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Orexin receptor antagonists for sleep disturbance in attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review

BackgroundSleep disturbance is among the commonest and most impairing comorbidities of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Melatonin has the strongest evidence base, but its action is chronobiotic, its maintenance effect inconsistent, and adult evidence sparse. Orexin receptor antagonists reduce wake drive rather than induce sedation, a mechanistically distinct alternative.MethodsReported in accordance with PRISMA 2020. PubMed, Europe PMC, OpenAlex and ClinicalTrials.gov were searched on 23 September 2026 using three complementary concept searches with backward citation tracking; Embase and PsycINFO were not searched. Screening applied a mechanical rule, and every candidate was assessed at full text by two independent reviewers. Eligible reports described a person with diagnosed ADHD or ASD given an orexin receptor antagonist, with a sleep, behavioural, cognitive or safety outcome. Risk of bias was appraised at domain level and certainty against the GRADE domains without categorical ratings. Pooling was precluded by heterogeneity and by the absence of comparable controlled effect estimates.ResultsEight reports representing seven patient groups described 41 exposed participants, 25 with ADHD and 16 with ASD. No completed trial provides peer-reviewed or registry-posted diagnosis-specific outcomes. The strongest signal is a one-month open-label study of daridorexant 50 mg in 24 adults with ADHD and insomnia, where median insomnia severity fell from 16 to 8 and actigraphic total sleep time rose by about 24 minutes, both surviving correction, and 62.5% responded; no cognitive outcome survived correction, one worsened, and the favourable attention results required excluding sleep non-responders. In ASD the evidence is case reports and small series confounded by co-medication, the only comparison-group report being null. No report provides ADHD-stratified paediatric outcomes. Of two registered trials one is recruiting and one completed, the latter’s sponsor releasing top-line data without diagnosis-stratified outcomes.ConclusionOrexin receptor antagonism is a mechanistically coherent approach to sleep disturbance in ADHD and ASD, but no appraisable, diagnosis-specific controlled evidence supports its use, and the evidence is too sparse and biased for causal inference. The signal that sleep gains may accompany attention gains requires a randomised test. Routine use cannot be recommended, and off-label prescribing requires individualised specialist assessment.
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Temporal and demographic trends in deaths with co-recorded depressive disorders and digestive system diseases among U.S. adults: a 26-year nationwide analysis (1999–2024)

BackgroundDepression and digestive diseases are common public health concerns and may coexist through shared clinical and behavioral pathways. However, national mortality trends involving both conditions remain insufficiently characterized. This study examined temporal and demographic trends in deaths with co-recorded depressive disorders and digestive diseases among U.S. adults from 1999 to 2024.MethodsThis population-based retrospective cross-sectional study used the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death database. Deaths among adults aged ≥15 years were included when both depressive disorders (ICD-10 F32/F33) and digestive diseases (ICD-10 K00–K92) were recorded on death certificates. Crude mortality rates and age-adjusted mortality rates (AAMRs) were calculated per 100,000 population. Temporal trends were assessed using Joinpoint regression, and analyses were stratified by demographic and geographic characteristics. Disease-specific temporal trends were additionally evaluated for major digestive disease categories.ResultsFrom 1999 to 2024, 51,693 deaths with co-recorded depressive disorders and digestive diseases were identified. Annual deaths increased from 1,269 to 3,268, and the AAMR increased from 0.61 to 0.95 per 100,000 population. Joinpoint analysis identified significant increases during 1999–2003 (APC, 3.70%), 2010–2017 (APC, 2.51%), and 2017–2021 (APC, 10.94%), with declines during 2003–2010 (APC, −3.16%) and 2021–2024 (APC, −3.20%). Females had higher AAMRs than males, and older adults experienced the highest crude mortality rates. Mortality rates were higher among non-Hispanic White individuals and nonmetropolitan populations. The AAMR increased sharply during 2020–2021 and remained elevated in 2024 compared with the pre-pandemic level. Disease-specific analyses showed significant full-period increases for liver diseases (K70–K76; AAPC, 4.76%), gallbladder, biliary tract, and pancreatic diseases (K80–K86; AAPC, 3.04%), and esophageal, gastric, and duodenal diseases (K20–K31; AAPC, 2.48%).ConclusionsDeaths with co-recorded depressive disorders and digestive diseases increased among U.S. adults from 1999 to 2024, with substantial demographic, geographic, and disease-specific heterogeneity. These findings support integrated management of mental health and digestive diseases in high-risk populations. Because this study used aggregate death-certificate data and included only co-recorded cases, the findings describe mortality patterns rather than associations or causal relationships between depressive disorders and digestive diseases.
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Transcranial pulse stimulation in the treatment of cognitive disorders of aging: a systematic review

IntroductionNon-invasive brain stimulation techniques, specifically transcranial pulse stimulation (TPS) are of increasing interest due to their potential to fill in gaps left by current pharmacological treatments in cognitive disorders of aging. The current review’s aims were to systematically determine what cognitive disorders of aging have been studied with TPS as a treatment and to narratively summarize what is known about the effectiveness of TPS treatment in the aging subpopulation through neurocognitive performance metrics and neuroimaging metrics.MethodsThis review is PRISMA 2020 compliant. Searches were conducted in PubMed, PsycINFO (through PsycNET to include all APA Databases), Embase, and Scopus. Title/Abstract screening, full text screening, and extraction were completed by two independent reviewers with discrepancies worked out through discussion. Outcomes were systematically chosen for formal analysis where dual reviewers completed risk of bias and certainty of evidence assessments, and remaining outcomes were synthesized narratively.Results11 studies were included, consisting of 10 nonrandomized studies and 1 randomized controlled trial (RCT). Due to follow ups and suspected cohort overlap, the 11 studies are not representative of 11 independent patient cohorts. Included studies examined Alzheimer’s Disease and related dementias, mild neurocognitive disorder, mild cognitive impairment and Parkinson’s Disease through a variety of neurocognitive performance metrics and neuroimaging metrics. Formal synthesis showed a preliminary trend for positive change from before to after stimulation, particularly in neuropsychological batteries measuring global cognition, however number of contributing results and overall certainty of evidence were both very low. Neuroimaging results varied with trends of statistically significant functional changes, though also limited by limited literature and low certainty.DiscussionThough there is a continued need for high quality research and randomized controlled trials using TPS in the treatment of neurocognitive disorders of aging, the current evidence indicates potential for promising changes in neurocognitive performance metric outcomes and functional neuroimaging measures from before to after stimulation pending additional controlled trials. Though there is currently not enough high quality evidence to support clinical recommendations, what is known could support the use of TPS in the treatment of neurocognitive disorders of aging should RCTs continue to support positive improvements associated with this non-invasive intervention.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251246424.
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Dance-based exercise for healthy brain aging in older adults: integrating neuroplasticity, cognitive reserve, physical fitness, social engagement, and mental well-being

Population aging brings rising difficulties associated with cognitive deterioration, diminished physical capabilities, social isolation, and increased susceptibility to mental health problems. Finding accessible, multidomain approaches to promote healthy brain aging has become a major priority. Dance-based exercise is a distinctive form of physical activity that combines aerobic movement, motor coordination, cognitive involvement, social interaction, and emotional expression. Previous systematic reviews and meta-analyses have largely quantified isolated physical or cognitive outcomes following dance interventions. However, an accurate understanding of healthy brain aging requires synthesizing how these separate domains interact. This narrative review adds to the current literature by providing an integrated conceptual framework that connects the neurobiological, physical, and psychosocial dimensions of dance-based exercise. Rather than pooling isolated effect sizes, we examine theoretical mechanisms (e.g., task-specific neuroplasticity and cognitive reserve) that plausibly link multidomain elements of dance to brain aging; these mechanisms are primarily hypothesis-generating in the context of existing dance trials. This narrative review examines the potential mechanisms by which dance-based exercise may support healthy brain aging in older adults, emphasizing neuroplasticity, cognitive reserve, physical fitness, social participation, and psychological well-being. The evidence available indicates that dance-based interventions may be linked to gains in cognitive functioning, especially executive abilities and attention, along with improvements in balance, mobility, and functional performance. In addition, the social and enjoyable character of dance may help foster better psychological outcomes and emotional well-being, although current evidence specifically concerning loneliness remains mixed. However, differences across study designs, intervention protocols, participant characteristics, and outcome measures constrain the ability to draw definitive conclusions about causality and the most effective intervention parameters. New evidence suggests that dance-based exercise may offer a promising multidomain strategy for strengthening resilience and supporting brain health throughout aging. Further rigorously designed longitudinal studies and randomized controlled trials are required to elucidate the underlying mechanisms, determine which populations are most responsive, and develop evidence-based guidance for incorporating dance-based interventions into healthy aging and geriatric mental health approaches.
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Risk and protective factors for suicidality in older adults: an umbrella review and framework for multidimensional suicide risk assessment

IntroductionSuicidality in older adults is a major public health concern influenced by psychiatric, psychological, physical, functional, social, and socioeconomic factors. However, the evidence remains fragmented, and protective factors have received substantially less attention than risk factors.MethodsThis umbrella review followed JBI methodology and was reported in accordance with the PRISMA 2020 statement. PubMed, Scopus, and Web of Science were searched from inception to 30 June 2026 for systematic reviews and/or meta-analyses examining risk or protective factors for suicidal ideation, suicidal behavior, suicide attempts, suicide death, or self-harm in adults aged 50 years or older. Methodological quality was assessed using the JBI Critical Appraisal Checklist. Overlap was evaluated using the corrected covered area.ResultsEighteen systematic reviews were included, comprising 551 eligible primary-study occurrences and 423 unique publications. Depression and other mental disorders showed the strongest and most consistent associations with suicidality. Other substantial and recurrent risk indicators included loneliness, chronic pain, disability, and psychiatric comorbidities. Associations varied across suicidal ideation, suicide attempts, suicide death, and self-harm. Evidence regarding protective factors was less extensive. Purpose or meaning in life, resilience, psychological well-being, social support, connectedness, and sense of belonging were the most consistently reported protective factors.ConclusionsLate-life suicidality is associated with interacting psychiatric, physical, functional, and social factors. Clinical practice may benefit from the use of brief, multifaceted screening tools in routine care to capture these co-occurring vulnerabilities. Ultimately, suicide risk assessment in older adults must move beyond a narrow disorder-based approach toward multidisciplinary models that seamlessly integrate mental health with physical and psychosocial indicators.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261458149, identifier CRD420261458149.