ABSTRACT Objective Caffeine could improve cognitive functions, but study protocols usually prohibit drinking coffee before cognitive testing. However, regular coffee consumers may experience withdrawal effects when they cannot drink their habitual coffee, which may impair cognitive performance. Therefore, we tested the effects of overnight coffee abstinence in regular coffee consumers: once allowing to drink their coffee and once not drinking coffee. The cognitive performance was compared with non‐regular coffee consumers. Methods Thirty regular coffee consumers (RCCs) and 25 non‐regular consumers (N‐RCCs) took part in this study. RCCs were tested after their habitual morning coffee (c‐RCC) and after overnight abstinence (a‐RCC); N‐RCCs were tested once. A cognitive battery assessed reaction time (RT), processing speed (digit symbol substitution test), working memory, verbal learning/memory and executive function (Stroop). Sleep quality was included as a covariate. Results Compared to c‐RCC, overnight coffee abstinence significantly slowed RTs but did not affect the performance in the other cognitive tasks. In the a‐RCC condition, but not the c‐RCC condition, the RTs were slower than those of the N‐RCCs, while accuracy measures were comparable across groups. Sleep quality did not alter these findings. Conclusions Overnight coffee abstinence selectively slowed RT, and no statistical support was found for effects on memory or executive function. This suggests that overnight coffee abstinence protocols may introduce withdrawal‐related RT slowing as a confound in habitual consumers, whereas other cognitive domains may not be affected. Allowing habitual consumers to maintain normal coffee intake could reduce this bias, supporting tailored rather than uniform abstinence requirements based on the specific outcomes studied.
ABSTRACT Objective Treatment dropout undermines psychiatric trials and clinical care, and its predictors are usually studied within one diagnosis. Using harmonized individual participant data (IPD), we investigated which dropout predictors are robust across diagnoses and which are tied to study design. Method IPD analysis of seven NIMH trials ( N = 8543). A study‐stratified Cox model (race‐complete N = 6677) tested age, sex, race, and within‐study z‐scored severity, and each predictor was graded against proportional‐hazards, equal‐coefficient (follow‐up tier), leave‐one‐study‐out, random‐effects, and severity‐recoding checks. Results Lower baseline severity robustly predicted treatment completion, significant and same‐direction under every specification: z‐score, percentile‐rank and median‐split codings (HR = 1.124, p < 0.001), leave‐one‐study‐out, random‐effects pooling, and both short and long follow‐up trials. The study‐specific severity estimates were directionally consistent in all seven trials, but the magnitude of the pooled association was driven mainly by the short‐follow‐up MDD tier (HR = 1.270, p < 0.001 vs. HR = 1.057, p = 0.026), and only STAR*D reached significance on its own. Age, sex, and race were informative but study‐dependent, varying across follow‐up horizon (equal‐coefficient test rejected for age, sex, and severity) and between studies ( I 2 = 72%–84%); proportional hazards held for age and race but not severity or sex ( χ 2 = 18.1, df = 4, p = 0.001). Conclusion Baseline symptom severity is a robust, diagnosis‐spanning marker of dropout risk and a practical target for retention support, whereas age, sex, and race need study‐specific interpretation. Grading pooled estimates with assumption checks distinguishes durable transdiagnostic signals from design‐bound ones, a template for future IPD dropout research.
ABSTRACT Objective To compare serum total tau and α‐synuclein among controls, drug‐naïve children with attention‐deficit/hyperactivity disorder (ADHD) and children with ADHD receiving methylphenidate. Methods Original ELISA spreadsheets provided 26 controls, 29 evaluable drug‐naïve participants and 32 methylphenidate‐treated participants. Boundary‐coded results (> 500 pg/mL for tau; < 938 pg/mL for α‐synuclein) were assigned the recorded boundary for rank‐based analyses. Groups were compared using Kruskal–Wallis tests and Dunn–Bonferroni contrasts; within‐group associations used Spearman correlations. Results α‐Synuclein differed among groups ( H = 49.859, p < 0.001, ε 2 = 0.570), with all pairwise contrasts significant. Tau also differed ( H = 10.492, p = 0.005, ε 2 = 0.101); drug‐naïve ADHD had lower tau than controls, whereas the treated group differed from neither comparator after correction. The α‐synuclein–tau correlation remained significant after false‐discovery‐rate adjustment only in drug‐naïve ADHD ( ρ = 0.443, adjusted p = 0.048). Conclusions Serum α‐synuclein and total tau showed distinct cross‐sectional group patterns. These associations do not establish methylphenidate effects and require prospective confirmation.
OBJECTIVE:To examine whether concomitant amlodipine use was associated with steady-state serum olanzapine concentration and clinical outcomes in patients with schizophrenia. METHODS:This retrospective study included 45 inpatients with schizophrenia and hypertension who received olanzapine 10 mg/day plus amlodipine 5 mg/day (experimental group) and 52 inpatients who received olanzapine 10 mg/day alone (control group). PANSS and SDSS scores were assessed at baseline and week 7, and recorded adverse events were evaluated at week 9. RESULTS:Mean serum olanzapine concentration was lower in the combination group than in the olanzapine-alone group (40.56 ± 18.86 vs. 50.23 ± 23.41 ng/mL; unadjusted p = 0.027; age-adjusted p = 0.032) (Figure 1). Improvements in positive symptoms, negative symptoms, and SDSS scores were smaller in the combination group, whereas PANSS total and general psychopathology changes did not differ. Serum olanzapine concentration was not significantly correlated with any PANSS or SDSS change. Recorded adverse-event rates did not differ significantly. CONCLUSIONS:Concomitant amlodipine use was associated with lower serum olanzapine concentration and smaller improvements in selected clinical domains. The individual-level analyses did not establish a concentration-response relationship, and the retrospective design precludes causal inference. Haemodynamic safety could not be evaluated because complete standardised blood-pressure data were unavailable. These findings suggest that closer monitoring of clinical response and serum olanzapine concentrations may be considered when amlodipine is co-prescribed, particularly in patients with suboptimal treatment response.
OBJECTIVES:This study aimed to: (1) systematically review published cases of accidental clozapine poisoning in children and adolescents, and (2) study accidental pediatric clozapine intoxications reported to VigiBase, the global pharmacovigilance database. METHODS:A systematic review was conducted following PRISMA guidelines, and a retrospective analysis of accidental pediatric clozapine intoxication cases was performed using VigiBase. RESULTS:A systematic review identified 5 studies describing 8 cases of accidental clozapine ingestion in children aged 10 months to 10 years. The most common clinical manifestations were acute neuro-respiratory complications. One fatality was reported, in a two-year-old child. The VigiBase observational analysis included 32 accidental intoxication cases, 3 in adolescents and 29 in children under seven years of age. Among adolescents, all cases resulted from in-hospital medication administration errors; none were fatal. In the children, nearly half required prolonged hospitalization, and 2 resulted in death due to aspiration pneumonia or cardiopulmonary failure. CONCLUSIONS:Accidental clozapine poisoning in pediatric populations, although rare, can result in severe and potentially life-threatening outcomes, particularly in very young children. At home, preventive strategies are essential to reduce accidental overdose. The 3 cases of hospitalized adolescents are relatively recent, and many hospitals currently have systems in place to prevent medication errors.
