Faculty Bibliography

BACKGROUND:Clinical guidelines remain unclear on which medications for gambling disorder are to be preferred in terms of efficacy and tolerability. We aimed to compare pharmacological treatments for gambling disorder in terms of efficacy and tolerability, using network meta-analysis (NMA). METHODS:Based on our pre-registered protocol [CRD42022329520], a structured search was conducted across broad range of databases, for double-blind randomized controlled trials (RCTs) of medications for gambling disorder. Data were independently extracted by two researchers. We used standardized mean differences (SMD) using Hedges' g to measure the efficacy outcomes, and for the effect for tolerability we used dropout rate due to medication side effects, expressed as odds ratio (OR). Confidence in the network estimates was assessed using the CINeMA framework. We followed the PRISMA-NMA guidelines for this work. Outcomes were gambling symptom severity and quality of life (for efficacy), and tolerability. FINDINGS/RESULTS:We included 22 RCTs in the systematic review and 16 RCTs (n = 977 participants) in the NMA. Compared with placebo, moderate confidence evidence indicated that nalmefene [Standardized Mean Difference (SMD): -0.86; 95 % confidence interval (CI: -1.32,-0.41)] reduced gambling severity, followed by naltrexone (SMD: -0.42; 95 %CI: (-0.85,0.01)). Naltrexone (SMD: -0.50; 95 %CI: (-0.85,-0.14)) and nalmefene (SMD: -0.36; 95 %CI: (-0.72,-0.01) were also more beneficial than placebo in terms of quality of life. Olanzapine and topiramate were not more efficacious than placebo. Nalmefene [Odds Ratio (OR): 7.55; 95 %CI: (2.24-25.41)] and naltrexone (OR: 7.82; 95 %CI: (1.26-48.70)) had significantly higher dropout due to side effects (lower tolerability) compared with placebo. INTERPRETATION/CONCLUSIONS:Based on NMA, nalmefene and naltrexone currently have the most supportive evidence for the pharmacological treatment of gambling disorder. Further clinical trials of novel compounds, and analysis of individual participant data are needed, to strengthen the evidence base, and help tailor treatments at the individual patient level.

INTRODUCTION/BACKGROUND:ADHD has been linked to an increased risk of completed suicide. The aim of this study was to assess the relationship between ADHD medication use and completed suicide. METHODS:This nested case-control study included individuals aged 12-49 in Quebec, Canada, diagnosed with ADHD and/or dispensed ADHD medication. Suicide cases (n = 472) between 2000 and 2021 were matched with 5 controls each (n = 2360) on date of birth, sex, and continuous public drug insurance coverage for at least 365 days before suicide death (index date). Multivariable conditional logistic regression was used to estimate the association between ADHD medication use and completed suicide. The association between specific ADHD medication types and completed suicide was also assessed. RESULTS:After controlling for potential confounders, no significant association was found between ADHD medication use and completed suicide in the overall sample, in individuals aged 12-24 and 25 to 49 years, and those with a prior ADHD physician diagnosis. No significant differences were found when comparing the use of non-stimulants only (aOR 1.27; 95 % CI: 0.62, 2.63), stimulants and non-stimulants (aOR 1.01; 95 % CI: 0.33, 3.08), and ADHD consultation without medication (aOR 0.94; 95 % CI: 0.69, 1.28) against stimulant-only use. CONCLUSION/CONCLUSIONS:Both stimulants and non-stimulants were not associated with the risk of completed suicide. These findings can inform clinical decision-making.

Systematic reviews and meta-analyses have become crucial for evidence-based decision-making in recent decades. However, it is common for the results of multiple reviews on the same topic to be inconsistent, and it is widely recognised that the results of the reviews are not always effectively communicated to healthcare professionals and the lay public. This manuscript proposes a strategy to summarise and communicate the findings of previous systematic reviews and meta-analyses to wider audiences. The proposed approach couples the findings of umbrella reviews with the creation of open-access online platforms that present the results of these umbrella reviews in an accessible way to various stakeholders. The key potential methodological avenues of this approach are presented, and specific examples from the author's own works and those from other teams are provided. An accompanying website (https://u-reach.org/) has been designed to present this Umbrella-Review, Evaluation, Analysis, and Communication Hub (U-REACH) approach and to overcome the technical challenges associated with this type of project (by sharing the code used to build existing U-REACH projects). The present document is intended to serve as a methodological and technical guide for the creation of large-scale projects designed to synthesise and disseminate scientific information to a broad audience.

OBJECTIVE:Sleep problems are highly prevalent and impairing in adolescents with ADHD. However, their relation with co-occurring mental health problems is still unclear. This study assessed whether adolescents with ADHD, with and without self-reported sleep problems, differ from each other in co-occurring mental health problems, and whether they differ from adolescents without ADHD. Furthermore, we examined whether the adolescents with ADHD and self-reported sleep problems do indeed have more disturbed sleep than the other two groups and lastly, whether these sleep differences are moderated by co-occurring mental health problems. METHOD/METHODS:Three groups of adolescents (13-17 years): 1) with ADHD and comorbid self-reported sleep problems (N = 56), 2) with ADHD but without self-reported sleep problems (N = 25), and 3) without ADHD (N = 56) were assessed. Group comparisons were done for symptoms of co-occurring mental health problems, self- and parent-reported sleep problems, and objective and subjective sleep parameters. Exploratively, moderating effects of co-occurring mental health problems on sleep differences between groups are examined. RESULTS:Compared to those without self-reported sleep problems, adolescents with ADHD and comorbid self-reported sleep problems experienced significantly more co-occurring symptoms of mental health problems, especially depression. They also scored higher on all sleep problems, and had a longer sleep onset latency and lower sleep efficiency based on subjective and objective sleep measures. Depression and anxiety moderated objectively measured sleep differences. CONCLUSION/CONCLUSIONS:Co-occurring mental health problems, especially depressive symptoms, are more prevalent in adolescents with ADHD and sleep problems and partially moderate the relation with sleep. This indicates that when adolescents with ADHD present with sleep problems in clinical practice, it is essential to also assess symptoms and other mental health problems and vice-versa.

BACKGROUND:Placebo and nocebo effects are widely reported across psychiatric conditions, yet have seldom been examined in the context of gambling disorder. Through meta-analysis, we examined placebo effects, their moderating factors, and nocebo effects, from available randomised, controlled pharmacological clinical trials in gambling disorder. METHODS:We searched, up to 19 February 2024, a broad range of databases, for double-blind randomised controlled trials (RCTs) of medications for gambling disorder. Outcomes were gambling symptom severity and quality of life (for efficacy), and drop outs due to medication side effects in the placebo arms. RESULTS:= 833) in the meta-analysis. The overall effect size for gambling severity reduction in the placebo arms was 1.18 (95%CI 0.91-1.46) and for quality of life improvement was 0.63 (0.42-0.83). Medication class, study sponsorship, trial duration, baseline severity of gambling and publication year significantly moderated effect sizes for at least some of these outcome measures. Author conflict of interest, placebo run-in, gender split, severity scale choice, age of participants or unbalanced randomisation did not moderate effect sizes. Nocebo effects leading to drop out from the trial were observed in 6% of participants in trials involving antipsychotics, while this was less for other medication types. CONCLUSION/CONCLUSIONS:Placebo effects in trials of pharmacological treatment of gambling disorder are large, and there are several moderators of this effect. Nocebo effects were measureable and may be influenced by medication class being studied. Practical implications of these new findings for the field are discussed, along with recommendations for future clinical trials.

Suicide is a significant leading cause of death among young people, particularly those struggling with mental disorders. The present study utilised data from 230 young people (aged 16-18 years) undergoing a transitional care process from Child and Adolescent Mental Health Services to Adult Mental Health Services within the MILESTONE European project (2014-2019), a longitudinal cluster randomised controlled trial. The objectives of this study were to monitor temporal patterns of general health and social functioning over two years, to detect sex differences, and to identify factors associated with Suicidal Thoughts and Behaviours (STB) at the first and last time points. The results demonstrate a decrease in STB over the two-year follow-up period among all participants. Females exhibited a higher prevalence of STB across all time points, whereas males only exhibited STB at the nine-month follow-up. The most influential factors associated with STB were previous suicide attempts and mood disorders at baseline, and mood disorders and relational problems at the end of follow-up. These findings emphasise the importance of monitoring STB and informing young people undergoing a transitional care period about its key risk factors. Moreover, sex differences in STB suggest the need for different preventive strategies for males and females.

OBJECTIVE/UNASSIGNED:Evidence on the efficacy of social skills training for adolescents with Level 1 Autism Spectrum Disorder (ASD) is unclear. METHOD/UNASSIGNED:We searched Pubmed, Scopus, and Web of Science until July 27th, 2023, for randomized controlled trials (RCTs) of social skills training for pre-adolescents and adolescents (aged 9-18) with Level 1 ASD. We then pooled data on efficacy from individual RCTs by conducting multivariate mixed-effects meta-analyses in R. We estimated possible bias in the retained RCTs using the RoB2 tool. RESULTS/UNASSIGNED:We retained 36 RCTs (encompassing 2796 participants), including 18 RCTs comparing an experimental treatment to a waiting list, and 18 RCTs comparing it to standard care/control treatment. Meta-analyses showed that experimental treatments were significantly more efficacious than waiting list or standard care/ control treatments in improving social skills (SMD = 0.3745; 95%CI = [0.2396; 0.5093]), as well as reducing behavioral symptoms (0.3154;0.1783, 0.4525) and anxious/depressive symptoms (0.2780; 0.0432, 0.5128). However, for some outcomes there was significant heterogeneity across studies and evidence of publication bias. Subgroup analyses and meta-regressions did not identify any specific clinical or demographic factors as significant predictors of outcome. The most common risk of bias across studies was related to deviations from intended interventions and measurement of the outcomes. CONCLUSIONS/UNASSIGNED:At the group level, social skills training for adolescents with Level 1 ASD is efficacious, with small-to-moderate effect size. Future research should focus on personalized medicine approaches, aimed at tailoring interventions to specific characteristics of adolescents with Level 1 ASD.

BACKGROUND:We aimed to systematically review meta-analyses on the link between attention-deficit/hyperactivity disorder (ADHD) and a broad range of psychiatric, physical, and behavioral health conditions (PROSPERO; no.CRD42023448907). RESULTS:We identified 22 meta-analyses that included 544 primary studies, covering 76 unique conditions in over 234 million participants across 36 countries and six continents. We found high-certainty evidence for the associations between ADHD and neuropsychiatric conditions (bipolar disorders, personality disorders, schizophrenia, and pragmatic language skills), night awakenings, obesity, decayed incipient surfaces, asthma, astigmatism, hyperopia and hypermetropia, strabismus, and suicide ideation. Moderate-certainty evidence suggested that ADHD was associated with headache, mood/affective disorders, depression, bruxism, bone fractures, atopic rhinitis, vision problems, suicide attempts, completed suicide, and all-cause mortality. Low-certainty evidence indicated associations with eating disorders, sleep efficiency, type 2 diabetes, dental trauma prevalence, atopic diseases, and atopic dermatitis. Very low-certainty evidence showed associations between ADHD and several sleep parameters. CONCLUSION/CONCLUSIONS:We found varied levels of evidence for the associations of ADHD with multiple health conditions. Therefore, clinicians should consider a wide range of neurological, psychiatric, sleep and suicide-related, metabolic, musculoskeletal, oral, allergic, and visual conditions, as well as the increased risk of mortality when assessing individuals with ADHD.