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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

Abstract Background The use of tolerogenic DCs is a promising therapeutic strategy for transplantation and autoimmune disorders. Immunomodulatory DCs are primarily generated from monocytes (MDDCs) for in vitro experiments following protocols that fail to fulfil the strict regulatory rules of clinically applicable products. Here, we compared the efficacy of three different tolerance-inducing agents, dexamethasone, rapamycin and vitamin D3, on DC biology using GMP (Good Manufacturing Practice) or clinical grade reagents with the aim of defining their use for human cell therapy. Methods Tolerogenic MDDCs were generated by adding tolerogenic agents prior to the induction of maturation using TNF-α, IL-β and PGE2. We evaluated the effects of each agent on viability, efficiency of differentiation, phenotype, cytokine secretion and stability, the stimulatory capacity of tol-DCs and the T-cell profiles induced. Results Differences relevant to therapeutic applicability were observed with the cellular products that were obtained. VitD3-induced tol-DCs exhibited a slightly reduced viability and yield compared to Dexa-and Rapa-tol-DCs. Phenotypically, while Dexa-and VitD3-tol-DCs were similar to immature DCs, Rapa-tol-DCs were not distinguishable from mature DCs. In addition, only Dexa-and moderately VitD3-tol-DCs exhibited IL-10 production. Interestingly, in all cases, the cytokine secretion profiles of tol-DCs were not modified by a subsequent TLR stimulation with LPS, indicating that all products had stable phenotypes. Functionally, clearly reduced alloantigen T cell proliferation was induced by tol-DCs obtained using any of these agent. Also, total interferon-gamma (IFN-γ) secretion by T cells stimulated with allogeneic tol-DCs was reduced in all three cases, but only T cells co-cultured with Rapa-tol-DCs showed impaired intracellular IFN-γ production. In addition, Rapa-DCs promoted CD4+ CD127 low/negative CD25high and Foxp3+ T cells. Conclusions Our results demonstrate contrasting influences of different clinical-grade pharmacological agents on human tol-DC generation. This should be taken into account for decisions on the use of a specific agent for the appropriate cellular therapy in the context of a particular disease.

Introduction: Suicidal behaviors are frequently observed among patients with substance use disorder, including suicidal ideation (SI) (1). Alcohol use disorder (AUD) is one of the most prevalent addictions and may be related to suicidal behaviors (2,3). However, the association between AUD and SI requires a deeper analysis which includes several clinical features observed among AUD patients. Objectives: To analyze the clinical characteristics and features associated with lifetime SI among patients who had AUD. Methods: This is a cross-sectional study performed in an outpatient center for addiction treatment in patients seeking for treatment who met the criteria for AUD between 01/01/2010 and 12/31/2021. Patients were evaluated with an ad-hoc questionnaire and the European Addiction Severity Index (EuropASI), SI was evaluated using the item for SI in EuropASI. Results: From a potential sample of n=3729 patients, only n=1082 (73.8% males; mean age 42.82±12.51) met inclusion criteria and had data for the current analysis. Lifetime SI was present in 50.9% of the AUD patients. Several clinical features were related to SI, including: sex differences, any type of lifetime abuse, polyconsumption, benzodiazepine use disorder, any psychiatric diagnosis aside from SUD, and higher addiction severity according to the EuropASI. Image: Conclusions: SI among AUD patients is related to several clinical features which indicate a higher addiction severity, more polyconsumption, and a higher prevalence of psychiatric comorbidities. These findings may contribute to the understanding of suicidal behaviors in AUD patients but it is required further investigations, including longitudinal studies. REFERENCES 1 Rodríguez-Cintas L, et al. Factors associated with lifetime suicidal ideation and suicide attempts in outpatients with substance use disorders.  Psychiatry Res. 2018;262:440-445. doi:10.1016/j.psychres.2017.09.021 2. MacKillop J, et al. Hazardous drinking and alcohol use disorders.  Nat Rev Dis Primers. 2022;8(1):80. doi:10.1038/s41572-022-00406-1 3.Darvishi N, et al. Alcohol-related risk of suicidal ideation, suicide attempt, and completed suicide: a meta-analysis [published correction appears in PLoS One. 2020;15(10):e0241874].  PLoS One. 2015;10(5):e0126870. doi:10.1371/journal.pone.0126870 Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

OBJECTIVE: T his s tudy’s m ain objective is to carry out a systematic review of the onset of psychotic symptoms after opioid withdrawal. The opiate dependence correlated to psychiatric symptoms has been well described. MATERIALS AND METHODS: Following the PRISMA methodology. The consecutive search strategy was applied: (morphine OR buprenorphine OR oxycodone OR tramadol OR fentanyl OR remifentanil OR opioids OR heroin OR methadone) AND (Psychosis OR psychotic symptoms OR schizophrenia). RESULTS: 1 2 c ase r eports, 3 s eries o f c ases, 2 clinical studies, and 2 reviews were found. It seems that the time association is present in all of them; symptoms appear days after the interruption of the opioid. Most of the articles reported are case reports that describe symptoms that appear after the suspension of the opioid substance; in most cases, the reintroduction of the opioid had therapeutic effects and provoked a remission of these symptoms. These preliminary findings indicate that opiates could have an antipsychotic effect; however, the literature is scarce. It is critical to consider, if needed, in opioid-dependent patients who start with psychosis after the opioid withdrawal the possible replacement or reintroduction of opioids to prevent further deterioration in the patient’s mental status. CONCLUSIONS: This study encompasses a comprehensive description of the literature concerning the possible not well-studied outcome of opioid withdrawal. There are some reports of temporal association between withdrawal and psychotic symptoms that improved after the reintroduction of the opioid; it could be taken into consideration in the clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Pharmacological treatment of insomnia in patients with addictions has been hardly investigated and there are few researches about it in an inpatient detoxification. The aim of this study was to describe the outcomes of the pharmacological treatment of insomnia in SUD patients admitted to a detoxification unit in Spain, with a focus on the primary substance of abuse and co-occurring mental disorders. Methods: A quasi-experimental study was conducted in 481 addicted in patients, who were admitted for substances detoxification in Vall d´Hebron University Hospital, Barcelona, Spain, from 2010 to 2015. The patients underwent systematic evaluation of axes I and II psychiatric disorders (SCID-I, SCID-II, and CAADID). Insomnia was evaluated using a night time sleep log. Substance-dependent patients, who had insomnia during hospital detoxification, received a psychotropic medication with hypnotic effect, keeping the regular clinical practice without randomization. Results: At discharge, insomnia was considered to have been alleviated in 63.8% (n = 204) of patients while 36.2% (n = 116) of patients remained with insomnia disturbances. Comparing hypnotic treatments it was observed that mirtazapine and clotiapine were the treatment that corrected the insomnia more frequently. Discussion: Since insomnia is not corrected in all patients, it should be further investigated in medications with hypnotic purpose. Based on the results of this work, randomized clinical trials might be proposed. [ABSTRACT FROM AUTHOR]