Antiseizure medications (ASMs) are the mainstay of epilepsy treatment but may adversely affect cognitive functions, deepening the cognitive and psychosocial burden intrinsic to epilepsy. Cognitive side effects vary widely across drug classes, doses, treatment regimens, and individual susceptibility, typically affecting attention, processing speed, memory, language, and executive function. This narrative review provides an updated synthesis of the clinical evidence on the cognitive effects of ASMs, mostly in adults, building on a prior 2009 review and focusing on agents introduced into clinical practice since then. A literature search of PubMed identified studies published between January 2009 and December 2025, yielding data from randomised controlled trials, observational studies, meta-analyses, and systematic reviews. Overall, newer-generation ASMs, including rufinamide, lacosamide, brivaracetam, cannabidiol, fenfluramine, and ganaxolone, demonstrate generally favourable cognitive profiles when used at recommended doses, particularly in monotherapy or rational polytherapy. Eslicarbazepine and cenobamate may be associated with mild, dose-dependent cognitive effects, occurring only at the upper end of the recommended dose range. In contrast, old ASMs and certain second-generation agents, notably topiramate and zonisamide, remain consistently associated with higher cognitive risks. Special populations, including older adults and individuals with intellectual disabilities, are particularly vulnerable to cognitive adverse effects and benefit from agents with low interaction potential and benign neuropsychological profiles. Cognitive dysfunction in epilepsy is multifactorial, reflecting the interaction between disease-related neurobiological mechanisms and treatment effects. Optimal management requires balancing seizure control with cognitive preservation through individualised drug selection, cautious titration, and minimisation of polytherapy to achieve the best functional and quality-of-life outcomes.
Psychedelic microdosing has gained increasing popularity for enhancing mood and cognition, yet its effects on psychological outcomes in healthy adults remain unclear. We aim to evaluate the efficacy and safety of psychedelic microdosing on psychological outcomes in healthy/non-clinical adult population. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251035294). We searched Embase, MEDLINE, and PsycINFO from inception to February 2026 for original studies in healthy adults using sub-hallucinogenic psychedelic doses on separate days. We included randomized studies, nonrandomized prospective studies, cross-sectional studies, and observational longitudinal designs and stratified meta-analyses by design. Random-effects models were used; safety in randomized controlled trials (RCTs) was pooled as risk differences (RDs). Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. 24 studies (3,681 participants) met inclusion criteria, 6 contributed to meta-analyses. RCTs of psilocybin and LSD microdosing showed subjective and neurophysiological effects but minimal impact on cognition, creativity, or sustained mood. Psilocybin altered EEG and speech with little behavioral change, while LSD caused transient mood and minor physiological effects without lasting cognitive or personality benefits. Observational studies indicated mood and personality improvements, likely influenced by expectancy or lifestyle factors. Meta-analyses included two parallel RCTs (3 comparisons; n = 117) and three non-RCT studies (n = 1,013). Adverse event analyses included two RCTs (4 comparisons; n = 109). RCTs showed no clear evidence of immediate symptom reduction: depressive symptoms (SMD = −0.19; 95
Teriflunomide is widely used as an active comparator in Phase 3 randomised trials for relapsing multiple sclerosis (RMS). Temporal changes in disease activity within teriflunomide-treated cohorts have not been systematically examined. To assess temporal trends in relapse and disability outcomes across teriflunomide arms of Phase 3 multiple sclerosis (MS) trials and identify predictors of between-trial heterogeneity. We performed a systematic review and meta-analysis of Phase 3 randomised controlled trials including a teriflunomide arm. PubMed, Scopus, and ClinicalTrials.gov were searched up to October 2025. Annualised relapse rate (ARR) and 12- and 24-week confirmed disability worsening (CDW) were extracted together with baseline characteristics. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses, meta-regression, and sensitivity analyses were performed. Twelve teriflunomide cohorts from eight trials involving 4,900 adults with RMS were included. ARR ranged from 0.11 to 0.37 with substantial heterogeneity (I2 = 94
Randomised controlled trials (RCTs) have demonstrated that pharmacotherapy reduces symptoms of attention-deficit/hyperactivity disorder (ADHD) at a group level, but efficacy and tolerability vary across individuals. Clinico-demographic characteristics may act as predictors and/or moderators of treatment efficacy and tolerability, but systematic evidence remains limited. Therefore, we systematically analysed RCTs of ADHD medications to identify potential demographic and clinical predictors/moderators of efficacy and tolerability across the lifespan. Randomised controlled trials were identified from the MED-ADHD database ( https://med-adhd.org/ ), a repository of RCTs of medications for ADHD in children, adolescents and adults. The database is based on systematic searches of multiple electronic sources, including PubMed, BIOSIS Previews, CINAHL, the Cochrane Central Registry of Controlled Trials and EMBASE, and is also complemented by unpublished data obtained from manufacturers and study authors. We used the most recent (2026) version of MED-ADHD. The risk of bias was assessed using the revised Cochrane risk-of-bias tool (RoB 2). Among the 171 RCTs screened, 62 assessed clinico-demographic factors as possible predictors or moderators of treatment efficacy and tolerability. Age was the most examined characteristic (56.4
