Luis Gutiérrez-Rojas

Background: Obsessive–compulsive symptoms frequently co-occur with depression and anxiety, contributing to a complex and potentially treatment-resistant clinical phenotype. Although transcranial magnetic stimulation (TMS) is an established treatment option for obsessive–compulsive disorder (OCD), many patients continue to experience residual symptoms across multiple domains. Multi-target neuromodulation approaches may help address overlapping neural circuits. This study evaluated the real-world effectiveness and feasibility of an accelerated Triple-Target Obsessive–Depressive–Anxious (aTTODA) theta-burst stimulation protocol. Methods: In this naturalistic cohort study, 25 patients with treatment-resistant depressive–anxious disorder and comorbid OCD were treated with TMS at a specialized neuropsychiatric center. All patients received the accelerated aTTODA protocol, consisting of 30 sessions delivered over 3 weeks. Obsessive–compulsive, depressive, and anxiety symptoms were assessed at baseline and post-treatment using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), 17-item Hamilton Depression Rating Scale (HDRS-17), and Hamilton Anxiety Rating Scale (HAM-A), respectively. Results: Treatment with the aTTODA protocol was associated with significant improvements across all symptom domains (all p < 0.001), with large within-group effect sizes (Cohen’s d ≥1.0). Mean symptom reductions were 32.7% for the Y-BOCS, 44.6% for the HDRS-17, and 42.1% for the HAM-A. For OCD symptoms, 40% of patients met response criteria and 20% achieved remission. A shift toward lower Y-BOCS severity categories was also observed following treatment, suggesting broad clinical improvement beyond changes in mean symptom scores. Conclusions: In this complex, treatment-resistant population, the accelerated multi-target aTTODA protocol was associated with clinically meaningful improvements across obsessive–compulsive, depressive, and anxiety symptom domains. These preliminary findings support the feasibility of time-efficient, circuit-based neuromodulation strategies. However, controlled randomized, blinded, sham-controlled trials are needed to establish efficacy, durability of treatment effects, and optimal patient selection.

Background: The management of schizophrenia in acute care units presents significant challenges, particularly in addressing negative symptoms and functional impairment. Cariprazine, a dopamine D3/D2 receptor partial agonist, offers a unique pharmacological profile in this setting. This review aims to provide an expert consensus on the clinical utility of cariprazine in acute settings and establish practical recommendations for its use. Methods: A comprehensive literature review was conducted across specialized databases, including PubMed/MEDLINE, EMBASE, PsycINFO, and the Cochrane Library, ensuring a robust evidence base. The consensus was developed by a panel of six senior experts during a formal consensus meeting held in Madrid. Following a structured discussion and evidence synthesis, a modified Delphi-like process was employed to refine the recommendations. The quality of evidence and the strength of the recommendations were assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. Results: The evidence confirms cariprazine’s efficacy in acute exacerbations, with a distinct advantage in treating predominant negative symptoms and hostility compared to other second-generation antipsychotics (SGAs). Its metabolic-neutral profile and D3-mediated impact on craving also make it a strategic option for patients with dual diagnosis. Conclusions: Cariprazine is a valuable tool for the stabilization and long-term functional recovery of patients in acute psychiatric units. The consensus provides a practical framework to optimize its clinical application based on high-quality evidence.

Introduction: The prevalence of tobacco smoking and high nicotine dependence (ND) in bipolar disorder (BD) is higher than in the general population but lower than in schizophrenia. This study aims to analyse the relationship of smoking behaviours, including age at onset of daily smoking (AODS), with age at onset of BD and course‐of‐illness variables –particularly recurrent suicide attempt– in a community sample of BD patients, also compared in their smoking behaviour variables with a sample of non‐psychiatric adults. Methods: Samples of 108 patients with BD and 290 non‐psychiatric adults were compared in their smoking habit. High ND was defined by a score of ≥ 6 on the Fagerström Test for Nicotine Dependence. Logistic regression analyses were employed to identify factors associated with daily smoking and high ND. Hazard curves were used to compare AODS between patients and controls and, among patients, age of BD onset between smokers and non‐smokers. Within‐subject survival times –AODS and the age at onset of BD symptoms– were compared with a multi‐state illness‐death model. Results: Compared with controls, BD patients showed higher prevalences of current daily smoking (44% vs. 34%) and high ND (25% vs. 9%); and lower smoking cessation rates (23% vs. 38%). Among BD patients, recurrent suicide attempt showed a strong independent association with both daily smoking and high ND. AODS was later in BD patients than the control group. Among patients, illness onset was earlier in smokers and AODS was earlier than illness onset. Conclusion: Addressing tobacco consumption should be an integral component of BD prevention and treatment strategies.

Introducción: El trastorno bipolar (TB) es una enfermedad mental crónica asociada a un mayor riesgo de mortalidad prematura. El consumo de tabaco es altamente prevalente en esta población y contribuye de forma relevante a la morbimortalidad física. Objetivo: Analizar críticamente la evidencia disponible sobre las intervenciones farmacológicas para el abandono del tabaco en pacientes con TB. Métodos: Se realizó una revisión narrativa estructurada en PubMed, The Cochrane Library y Web of Science, incluyendo estudios publicados entre enero de 1985 y marzo de 2025. Se incluyeron estudios originales que evaluaban tratamientos farmacológicos para la cesación tabáquica en pacientes con TB diagnosticado según criterios DSM o CIE. Debido a la heterogeneidad clínica y metodológica, no se realizó metaanálisis. Resultados: Se incluyeron 15 estudios. La mayoría evaluaron pacientes con TB dentro de cohortes psiquiátricas más amplias. La vareniclina mostró mayores tasas de abstinencia que el placebo, con odds ratios aproximadas entre 3,0 y 8,1, y fue superior al bupropión y a la terapia sustitutiva con nicotina (TSN) en varios estudios de gran tamaño. El bupropión y la TSN fueron generalmente más eficaces que el placebo, aunque con resultados menos consistentes. Los tratamientos fueron, en general, bien tolerados, sin aumento de eventos adversos neuropsiquiátricos graves. Conclusiones: Las intervenciones farmacológicas, especialmente la vareniclina, parecen efectivas y generalmente seguras para el abandono del tabaco en pacientes con TB. No obstante, la evidencia es heterogénea, lo que subraya la necesidad de estudios específicos en esta población.

Background: The trajectory and predictors of response under routine clinical care of esketamine nasal spray (ESK NS) over treatment-resistant depression (TRD) require elucidation. Methods: This retrospective, longitudinal cohort study was conducted across three Spanish centers. Adults diagnosed with TRD who initiated ESK NS and completed at least the induction phase were included. Assessments occurred at baseline, weeks 2, 4, 8, 12, 16, and at discharge. Primary outcomes included depressive severity assessed with the Montgomery–Åsberg Depression Rating Scale (MADRS), functioning assessed with the Sheehan Disability Scale (SDS), and suicidal risk assessed with the Columbia–Suicide Severity Rating Scale (C-SSRS). Multivariable logistic regression examined several response predictors. Results: The study included 50 patients (52% women). Significant improvements were observed in MADRS and SDS scores at every time point (all p < 0.001), with notable increases during weeks 8–16, coinciding with optimization phase. The median time to response was 8 weeks, and to remission was 16 weeks. The last observation across the entire cohort indicated response and remission rates of 70% and 68%, respectively. C-SSRS risk categories shifted early toward lower risk with no suicide attempts during monitored treatment. Higher Maudsley Staging Model scores, indicating greater refractoriness, independently predicted lower odds of response (OR: 0.50, 95% CI: 0.29–0.86) and remission (OR: 0.59, 95% CI: 0.36–0.97). Among those discharged, 86% remained clinically stable over approximately 10 months. Conclusions: In real-world clinical setting, ESK NS produces progressive improvements in depressive symptoms and functioning that often consolidating beyond the induction phase, especially during optimization phase.

Precision psychiatry aims to overcome clinical heterogeneity by means of biomarkers that allow predicting the clinical evolution and therapeutic response in psychiatric disorders. This literature review addresses its prognostic role and its potential integration into healthcare practice. The main objective was to compile and synthesize current evidence on prognostic biomarkers in psychiatry, evaluating their usefulness in anticipating clinical evolution, therapeutic response, and risk of relapse. A strategic search was carried out on PubMed, selecting original studies that evaluated blood, genetic, epigenetic, neuroimaging, or electrophysiological biomarkers with prognostic value. We included 30 final studies that met the established inclusion and exclusion criteria and were evaluated according to standardized scales (RoB 2, NOS, AXIS). Inflammatory biomarkers showed potential as clinical modulators. Metabolomic, neuroendocrine, and neurotrophic factors reflected specific biological profiles associated with response to treatment or risk of relapse. Functional connectivity and brain morphometry were useful in the therapeutic prediction and stratification of patients. Finally, genetics and epigenetics are consolidated as tools of sensitivity and pharmacological response. Taken together, the findings reveal specific prognostic utility based on the type of biomarker and the patient’s clinical context. Despite the current methodological limitations and scarce replication of studies, prognostic biomarkers represent a step towards a more personalized psychiatry based on biological mechanisms. The future integration of multimodal models will improve clinical decision-making.

Introduction : Attention-Deficit/Hyperactivity Disorder (ADHD) is a frequent neurodevelopmental condition in childhood. Although pharmacological treatments are effective for many patients, a substantial proportion show partial response or experience adverse effects. Nutritional strategies such as omega-3 supplementation and the Mediterranean diet have been proposed as complementary approaches to modulate symptoms and improve tolerability. Objectives : To evaluate the efficacy of omega-3 fatty acid supplementation and adherence to the Mediterranean diet on ADHD symptoms in children and adolescents. Methods: A systematic review was conducted in PubMed, Scopus, and Web of Science using the terms “Diet, Mediterranean”, “Fatty Acids, Omega-3”, and “Attention Deficit Disorder with Hyperactivity”. Studies published up to 2026 were included if they examined these interventions in participants under 18 with ADHD. Results : Twenty-three studies involving 1,838 participants met inclusion criteria. Most evaluated omega-3 supplementation, reporting mixed but generally favorable effects on attention, impulsivity, and hyperactivity. In several trials, combining omega-3 with pharmacotherapy reduced stimulant doses and adverse events. Only one randomized trial examined the Mediterranean diet, showing modest improvements limited by low adherence. Conclusion : Omega-3 supplementation may provide modest but meaningful benefits for core ADHD symptoms, particularly when combined with standard treatment. Evidence for the Mediterranean diet remains preliminary and requires further high-quality research.