ABSTRACT Objective This network meta‐analysis (NMA) aimed to evaluate the comparative efficacy of non‐invasive brain stimulation (NIBS) interventions for late‐life depression (LLD), with treatment rankings provided as a secondary outcome. Methods We conducted a systematic review and NMA of randomized controlled trials (RCTs) assessing NIBS for major depressive disorder in adults aged ≥ 60 years. Comprehensive searches of PubMed, EMBASE, and Cochrane Library were performed up to June 2025. Two reviewers independently selected studies, extracted data, and assessed quality using the Cochrane Risk of Bias tool. A random‐effects NMA was implemented using the netmeta package in R. Certainty of evidence was evaluated using the GRADE framework. Primary outcomes included changes in depressive symptoms, measured by the standard mean difference (SMD). Secondary outcomes included response rates and remission rates. Results Twenty‐five RCTs involving 1344 participants and 15 NIBS modalities were included. Bilateral electroconvulsive therapy (BL‐ECT; SMD = 1.13, 95% CI 0.37–1.90) and high‐frequency repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (rTMS‐10Hz‐F3; SMD = 0.42, 95% CI 0.02–0.81) consistently outperformed sham across all efficacy outcomes. Both interventions formed closed loops of the network geometry, enabling formal assessment of agreement between direct and indirect evidence. Although inconsistency was detected in the symptom severity network, both interventions demonstrated consistent benefits across efficacy outcomes and retained moderate‐certainty evidence. Conclusion BL‐ECT and rTMS‐10Hz‐F3 emerged as the most consistently effective NIBS treatments for LLD, supported by moderate‐certainty evidence. Other highly‐ranked modalities require cautious interpretation due to sparse data. Registration: PROSPERO (CRD42024628560).
ABSTRACT Introduction Bipolar disorder (BD) is a chronic psychiatric illness characterized by recurrent manic and depressive episodes, affecting 2% of the global population. It is associated with premature mortality, including cardiovascular disease (CVD)‐related mortality. Although clinically important, the absolute burden and incidence of cardiovascular outcomes in BD remain incompletely characterized. This systematic review and meta‐analysis synthesized observational evidence on CVD prevalence and incidence in adults with BD. Methods Following PRISMA guidelines and prospectively registered in PROSPERO (CRD42023484712), we searched PubMed, Web of Science, Embase, Scopus, and PsycInfo, screening 11,909 records. Thirty‐two observational studies in adults with BD were included after Newcastle–Ottawa Scale assessment. Data were extracted on overall CVD, coronary artery disease, cerebrovascular disease, peripheral arterial disease, comorbidities, and psychotropic exposure. Pooled prevalence and incidence rate ratios were calculated using random‐effects models when data were comparable. Results The pooled CVD prevalence in BD was 7.70% (95% CI: 5.07–11.52), with coronary artery disease at 6.89% (95% CI: 4.05–11.47), cerebrovascular disease at 4.45% (95% CI: 2.13–9.05), and peripheral arterial disease at 3.30% (95% CI: 1.66–6.45). However, prevalence estimates showed extreme heterogeneity and should be interpreted as broad indicators of absolute burden rather than precise estimates for a single BD population. In controlled incidence studies, BD was associated with increased CVD incidence (IRR 1.66, 95% CI: 1.32–2.08), with elevated coronary and cerebrovascular estimates. Clinical variable analyses involving medication use, lifestyle factors, and cardiometabolic comorbidities were not feasible because reporting was insufficient and noncomparable. Conclusion Adults with BD show substantial cardiovascular burden and increased incidence. However, extreme heterogeneity, limited incidence data, observational designs, and insufficient moderator reporting limit the precision and generalizability of pooled estimates. These findings support integrated cardiovascular screening in BD populations and future prospective studies. Trail Registration PROSPERO CRD42023484712
ABSTRACT Introduction Network meta‐analyses suggest dexamphetamines (dAMP) may yield more favourable short‐term outcomes than methylphenidate (MPH) in adults with ADHD, yet evidence on long‐term comparative persistence remains scarce. This study compared 12‐month treatment persistence between MPH and dAMP in a large multicentre cohort and explored associations with ADHD clinical presentations and objectively measured core symptoms. Methods Stimulant persistence was defined by the primary outcome, ‘time‐to‐transition’, the interval from initiation to switching stimulant classes, transitioning to non‐stimulants or complete discontinuation. Patients were censored at 12 months or at last clinical contact. A multivariable mixed‐effects Cox proportional hazard model with a random intercept for clinicians was used to estimate hazard ratios (HR) and assess the relative impact of stimulant class on persistence, including its interactions with DSM‐based clinical presentations and objective indices. Results Among 12,995 participants (49% female), 62% initiated dAMP and 38% MPH. Median time‐to‐transition was 33.1 weeks for dAMP versus 15.0 weeks for MPH. MPH was associated with a 45% increased hazard for non‐persistence compared to dAMP (HR = 1.45, 95% CI [1.36–1.55]). Regarding clinical and objective factors, hyperactive/impulsive presentation (HR = 1.14, p = 0.025) and objective impulsivity (HR = 1.05, p = 0.002) were independently associated with non‐persistence. A significant interaction was observed between stimulant class and objective hyperactivity ( p = 0.003), indicating that dAMP's persistence advantage became more pronounced with increasing motor activity (HR = 1.09). Nevertheless, these associations were secondary to the overarching effect of the stimulant class itself. Conclusion Treatment with dAMP demonstrates significantly superior 12‐month persistence compared to MPH in adults with ADHD. While clinical and objective measures of impulsivity and hyperactivity identify patients at higher risk for treatment non‐persistence, dAMP's advantage remains consistent across all presentations. These findings suggest that prioritizing dAMP may enhance long‐term treatment persistence in adult ADHD clinical practice.
ABSTRACT Background Suicide risk is elevated after prison release, but population‐level evidence on temporal risk patterns and associated factors remains limited. We aimed to describe characteristics of individuals who die by suicide after release from Norwegian prisons, compare their suicide mortality with the general population, and examine risk factors over time. Material and Methods Data from the Norwegian Prison Release Study (nPRIS), including all people in prison in Norway (2000–2022), were linked to the Norwegian Cause of Death Registry, the Norwegian Prison Registry, the Norwegian Patient Registry, and Statistics Norway. We calculated crude mortality rates (CMR) per 100,000 person‐years, standardized mortality ratios (SMR), annual age‐standardized years of life lost rate (ASYR), and Cox proportional hazards models. Results From 2000 to 2022, 1183 suicides (9.1% of all deaths; CMR 81; 95% CI 76–85) occurred after release (90% male). The SMR was higher in women (SMR 8.64; 95% CI 7.17–10.34) than men (SMR 3.98; 95% CI 3.76–4.22). In multivariable models (2009–2022; n = 57,034; 516 suicides), strong independent associations with suicide 6 months post‐release included self‐harm (adjusted HR [aHR] 4.76; 95% CI 2.60–8.72), severe mental illness (aHR 1.95; 95% CI 1.16–3.27), release from high‐security prisons (aHR 1.93; 95% CI 1.12–3.33), and pretrial detention (aHR 1.82; 95% CI 1.06–3.13). Conclusions Suicide risk is substantially and persistently elevated relative to the general population, peaks immediately after release, and is concentrated among people with prior self‐harm, severe mental illness, and those released from high‐security settings.
ABSTRACT Introduction Antipsychotic‐associated heart rate‐corrected QT (QTc) prolongation and sudden cardiac death are uncommon in young people, but risk is concentrated in patients with identifiable clinical vulnerability and during selected drug‐ or exposure‐related situations. We mapped the evidence and developed a risk‐stratified framework for clinical monitoring. Methods This structured narrative review searched PubMed in August 2026 using one comprehensive query and 41 targeted subqueries. After PMID‐based deduplication, 934 unique records underwent title screening, 382 abstract review, and 158 full‐text relevance assessment; 104 database‐derived sources met broad relevance criteria. Backward citation checking and author‐identified sources added 58 articles. Overall, 162 sources were considered and 100 providing direct, non‐redundant support were cited from the original search; three further sources were incorporated during peer review to address reviewer comments, for a final total of 103 cited references. Two authors independently assessed full‐text relevance. Youth evidence was prioritized; adult evidence was used for adult‐only agents or when youth‐specific data were unavailable. Findings were synthesized narratively without formal risk‐of‐bias or certainty assessment. Results Patient‐level factors, particularly electrolyte disturbance, bradycardia, restrictive eating disorder or medical instability, thyroid dysfunction, inherited channelopathy, structural disease, and interacting drugs, were more consistently associated with QTc risk than drug identity for many commonly used agents. Ziprasidone and pimozide had the strongest youth‐specific drug‐related signals. Adult evidence supported heightened caution with sertindole and iloperidone; high‐dose phenothiazines and amisulpride in overdose or renal impairment represented exposure‐ or context‐dependent risks. Clozapine required separate myocarditis‐focused surveillance. The evidence supports structured baseline risk assessment and targeted ECG and electrolyte testing, with repeat monitoring driven by risk factors, treatment changes, and agent‐specific warnings. Conclusion Monitoring should be tiered rather than uniformly scheduled for all patients. The proposed framework distinguishes core clinical risk assessment from targeted cardiac testing and identifies precautionary intervals that require prospective validation.
