highly efficacious in short-term randomized controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of novel non-stimulant options are currently in the pipeline for the treatment of attention-deficit/hyperactivity disorder (ADHD). Areas covered: The authors conducted a systematic review of RCTs registered in ClinicalTrials.gov in the past 5 years (January 2014 and February 2019), supplemented by searches in PubMed, Web of Science, and drug manufacturer websites to find recent RCTs on novel non-stimulant ADHD medications. Expert opinion: The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), Mazindol, and Molindone hydrochloride (SPN-810). Given the high effect size found in RCTs of stimulants in terms of efficacy on ADHD core symptoms, it is unlikely that these novel agents will show better efficacy than stimulants, at the group level. However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a 'one size fits all' to a 'precision medicine' approach.

Inflammatory Cytokines in Children and Adolescents with Depressive Disorders: A Systematic Review and Meta-Analysis.

Objective: Meta-analytic evidence shows alterations of peripheral inflammatory cytokines in adults with depressive disorders. By contrast, no evidence synthesis on alterations of peripheral inflammatory cytokines in children/adolescents with depressive disorders is available to date. To fill this gap, we conducted a systematic review and meta-analysis of case-control studies comparing serum cytokine levels in children/adolescents with depressive disorders and healthy controls. Methods: Based on a preregistered protocol (PROSPERO-CRD42018095418), we searched PubMed, Ovid, and Web of Knowledge from inception through July 21, 2018, with no language restrictions, and contacted study authors for unpublished data/information. Random-effects model was used to compute effect size for each cytokine. The Newcastle-Ottawa Scale was used to asses study bias. Results: From a pool of 4231 nonduplicate, potentially relevant references, 8 studies were retained for the qualitative synthesis and 5 for the meta-analysis. TNF-α was higher in participants with depressive disorders versus controls, falling short of statistical significance. Conclusions: Overall, due to the small number of studies, in contrast to the literature in adults, further evidence is needed to confirm possible inflammatory alterations associated with depression in youth.