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Ignacio Basurte-Villamor,1 Pablo Vega,2 Carlos Roncero,3– 5 José Martínez-Raga,6 Lara Grau-López,7– 10 Lourdes Aguilar,3– 5 Marta Torrens,11 Nestor Szerman12 1Department of Psychiatry and Behavioral Health, Clínica López Ibor, Madrid, Spain; 2Institute for Addictions, Madrid Salud, Madrid City Council, Madrid, Spain; 3Department of Psychiatry, University of Salamanca Healthcare Complex, Salamanca, Spain; 4Institute of Biomedicine of Salamanca, University of Salamanca, Salamanca, Spain; 5Psychiatric Unit, School of Medicine, University of Salamanca, Salamanca, Spain; 6Department of Psychiatry and Clinical Psychology, University Hospital Dr. Peset and University of Valencia, Valencia, Spain; 7Department of Psychiatry, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 8Biomedical Network Research Centre on Mental Health, CIBERSAM, Barcelona, Spain; 9Group of Psychiatry, Mental Health and Addiction, Vall d’Hebron Research Institute, Barcelona, Spain; 10Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 11Institute of Neuropsychiatry & Addictions-Hospital del Mar, Barcelona IMIM, Hospital del Mar Medical Research Institute, Barcelona University Autònoma, Barcelona, Spain; 12WADD WPA Section Dual Disorders, Mental Health and Psychiatric Institute, Gregorio Marañon University Hospital, Madrid, SpainCorrespondence: Nestor Szerman, WADD WPA Section Dual Disorders, Mental Health and Psychiatric Institute, Gregorio Marañon University Hospital, C/ Lope de Rueda 43, Madrid, 28009, Spain, Tel +34 914008690, Fax +34 915739932, Email nszermanb@gmail.comBackground: Limited studies have evaluated the effectiveness of vortioxetine in real-world settings, and none of them has involved patients with dual depression (major depressive disorder [MDD] and substance use disorder [SUD]). The objective of the study was to describe the effectiveness of vortioxetine in clinical practice and determine its effect on affective symptoms, cognitive function, quality of life, and substance use in patients with MDD and SUD.Methods: Post-authorization, retrospective, multicenter, descriptive, and observational study in 80 patients with MDD and SUD receiving a maintenance treatment with vortioxetine for six months between January 2017 and April 2021.Results: Compared with baseline, scores significantly decreased after 3 and 6 months of treatment in the Montgomery-Åsberg Depression Rating Scale total (from 28.9 to 17.7 and 12.0), and global functional impairment of the Sheehan Disability Inventory (from 26.3 to 19.1 and 16.7). The number of correct answers in the symbol digit modalities test significantly improved during vortioxetine treatment (from 40.4 to 43.8 and 48.4). Regarding the clinical global impression scale, the score for disease severity significantly decreased from 3.8 to 3.0 and 2.4. Compared with baseline, there was a significant reduction in consumption of practically all substances, especially of alcohol, cannabis, and cocaine.Conclusion: Vortioxetine was effective in clinical practice for alleviating depressive symptoms and functional impairment, and in improving cognitive and executive functions and disease severity in patients with MDD and SUD. Moreover, the treatment with vortioxetine favored a reduction in substance use and the severity of the SUDs.Keywords: vortioxetine, major depressive disorder, substance use disorder, dual disorder, major dual depressive disorder, real-world evidence

Jose Martinez-Raga,1,2 Carlos Knecht,3 Raquel de Alvaro4 1Teaching Unit of Psychiatry and Psychological Medicine, University Hospital Doctor Peset, University of Valencia, 2CEU Cardenal Herrera University, 3Área de Salud Mental, Hospital Padre Jofré, Valencia, 4Hospital General, Consorcio Hospitalario Provincial, Castellon, Spain Abstract: The α2-adrenergic receptor agonist guanfacine, in its extended-release formulation (GXR), is the most recent nonstimulant medication approved in several countries for the treatment of attention-deficit hyperactivity disorder (ADHD) as monotherapy and as adjunctive pharmacotherapy to stimulants in children and adolescents. The present paper aims to review comprehensively and critically the pharmacodynamic and pharmacokinetic characteristics and the published evidence on the efficacy and safety profile of GXR in the treatment of ADHD. A comprehensive search of relevant databases (PubMed, Embase, and PsycInfo) was conducted to identify studies published in peer-reviewed journals until January 15, 2015. Though the precise mechanism of action of guanfacine in the treatment of ADHD is not fully understood, it is thought to act directly by enhancing noradrenaline functioning via α2A-adrenoceptors in the prefrontal cortex. Weight-adjusted doses should be used, with a dosing regime on a milligram per kilogram basis, starting at doses in the range 0.05–0.08 mg/kg/day, up to 0.12 mg/kg/day. As evidenced in short-term randomized controlled trials and in long-term open-label extension studies, GXR has been shown to be effective as monotherapy in the treatment of ADHD. Furthermore, GXR has also been found to be effective as adjunctive therapy to stimulant medications in patients with suboptimal responses to stimulants. Many of the adverse reactions associated with GXR, particularly sedation-related effects, were dose-related, transient, mild to moderate in severity, and did not interfere with attention or overall efficacy. There are no reports of serious cardiovascular adverse events associated with GXR alone or in combination with psychostimulants. Keywords: guanfacine extended-release, attention-deficit hyperactivity disorder, ADHD, oppositional symptoms, adjunctive therapy, cardiovascular safety

he second part of this review deals with those neuroscientific aspects specific to the development and maintenance of dependence of three substances, two legal drugs (alcohol and tobacco) and a group of medications with abuse potential, benzodiazepines. Based on this context, the different pharmacological treatments of alcohol dependence, both related to detoxification and dehabituation, are discussed first. Treatment of the benzodiazepine withdrawal syndrome, together with the most outstanding aspects in the recent literature on relapse prevention, are reviewed. The publications on the treatment of nicotine dependence, both on replacement therapies and on bupropion, are analyzed. Finally, a critical reflection of the sources used to conduct this two-part review is done. [ABSTRACT FROM AUTHOR]

The present work focuses on the so-called dual diagnosis (DD): bipolar disorder (BD) associated with substance use disorders (SUD). Although the psychiatrists who treat patients with BD and physicians in charge of patients with SUD frequently find this association with DD, unfortunately there are few scientific works that have studied this association. The Spanish Working Group on Bipolar Disorders in Dual Diagnosis reviewed the published material using a Medline search and selected the most relevant articles. Following this, the Work Group developed an expert consensus in DD and finally, a survey was performed among a group of experts in this disorder to cover the areas that were not fully addressed by the scientific evidence or in those areas in which the Work Group was unable to reach a consensus. We conclude that, in view of the above, establishment of a consensus is a valid tool to complement the current scientific evidence. [ABSTRACT FROM AUTHOR]

Background: Recent literature suggests that ADHD is a risk factor for the development of antisocial behavior that is more severe and persistent than in community and other psychiatric populations. The combination of stimulant medication and psychotherapy (particularly cognitive behavioral therapy, CBT) is considered an evidence-based intervention for adults with ADHD. In contrast, few studies have evaluated the efficacy of medication in adult prisoners with ADHD, and the literature on the efficacy of psychotherapy is virtually nonexistent. Therefore, this article presents the protocol of a trial that will assess the efficacy of a formulation-based CBT program for inmates with ADHD., Methods: The study has a multicenter randomized controlled trial design. After screening and recruitment, participants will be randomly assigned to the CBT intervention, a general offender treatment program, or a waitlist. Pre- and post-treatment self-report and clinician-report assessments, as well as 6- and 12-month follow-up assessments will be conducted. These will include both clinical (e.g., ADHD symptoms, depression and anxiety symptoms, self-esteem, alcohol/drug abuse, treatment adherence, quality of life) and criminological (e.g., recidivism and risk of recidivism) measures. Linear mixed models will be used to assess differences between groups., Discussion: This study may be the first to evaluate the efficacy of a psychotherapy intervention in adult inmates with ADHD. It is expected that addressing the specific needs of ADHD would not only result in the previously reported clinical improvements (e.g., reduction in ADHD and comorbidity symptoms), but also reduce the risk and rate of recidivism compared to the general intervention or no intervention. However, the design may be limited by the difficulties inherent in the prison setting and in following up the sample after release., Trial Registration: ClinicalTrials.gov NCT06080373. Registered on October 12, 2023., (© 2024. The Author(s).)

Depression is a highly prevalent disorder and a leading cause of disability worldwide. It has a major impact on the affected individual and on society as a whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, the gut microbiome has emerged as a promising alternative target for treating and preventing depressive disorders. However, the microbes that form this ecosystem do not act alone but are part of a complicated network connecting the gut and the brain that influences our mood. Host cells that are in intimate contact with gut microbes, such as the epithelial cells forming the gut barrier and the immune cells in their vicinity, play a key role in the process. These cells continuously shape immune responses to maintain healthy communication between gut microbes and the host. In this article, we review how the interplay among epithelial cells, the immune system, and gut microbes mediates gut-brain communication to influence mood. We also discuss how advances in our knowledge of the mechanisms underlying the gut-brain axis could contribute to addressing depression. SIGNIFICANCE STATEMENT: This review does not aim to systematically describe intestinal microbes that might be beneficial or detrimental for depression. We have adopted a novel point of view by focusing on potential mechanisms underlying the crosstalk between gut microbes and their intestinal environment to control mood. These pathways could be targeted by well defined and individually tailored dietary interventions, microbes, or microbial metabolites to ameliorate depression and decrease its important social and economic impact., (Copyright © 2024 by The Author(s).)

Background: Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. Many patients with ASD often show behavioral problems at mealtimes, including food selectivity and atypical feeding behaviors. The Mediterranean diet (MD) has a beneficial effect on mental health for the general population across different ages. There is evidence that good adherence to the MD is effective in reducing peripheral inflammatory markers, such as the cytokine interleukin-6 (IL-6). The present study was designed to evaluate adherence to the MD in children with ASD using age- and sex-matched, typically developing individuals (TDs) as a control group and to determine whether differences in adherence to the MD are associated with salivary IL-6 and IL-6 receptor concentration., Methods: Twenty children and adolescents with ASD (mean age 9.95 ± 0.65 years) and twenty TDs (mean age: 9.85 ± 0.59 years) participated in this study (N = 16 males and N = 4 females in each group). Participants with ASD were enrolled in a psychiatric consultation in Valencia (Spain), and TDs were recruited from two public schools in Valencia. The parents of both ASD and TD groups answered the items in a validated Mediterranean Diet Quality Index for children and adolescents (KIDMED) questionnaire on their children's adherence to the MD., Results: The mean adherence to MD score was significantly lower in the ASD group (9.10 ± 0.42) (range 6-12) than in the TD group (10.35 ± 0.31) (range 8-12) ( p = 0.02, Mann-Whitney U test). There was no statistically significant association between adherence to the MD and age or sex in both groups, but there was a significant correlation between the total KIDMED score and body mass index (BMI) in the ASD group. Regarding the concentration of Il-6 and the Il-6 receptor in saliva samples, there were no significant differences between the two groups; however, linear regression analysis by group revealed significant associations between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the ASD group ( p = 0.003, OR = 0.68, 95% CI 0.007 to -0.02; p = 0.009, OR = -0.64, 95% CI -0.01 to -0.00). In contrast, no significant associations were observed between the adherence to MD score and the concentration of IL-6 and its receptor in saliva in the TD group., Conclusions: Children and adolescents with ASD showed significantly lower adherence to the MD, which can contribute to nutritional deficits described in ASD, and the role of BMI composition (fat versus lean mass) needs to be further investigated in this group. The concentration of IL-6 and its receptor in saliva is associated with adherence to the MD, suggesting a possible link between IL-6 and diet in ASD. Further studies to clarify the associations between IL-6, psychiatric alterations, and diet in ASD are needed.

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro-immuno-metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host's circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness.

Patients with gambling disorder (GD) frequently present other mental disorders, such as substance use disorder (SUDs), attention deficit/hyperactivity disorder (ADHD), mood disorders, and impulse-control disorders. We propose that GD should not be conceptualized as a single nosological entity, but rather as a gambling dual disorder (GDD). This study aims to provide further evidence of the co-occurrence of GD and other mental disorders in routine clinical practice and to identify different clinical profiles of severity. This descriptive, cross-sectional, and observational study included 116 patients with GD who were undergoing treatment in a specialized center. The MULTICAGE-CAD 4 and South Oaks gambling screen questionnaires confirmed the presence of GD in 97.4% and 100% of the patients, respectively. Other addictive behaviors such as compulsive spending, Internet, video games, or SUD (59.5%, 27.6%, 11.2%, and 13.8%, respectively) were also identified. The most used substances were tobacco (42.2%) and alcohol (5.2%). Half of the patients suffered from ADHD, 30.2% showed moderate or severe depression, and 17.2% suffered from a social anxiety problem. The majority (76.7%) also presented a phenotype with high impulsiveness. The cluster analysis identified two different clinical profiles of severity in patients with GDD. One profile showed higher severity of other mental disorders (ADHD, depression, anxiety, SUD, or insomnia), impulsivity, general psychopathological burden, and disability. In conclusion, our study provides further evidence on the co-occurrence of GD and other mental disorders supporting the GDD existence, shows impulsiveness as a vulnerability factor for GD, and identifies two clinical severity profiles., Competing Interests: Declaration of Competing Interest NS declares that he has received honoraria/expenses from Janssen, Takeda, Lundbeck, Exeltis, and Rovi. He also has participated as consulting/advisory board for Lundbeck. IBV has received research grants from Lundbeck, Otsuka, and Exeltis, and educational grants from Janssen, Lundbeck, and Exeltis. PV declares that he has received honoraria/expenses from Gilead, Abbvie, Lundbeck, and Exeltis. BM declares no conflicts of interest. JMR has been a consultant to or has received honoraria or grants from Adamed, Janssen Cilag, Lundbeck, Otsuka, Pfizer, Rovi, Servier, and Takeda. FF declares that has received honoraria and grnats from Janssen Cilag, Lundbeck, and Servier. CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The depressive disorder coexists in a high prevalence with a substance-related disorder, which is asso- ciated with a worst prognosis. The therapeutic interventions for this co-morbidity lack of the appropriate scientific sup- port. The existing evidence suggest that the currently avail- able anti-depressive drugs are of minor efficacy in this group of patients. An alternative would be the use of different drugs with distinctive neurobiological mechanism of action. The aim of this study was to describe the clinical develop- ment of a series of patients affected by this comorbidity un- der treatment with tianeptine under usual clinical practices.

Introduction: Patients with psychotic disorders often have substance use disorders and other addictions. The objective of this study was to know the current treatment situation of these patients focusing on clozapine, which was proposed in most consensus as antipsychotic of first choice in this indication., Material and Methods: A survey with 14 questions on aspects related to the treatment and management of the dual disorders was developed, emphasizing the role of clozapine in this disease., Results: The survey was answered by 199 experts in mental illnesses (90.5% physicians and 9.5% psychologists). A total of 88.4% of experts were able to prescribe clozapine, but the majority (89.4%) administered the drug to patients with resistant schizophrenia without considering a dual disorder. Only 30.8% considered the use of clozapine in patients with dual psychosis. The underutilization of clozapine in these patients was mainly attributed to controls of the pharmacovigilance plan, including frequent leukocyte count (57.1%), and lack of drug education (35.6%). The main measures proposed to increase its use are fewer blood tests (29.3%), more training (27.8%), and fewer administrative problems (25.1%)., Conclusions: In order to improve the treatment of patients with dual psychosis, it is necessary to simplify the therapy and increase the training of professionals in the use of atypical antipsychotics, especially clozapine, designed to be the drug of choice in the main expert consensus.

Background: Behavioral and psychological symptoms of dementia (BPSD) are difficult to manage and associated with poor outcome., Objectives: The aim of this study was to reach consensus on the use of antipsychotics in patients with BPSD in Spain., Methods: A qualitative, multicenter, two-round Delphi study was carried out, with the participation of specialists involved in the care of dementia patients throughout Spain. They completed a 76-item questionnaire related to the identification of BPSD, treatment with antipsychotics, follow-up of patients, barriers for the use of atypical antipsychotics, and effects of antipsychotics on quality of life., Results: A total of 162 specialists in neurology, psychiatry, and geriatrics (61% men) with a mean (SD) age of 45.9 (10) years participated in the study. Almost all participants (96.9%) strongly agreed that atypical antipsychotics are safer and better tolerated than typical antipsychotics. There was agreement on the importance to review the indication and dose of the antipsychotic drug at least every 3 months. There was consistent high rate of agreement on the beneficial impact of atypical antipsychotics on the quality of life of patients with dementia and their caregivers. A consensus was also reached on the need of detecting BPSD in patients with dementia as it decreases the quality of life of both patients and caregivers, and the need to routinely screen for dementia in elderly patients with no previous psychiatric history in the presence of suggestive symptoms of BPSD. Finally, the participants in the study agreed that administrative barriers for the prescription of atypical antipsychotics in Spain hinder the access to this drug group and favor the prescription of typical antipsychotics., Conclusions: The participants in the study agreed that atypical antipsychotics should be preferred to typical antipsychotics in the management of BPSD. Wide consensus was reached about the importance of early identification of BPSD in persons with cognitive impairment, the use and management of atypical antipsychotic drugs and their favorable impact on patients and caregiver's quality of life., (The Author(s). Published by S. Karger AG, Basel.)

Attention deficit hyperactivity disorder (ADHD) is a chronic, complex and multifactorial neurodevelopmental disorder associated with high rates of concurrent psychiatric disorders, along with problems and complications on different areas of individual functioning. ADHD is not exclusively a childhood disorder, 40-60% persisting into adulthood with an estimated prevalence of 2.5-5%. Adolescence is a stage where great and continuous changes occur, associated with a lower adherence to treatment, a greater vulnerability to the emergence of academic problems, more risk-behaviors, the onset of substance use and higher rates of other comorbid disorders. The transition to adult services or units also occurs at this stage, requiring greater coordination between child/adolescent and adult services to ensure continuity of care in a phase of life in which the patient is particularly vulnerable. As in the case of children and adolescents, the recommended treatment for adults with ADHD is the multimodal and multidisciplinary approach, that combines medication with psychological or psychosocial strategies, such as psycho-education, cognitive behavioral therapy or coaching, adapted to the individual needs of each patient. Clinical guidelines recommend psycho-stimulant drugs as first-line treatments for adult patients with ADHD.