To outline the life and work of Greek physician Asclepiades of Bithynia (124–40 BC), especially his contributions to thinking about mental illness.

Review and discussion of relevant fragments of Asclepiades’ work that survive and review of secondary literature, supplemented by relevant systematic literature searches (e.g. PubMed).

Asclepiades challenged the long-standing Hippocratic doctrine of the four humours and developed an approach to physical and mental illness that was humane, reasoned, and a forerunner of later developments in psychiatry. Asclepiades argued that the human body, like everything in the universe, comprised tiny, imperceptible particles, which he called önkoi, seamless masses in perpetual motion. In consequence, Yapijakis describes Asclepiades as ‘the father of molecular medicine’. Asclepiades held that good health was maintained by free, balanced motion of önkoi through theoretical pores, while disease resulted from blockage or impaction of önkoi passing through pores in various body parts (e.g. brain). Based on this idea, Asclepiades recommended releasing people with apparent mental illness from confinement and using judicious combinations of diet, exercise, massage, bathing, and music to treat ‘phrenitis’ (delirium) and melancholia. He suggested that the physician act ‘safely, swiftly and pleasantly’ (‘cito, tutu, jucunde’) for both physical and mental illness.

Asclepiades belongs to the historical tradition of progressive medical approaches to mental illness, not least because he applied his principles for the treatment of physical illness to mental illness. His ideas about psychiatry set the scene for further evolution of attitudes to mental illness and its treatment over subsequent centuries.

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.

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.

We included 16 RCTs (n = 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.

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.

Giant coronary artery aneurysms are rare but potentially fatal complications of Kawasaki disease. The lack of evidence-based recommendations on their management and treatment cause guidelines and practices to differ. We aimed to assess these variations.

An anonymous online survey regarding surveillance, imaging, pharmacological management, and interventional practices was distributed among 134 physicians attending to Kawasaki disease patients worldwide. A p-value of <0.05 was deemed significant.

The majority (60%) of respondents were general paediatric cardiologists, and 29% interventional specialists. The average years in practice was 15 ± 9.6. Physicians from Asia had the most experience with giant coronary artery aneurysms. American practitioners preferred combining anticoagulants with aspirin. Beta-blockers and statins were more likely used in teenagers versus younger children. Cardiac catheterisation was most (52%) chosen for coronary surveillance in patients with echocardiogram anomalies, followed by Coronary CT-angiography. The indications for coronary intervention were split among respondents, regardless of geographic region or experience. The preferred treatment of coronary stenosis was percutaneous intervention (69%) versus bypass surgery. For thrombosis, thrombolytics (50%) were preferred over percutaneous (39%) and surgical (11%) interventions. Most (92%) preferred intervening in young children in a paediatric facility but were split between a paediatric and adult facility for older children. Most chose combined management by adult and paediatric specialists for either age-scenarios (70, 82%).

As identified by our study, the lack of large studies and evidence-based recommendations cause uncertainty and ambivalence towards certain treatments. International collaborative efforts are needed to provide more robust evidence in the management of these patients.

The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Cognitive impairment (CI) is one of the most prevalent and burdensome consequences of COVID-19 infection, which can persist up to months or even years after remission of the infection. Current guidelines on post-COVID CI are based on available knowledge on treatments used for improving CI in other conditions. The current review aims to provide an updated overview of the existing evidence on the efficacy of treatments for post-COVID CI.

A systematic literature search was conducted for studies published up to December 2023 using three databases (PubMed–Scopus–ProQuest). Controlled and noncontrolled trials, cohort studies, case series, and reports testing interventions on subjects with CI following COVID-19 infection were included.

After screening 7790 articles, 29 studies were included. Multidisciplinary approaches, particularly those combining cognitive remediation interventions, physical exercise, and dietary and sleep support, may improve CI and address the different needs of individuals with post-COVID-19 condition. Cognitive remediation interventions can provide a safe, cost-effective option and may be tailored to deficits in specific cognitive domains. Noninvasive brain stimulation techniques and hyperbaric oxygen therapy showed mixed and preliminary results. Evidence for other interventions, including pharmacological ones, remains sparse. Challenges in interpreting existing evidence include heterogeneity in study designs, assessment tools, and recruitment criteria; lack of long-term follow-up; and under-characterization of samples in relation to confounding factors.

Further research, grounded on shared definitions of the post-COVID condition and on the accurate assessment of COVID-related CI, in well-defined study samples and with longer follow-ups, is crucial to address this significant unmet need.

Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults.

Participants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU (n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling.

Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85–9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month (B = −4.00, p = 0.009, 95% CI −6.97 to −1.02, d = 0.27) and 6-month follow-up (B = −3.20, p = 0.032, 95% CI −6.13 to −0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month (B = −0.57, p = 0.732, 95% CI −3.83 to 2.69) nor after 6-month follow-up (B = −0.44, p = 0.793, 95% CI −3.69 to 2.82).

The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use.

Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).