Substance use disorders and cooperative research on addictions: Spanish approach as a model.

Substance use disorders (SUD), also named addiction when it is severe, is a chronic brain disorder with serious impact on individual who suffer, the public health and with high burden of disease. They are multitude of mechanisms/factors involved in addiction: from individual characteristics of the person (from genetic to impacts of stress, sex, and age) to social and environmental situation (availability and accessibility of substances, cultural and legal aspects, socio-economical situation) and type of substance of use (pharmacological characteristics) Then, research on Addiction must include different, complementary, and translational perspectives. In this review, we explore the neurobiological, psychosocial, and epidemiological knowledge of substance addiction, and the main role played by pharmacology in the research in this field. In Spain, since 2002, collaborative networks have emerged for comprehensive research on addictions, with the creation of the Addictive Disorders Network (RTA), currently redefined as the Research Network for Primary Care in Addictions (RIAPAd) with the support of the Carlos III Health Institute (Instituto de Salud Carlos III). Basic (including neuropharmacology and behavioral pharmacology), clinical and epidemiological research groups stand out, combining efforts to address prevention, early detection and treatment through interdisciplinary cooperation and the subsequent dissemination of results.

Management of schizophrenia and comorbid substance use disorders: expert review and guidance.

BACKGROUND: Schizophrenia and substance use disorders (SUDs) are often comorbid conditions that present clinical challenges due to their heterogeneity and the difficulties associated with poor physical health, low medication adherence, high relapse and hospitalization rates, and increased risk of mortality. This is often exacerbated by a fragmented health care system that treats addiction and mental illness separately, leading to delays in proper diagnosis and treatment. MAIN TEXT: The aim of this narrative review, based on an extensive literature search and experts' clinical experience, is to synthesize evidence on the psychopathological and clinical characteristics of patients, the burden and management at the level of healthcare system, and possible gaps in the treatment of schizophrenia with comorbid SUD in order to understand and address the needs of patients. Treatment options, differences between antipsychotic medications, and the benefits of long-acting formulations and partial dopaminergic agonists are described. Partial dopamine agonists (aripiprazole, cariprazine, and brexpiprazole) have demonstrated good control of psychotic symptoms and SUDs with a favorable safety profile. CONCLUSION: Pharmacological interventions should be accompanied by psychosocial support within an integrated and multidisciplinary approach that promotes shared decision-making and a good therapeutic alliance between the entire medical team and the patient.

A systematic review of digital interventions for smoking cessation in patients with serious mental illness.

Tobacco smoking is highly prevalent among patients with serious mental illness (SMI), with known deleterious consequences. Smoking cessation is therefore a prioritary public health challenge in SMI. In recent years, several smoking cessation digital interventions have been developed for non-clinical populations. However, their impact in patients with SMI remains uncertain. We conducted a systematic review to describe and evaluate effectiveness, acceptability, adherence, usability and safety of digital interventions for smoking cessation in patients with SMI. PubMed/MEDLINE, EMBASE, CINAHL, Web of Science, PsychINFO and the Cochrane Tobacco Addiction Group Specialized Register were searched. Studies matching inclusion criteria were included and their information systematically extracted by independent investigators. Thirteen articles were included, which reported data on nine different digital interventions. Intervention theoretical approaches ranged from mobile contingency management to mindfulness. Outcome measures varied widely between studies. The highest abstinence rates were found for mSMART MIND (7-day point-prevalent abstinence: 16-40%). Let's Talk About Quitting Smoking reported greater acceptability ratings, although this was not evaluated with standardized measures. Regarding usability, Learn to Quit showed the highest System Usability Scale scores [mean (s.d.) 85.2 (15.5)]. Adverse events were rare and not systematically reported. Overall, the quality of the studies was fair to good. Digitally delivered health interventions for smoking cessation show promise for improving outcomes for patients with SMI, but lack of availability remains a concern. Larger trials with harmonized assessment measures are needed to generate more definitive evidence and specific recommendations.

New Synthetic Opioids Use among Patients in Treatment for an Opioid Use Disorder in Barcelona.

INTRODUCTION: New synthetic opioids (NSO), a class of new psychoactive substances (NPS), have recently emerged and pose an upcoming global public health challenge. The effects produced by NSO are similar to those from morphine, but they present greater pharmacological potency and abuse potential. Due to the increasing number of fatal overdoses and seizures in which NSO have been detected as heroin substitutes or adulterants, individuals with Opioid Use Disorder (OUD) represent a vulnerable population. The aim of our study was to describe and characterize from a gender perspective a Spanish cohort of potential conscious or unconscious NSO users. METHODS: A cross-sectional study was conducted in a cohort of OUD participants under treatment in addiction care services in Barcelona and Badalona, Spain. Clinical evaluation was performed through an ad hoc survey, a scale to evaluate reasons to use an opioid without prescription (range 0-4) and the Wellbeing Index (WHO-5) (range 0-100). Objective consumption of NSO was assessed by urinalysis carried out by two validated methods: high-sensitivity gas chromatography-mass spectrometry (MS) and ultra-high-performance liquid chromatography-high-resolution MS. RESULTS: A total of 154 participants with OUD were enrolled. They were mainly men (72.7%), mean age 47.8 years. Methadone was the predominant medication for opioid agonist treatment (mean dose 61.25 mg/day). A total of 32 (20.8%) participants reported having consumed some opioid to become "high" in the previous 3 months. The principal reasons for consuming illicit opioids were Replacing other drugs (mean 2.03) and Availability (mean 1.62), although Low price, was more highly valued by men (p = 0.045) and Shorter effect duration, most highly rated by women (p = <0.001). In the WHO-5, the mean score was 55 (SD = 30.1) without differences by gender. Fentanyl and derivatives or/and metabolites were detected in 7 (6.1%) participants, but illicit/non-prescribed NSOs were found in 5 out of 114 patients (4.4%), and other non-fentanyl opioids in 36 participants (26 men and 10 women). CONCLUSION: A non-negligible consumption of NSO-fentanyl's (positive detection in 6.1% of biological samples) was detected. The reasons for using these substances and also the well-being differed between the genders. There is therefore both voluntary and involuntary NSO consumption in our country which highlights the importance of approaching this potential public health problem.

Clinical practice guideline on pharmacological and psychological management of adult patients with schizophrenia spectrum disorders and a comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno del espectro esquizofrénico y un diagnóstico comórbido de trastorno por uso de sustancias.

Although correct diagnosis and management of patients with schizophrenia and a comorbid substance use disorder (SUD) would determine a decrease in morbidity and mortality in these patients, development of efficient therapeutic strategies is still pending. We present recommendations on the pharmacological and psychological management of these patients following the 'PICO' structure (Patient-Intervention-Comparison-Outcomes). Evaluation of the quality of studies and summary of the evidence for each question was performed following the recommendations of the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) working group. Our results suggest: 1) In patients with schizophrenia and cannabis use disorder, it is not possible to recommend one antipsychotic drug over another (between olanzapine, risperidone or haloperidol) for improving psychotic symptoms, reducing cannabis use, or improving pragmatic variables (weak recommendation). Clozapine cannot be recommended to reduce cannabis use (weak recommendation). 2) In patients with schizophrenia and cocaine use disorder we recommend haloperidol over olanzapine to reduce craving (moderate recommendation), and olanzapine over haloperidol to improve motor side effects in these patients (moderate recommendation). 3) In patients with schizophrenia and alcohol use disorder while naltrexone is recommended to reduce alcohol use (in terms of reducing alcohol craving) (weak recommendation), there is insufficient evidence to make any recommendation on the use of adjuvant acamprosate (weak recommendation). 4) In patients with schizophrenia and nicotine use disorder, adjuvant bupropion and varenicline are recommended for reducing nicotine use and nicotine abstinence (strong/moderate recommendation). 5) In patients with schizophrenia and polydrug use disorder, second-generation over first-generation antipsychotic drugs and olanzapine over other second-generation antipsychotics are recommended to improve psychotic symptoms (moderate/weak recommendation).

Aunque el correcto diagnóstico y manejo de los pacientes con esquizofrenia y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) determinaría una disminución de la morbilidad y mortalidad en estos pacientes, el desarrollo de estrategias terapéuticas eficientes es todavía una asignatura pendiente. Presentamos recomendaciones sobre el manejo farmacológico y psicológico de estos pacientes siguiendo la estructura PICO (Paciente-Intervención-Comparación-Outcome/resultados). Realizamos una evaluación de la calidad de los estudios y un resumen de la evidencia para cada pregunta siguiendo las recomendaciones del grupo de trabajo GRADE («Grading of Recommendations, Assessment, Development and Evaluation¼). Nuestros resultados sugieren: 1) En pacientes con esquizofrenia y trastorno por consumo de cannabis, no es posible recomendar un fármaco antipsicótico sobre otro (entre olanzapina, risperidona o haloperidol) para mejorar los síntomas psicóticos, reducir el consumo de cannabis o mejorar las variables pragmáticas (recomendación débil). No se puede recomendar la clozapina para reducir el consumo de cannabis (recomendación débil). 2) En pacientes con esquizofrenia y trastorno por consumo de cocaína, recomendamos haloperidol sobre olanzapina para reducir el craving (recomendación moderada) y olanzapina sobre haloperidol para mejorar los efectos secundarios motores en estos pacientes (recomendación moderada). 3) En pacientes con esquizofrenia y trastorno por consumo de alcohol, mientras que se recomienda naltrexona para reducir el consumo de alcohol (en términos de reducción del craving de alcohol) (recomendación débil), no hay evidencia suficiente para hacer ninguna recomendación sobre el uso de acamprosato como adyuvante (recomendación débil). 4) En pacientes con esquizofrenia y trastorno por consumo de nicotina, se recomiendan bupropión y vareniclina adyuvantes para reducir el consumo y la abstinencia de nicotina (recomendación fuerte/moderada). 5) En pacientes con esquizofrenia y trastorno por policonsumo, se recomiendan antipsicóticos de segunda generación sobre los de primera generación y olanzapina sobre otros antipsicóticos de segunda generación para mejorar los síntomas psicóticos (recomendación moderada/débil).

Clinical practice guideline on pharmacological and psychological management of adult patients with depression and a comorbid substance use disorder. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con depresión y un diagnóstico comórbido de trastorno por uso de sustancias.

Co-occurrence of depression and a substance use disorder (SUD) in patients who present dual diagnoses has been long recognized as an important consideration in clinical practice. This review synthesizes the evidence of pharmacological and psychosocial interventions for comorbid depressive disorders and SUDs while providing clinical recommendations about the best interventions to address these patients. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Our results suggest that 1) In patients with depression and alcohol consumption, the administration of non-selective serotonin reuptake inhibitor (SSRI) antidepressants instead of SSRI is recommended for improvement of depressive symptoms (strong recommendation). Neither SSRI (strong recommendation) nor non-SSRI (weak recommendation) antidepressants are recommended for reduction in alcohol consumption. 2) In patients with depression and cannabis use, the use of venlafaxine is not recommended (weak recommendation). 3) In patients with depression and cocaine consumption, the use of SSRI antidepressants for improving depressive symptoms (weak recommendation) or to reduce cocaine use is not recommended (strong recommendation). The use of non-SSRI antidepressants is only recommended for improving depressive symptoms (strong recommendation). 4) The administration of bupropion to reduce nicotine consumption is not recommended (strong recommendation). 5) Regarding psychological treatment, in patients with depression and co-occurring alcohol disorder, both pharmacotherapy and cognitive behavioural therapy have positive effects on internalizing symptoms and in reducing alcohol consumption (weak recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite evidence.

La concurrencia de depresión y un trastorno por uso de sustancias (TUS) en pacientes que presentan patología dual ha sido reconocida desde hace mucho tiempo como una consideración importante en la práctica clínica. Esta revisión sintetiza la evidencia de intervenciones farmacológicas y psicosociales para trastornos comórbidos de depresión y uso de sustancias y además proporciona recomendaciones clínicas respecto de las mejores intervenciones para tratar a estos pacientes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Nuestros resultados sugieren que: 1) en pacientes con depresión y consumo de alcohol, se recomienda la administración de antidepresivos inhibidores de la recaptación de serotonina (ISRS) no selectivos en lugar de los ISRS para mejorar los síntomas depresivos (recomendación fuerte). No se recomiendan antidepresivos ISRS (recomendación fuerte) ni antidepresivos no ISRS (recomendación débil) para reducir el consumo de alcohol; 2) en pacientes con depresión y consumo de cannabis, no se recomienda el uso de venlafaxina (recomendación débil); 3) en pacientes con depresión y consumo de cocaína, no se recomienda el uso de antidepresivos ISRS para mejorar los síntomas depresivos (recomendación débil) o para reducir el consumo de cocaína (recomendación fuerte). El uso de antidepresivos no ISRS solo se recomienda para mejorar los síntomas depresivos (recomendación fuerte); 4) no se recomienda la administración de bupropión para reducir el consumo de nicotina (recomendación fuerte), y 5) en cuanto al tratamiento psicológico, en pacientes con depresión y trastorno de alcohol concurrente, tanto la farmacoterapia como la terapia cognitivo-conductual tienen efectos positivos en la internalización de los síntomas y en la reducción del consumo de alcohol (recomendación débil). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multisitio y más grandes para proporcionar más evidencia definitiva.

Certification program of Addiction Centres for hepatitis C virus elimination in Spain. HepCelentes Project. / Programa de certificación de Centros de Adicciones para la eliminación del virus de la hepatitis C en España. Proyecto HepCelentes.

Microelimination strategies for the hepatitis C virus (HCV) in vulnerable populations, such as users of Addiction Centres (AC), are key for the elimination of hepatitis C. The aim of the HepCelentes project was to design a certification program for AC from the generation of a guide with the criteria to favour the prevention, diagnosis, control, and treatment of HCV in Spain. The project was structured in 4 phases: normalisation, implementation, certification, and communication. In the first phase, developed between July and December 2020, a Steering Committee was created (formed by representatives of scientific societies, healthcare professionals from AC, primary care centres and hospital units, and patient associations) that, from of an exhaustive bibliographic review, generated by consensus an accreditation guide for AC. The guide consists of 22 criteria (15 mandatory and 7 recommended) structured based on the requirements to be met by AC, justification for the selection, level of action (management, prevention, diagnosis and treatment/follow-up), measurement of the indicator, objective level to be achieved, evidence of compliance, clarifications to improve understanding, and mandatory / recommendation (depending on their relevance to achieve HCV elimination and its feasibility for implementation in real practice). The development of a certification system for the AC, based on consensus and coordination of multidisciplinary teams, is intended to favour the management of hepatitis C and its elimination in AC users, supporting the international, national, and regional elimination strategies.

Las estrategias de microeliminación del virus de la hepatitis C (VHC) en poblaciones vulnerables, como los usuarios de los centros de adicciones (CA), son fundamentales para lograr la eliminación de la hepatitis C. El objetivo del proyecto HepCelentes fue diseñar un programa de certificación para los CA, a partir de la generación de una guía con los criterios para favorecer la prevención, diagnóstico, control y tratamiento del VHC en España. El proyecto se estructuró en 4 fases: normalización, implementación, certificación y comunicación. En la primera fase, desarrollada entre julio y diciembre de 2020, se creó un Comité de Normalización (formado por representantes de sociedades científicas, profesionales sanitarios de CA, centros de atención primaria, unidades hospitalarias, y asociaciones de pacientes) que, a partir de una revisión bibliográfica exhaustiva, generó por consenso una guía de certificación de los CA. La guía consta de 22 criterios (15 obligatorios y 7 recomendados) estructurados en base a la definición del criterio, justificación de su selección, nivel de actuación (gestión, prevención, diagnóstico y tratamiento/seguimiento), fórmula de medición, nivel objetivo a alcanzar, evidencias de su cumplimiento, aclaraciones para mejorar su comprensión y obligatoriedad/recomendación (en función de la relevancia en la eliminación y capacidad de implementación). El desarrollo de un sistema de certificación para los CA, a partir del consenso y la coordinación de equipos multidisciplinares, pretende favorecer el manejo de la hepatitis C y su eliminación en los usuarios de los CA, apoyando las estrategias de eliminación internacionales, nacionales y autonómicas.

Clinical practice guideline on pharmacological and psychological management of adult patients with bipolar disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno bipolar y un diagnóstico comórbido de trastorno por uso de sustancias.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid bipolar disorder (BD) and substance use disorders (SUDs) while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Very few of the randomized trials performed so far have provided consistent evidence for the management of both mood symptoms and substance use in patients with a BD. No clinical trials are available for bipolar patients using cannabis. Some treatments have shown benefit for mood symptoms without benefits for alcohol or illicit substance use. Our results suggest that 1) we can (weakly) recommend the use of adjuvant valproate or naltrexone to improve symptoms of alcohol use disorder; 2) Lamotrigine add-on therapy seems to reduce cocaine-related symptoms and is therefore recommended (moderate strength); and 3) Varenicline is (weakly) recommended to improve nicotine abstinence. Integrated group therapy is the most-well validated and efficacious approach on substance use outcomes if substance use is targeted in an initial treatment phase.

Esta revisión resume las intervenciones farmacológicos y psicosociales que se han realizado en trastorno bipolar (TB) y un diagnóstico comórbido de trastorno por uso de sustancias (TUS) y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias versus los síntomas de estado de ánimo en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Muy pocos de los ensayos aleatorizados realizados hasta la fecha han proporcionado evidencia consistente para el manejo tanto de los síntomas de estado de ánimo como del uso de sustancias en pacientes con TB. No hay disponibilidad de ensayos clínicos para pacientes con TB que utilizan el cannabis. Algunos tratamientos han mostrado beneficios para los síntomas de estado de ánimo sin beneficios para el uso de alcohol o sustancias ilícitas. Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de ácido valproico o naltrexona adyuvante para aliviar los síntomas del trastorno por consumo de alcohol; 2) el tratamiento complementario con lamotrigina parece reducir los síntomas relacionados con la cocaína y, por tanto, es recomendable (fuerza moderada); y 3) la vareniclina es recomendable (débilmente) para mejorar la abstinencia de la nicotina. La terapia grupal integrada es el enfoque con más validación y eficacia sobre los resultados en el uso de sustancias cuando este uso es abordado durante la fase inicial de tratamiento.

Clinical practice guideline on pharmacological and psychological management of adult patients with an anxiety disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con un trastorno de ansiedad y un diagnóstico comórbido de trastorno por uso de sustancias.

This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for posttraumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram). Our results suggest that 1) we can (weakly) recommend the use of desipramine over paroxetine to alleviate symptoms of anxiety in patients with a PTSD and alcohol use; 2) In these patients, the use of naltrexone to reduce symptoms of anxiety is also recommended (weak strength); and 3) SSRI antidepressants vs placebo can be recommended to reduce alcohol use (weak recommendation). Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.

Esta revisión resume las intervenciones farmacológicos y psicosociales que han sido llevadas a cabo en trastornos de ansiedad con un diagnóstico comórbido de trastorno por uso de sustancias y además proporciona recomendaciones clínicas respecto de cuáles elementos de intervención son útiles para hacer frente a los síntomas del uso de sustancias y los síntomas de ansiedad en pacientes con estas afecciones concurrentes. Se utilizó la mejor evidencia de ensayos controlados aleatorizados para evaluar las opciones de tratamiento. La fuerza de las recomendaciones se describió mediante el enfoque GRADE. Hay ensayos clínicos disponibles únicamente para el trastorno por estrés postraumático (TEPT) y para el trastorno de ansiedad. En cuanto al diagnóstico comórbido de trastorno por uso de sustancias, todos los estudios han incluido pacientes con consumo de alcohol, ninguno de ellos ha abordado el consumo de cocaína, cannabis o nicotina. Aunque algunos tratamientos han mostrado beneficios para los síntomas de ansiedad sin beneficios para el consumo de alcohol u otras sustancias, solo se han ensayado enfoques farmacológicos limitados (sertralina, desipramina, paroxetina, buspirona, naltrexona y disulfiram). Nuestros resultados sugieren que 1) podemos (débilmente) recomendar el uso de desipramina sobre la paroxetina para aliviar los síntomas de ansiedad en pacientes con un TEPT y consumo de alcohol; 2) en estos pacientes, el uso de naltrexona para reducir los síntomas de ansiedad es también recomendable (fuerza débil); y 3) se pueden recomendar antidepresivos ISRS frente a placebo para reducir el consumo de alcohol (recomendación débil). Nuestra revisión pone de relieve la necesidad de realizar más investigaciones en esta área y de estudios más grandes, multisitio con muestras generalizables para proporcionar evidencia más definitiva para la práctica clínica.

Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use. / Guía de práctica clínica para el tratamiento farmacológico y psicológico de los pacientes adultos con trastorno por déficit de atención con hiperactividad y un diagnóstico comórbido de trastorno por uso de sustancias.

Substantial evidence has confirmed the high comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and a substance use disorder (SUD). This review synthesizes the pharmacological and psychosocial interventions conducted in ADHD and SUDs, and provides clinical recommendations using the GRADE approach. Our results suggest: 1) In patients with ADHD and alcohol use, atomoxetine is recommended to reduce ADHD symptoms (weak recommendation) and alcohol craving (weak recommendation). 2) In patients with ADHD and cannabis use disorder, atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to reduce cannabis use (weak recommendation). 3) In patients with ADHD and cocaine use disorder, methylphenidate is not recommended to improve ADHD symptoms or to reduce cocaine use (weak recommendation). 4) In patients with ADHD and comorbid nicotine use disorder, methylphenidate is recommended to improve ADHD symptoms (weak recommendation). Psychoestimulants, such as methylphenidate or lisdexamfetamine dimesylate, are not recommended to reduce nicotine use (weak recommendation). 5) Regarding patients with ADHD and any SUD, the use of psychostimulants is recommended to improve ADHD symptoms (weak recommendation), not to reduce substance use (weak recommendation) or to improve retention to treatment (strong recommendation). In these patients, the use of atomoxetine is recommended to improve ADHD symptoms (weak recommendation), not to decrease substance use (weak recommendation) or to improve retention to treatment (strong recommendation). Atomoxetine and psychostimulants appear to be safe in patients with any SUD (strong recommendation). Our review suggests the need for more research in this area and for larger, multisite, randomized studies to provide more definite and conclusive evidence.

La evidencia actual confirma la alta comorbilidad entre el trastorno por déficit de atención con hiperactividad (TDAH) y trastorno por uso de sustancias (TUS). Esta revisión resume las intervenciones farmacológicas y psicosociales que se han evaluado en pacientes con TDAH y TUS, y ofrece recomendaciones mediante el enfoque GRADE. Nuestros resultados sugieren: 1) En pacientes con TDAH y trastorno por uso de alcohol, la atomoxetina es recomendable para reducir los síntomas de TDAH (recomendación débil) y el craving de alcohol (recomendación débil). 2) En pacientes con TDAH y trastorno por uso de cannabis, la atomoxetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de cannabis (recomendación débil). 3) En pacientes con TDAH y trastorno por uso de cocaína, el metilfenidato no es recomendable para mejorar los síntomas de TDAH o para reducir el uso de cocaína (recomendación débil). 4) En pacientes con TDAH y trastorno por uso de nicotina, es recomendable el metilfenidato para mejorar los síntomas de TDAH (recomendación débil). Los psicoestimulantes, como metilfenidato o lisdexanfetamina, no son recomendables para reducir el uso de nicotina (recomendación débil). 5) Respecto de los pacientes con TDAH y cualquier TUS, el uso de los psicoestimulantes es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). En estos pacientes, el uso de atomexetina es recomendable para mejorar los síntomas de TDAH (recomendación débil), no para reducir el uso de sustancias (recomendación débil) o para mejorar la retención del tratamiento (recomendación fuerte). La atomoxetina y los psicoestimulantes parecen ser seguros en pacientes con cualquier TUS (recomendación fuerte). Nuestra revisión sugiere la necesidad de realizar más investigaciones en esta área y de estudios aleatorizados, multicéntricos y de mayor tamaño muestral para proporcionar más evidencia definitiva y concluyente.

Effects of cannabis exposure in the prenatal and adolescent periods: Preclinical and clinical studies in both sexes.

Cannabis is the most commonly used illicit drug among adolescents and young adults, including pregnant women. There is substantial evidence for a significant association between prenatal cannabis exposure and lower birth weight in offspring, and mixed results regarding later behavioural outcomes in the offspring. Adolescent cannabis use, especially heavy use, has been associated with altered executive function, depression, psychosis and use of other drugs later in life. Human studies have limitations due to several confounding factors and have provided scarce information about sex differences. In general, animal studies support behavioural alterations reported in humans and have revealed diverse sex differences and potential underlying mechanisms (altered mesolimbic dopaminergic and hippocampal glutamatergic systems and interference with prefrontal cortex maturation). More studies are needed that analyse sex and gender influences on cannabis-induced effects with great clinical relevance such as psychosis, cannabis use disorder and associated comorbidities, to achieve more personalized and accurate treatments.

Ultra-High Performance Liquid Chromatography-High Resolution Mass Spectrometry and High-Sensitivity Gas Chromatography-Mass Spectrometry Screening of Classic Drugs and New Psychoactive Substances and Metabolites in Urine of Consumers.

The use of the new psychoactive substances is continuously growing and the implementation of accurate and sensible analysis in biological matrices of users is relevant and fundamental for clinical and forensic purposes. Two different analytical technologies, high-sensitivity gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) were used for a screening analysis of classic drugs and new psychoactive substances and their metabolites in urine of formed heroin addicts under methadone maintenance therapy. Sample preparation involved a liquid-liquid extraction. The UHPLC-HRMS method included Accucore™ phenyl Hexyl (100 × 2.1 mm, 2.6 µm, Thermo, USA) column with a gradient mobile phase consisting of mobile phase A (ammonium formate 2 mM in water, 0.1% formic acid) and mobile phase B (ammonium formate 2 mM in methanol/acetonitrile 50:50 (v/v), 0.1% formic acid) and a full-scan data-dependent MS2 (ddMS2) mode for substances identification (mass range 100-1000 m/z). The GC-MS method employed an ultra-Inert Intuvo GC column (HP-5MS UI, 30 m, 250 µm i.d, film thickness 0.25 µm; Agilent Technologies, Santa Clara, CA, USA) and electron-impact (EI) mass spectra were recorded in total ion monitoring mode (scan range 40-550 m/z). Urine samples from 296 patients with a history of opioid use disorder were examined. Around 80 different psychoactive substances and/or metabolites were identified, being methadone and metabolites the most prevalent ones. The possibility to screen for a huge number of psychotropic substances can be useful in suspected drug related fatalities or acute intoxication/exposure occurring in emergency departments and drug addiction services.

Cocaine and depressive disorders: When standard clinical diagnosis is insufficient. / Trastorno por uso de cocaína y depresión: Cuando el diagnóstico clínico no es suficiente.

BACKGROUND: Cocaine use is a growing global health problem and patients with cocaine use disorders (CUD) present several complications, including high rates of major depression. These subjects present two types of major depressive disorder (MDD): primary major depressive disorder (P-MDD) and cocaine-induced major depressive disorder (CI-MDD). To improve treatment, it is necessary to distinguish between both types. The aim of this study was to assess the differences in depressive symptomatology criteria (P-MDD vs CI-MDD) in CUD patients. METHODS: Secondary data analysis was carried out with a cross-sectional sample of 160 patients presenting CUD and MDD. Clinical assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). A differential diagnosis was obtained between P-MDD and CI-MDD. RESULTS: Men represented 80% of the sample, the mean age was 38.61 years, and 64.5% had elementary studies. CI-MDD diagnosis (61.3%) was more frequent than P-MDD (38.7%). There was a younger age of CUD onset in CI-MDD patients. In addition, 79.4% of the patients had another substance use disorder diagnosis. The criterion "Changes in weight or appetite" was more prevalent (57.1%) in P-MDD group. CONCLUSIONS: We found differences in the criterion "Changes in weight or appetite". Further research is needed in this field to establish a differential diagnosis and thus provide better treatment for CUD patients.

Antecedentes: El consumo de cocaína es un creciente problema de salud en todo el mundo. Además, los pacientes con trastorno por consumo de cocaína (TCC) presentan una alta comorbilidad con el trastorno depresivo mayor (TDM). Estos pacientes pueden presentar dos tipos de TDM: trastorno depresivo mayor primario (TDM-P) y trastorno depresivo mayor inducido por cocaína (TDM-IC). El objetivo de este estudio es evaluar las diferencias en la sintomatología depresiva (TDM-P vs. TDM- IC) en los pacientes con TCC para mejorar su tratamiento. Métodos: Se llevó a cabo un análisis secundario en una muestra transversal de 160 pacientes que presentaban TCC y algún TDM. La evaluación clínica, así como el diagnóstico diferencial entre TDM-P y TDM-IC, se realizó utilizando la entrevista PRISM. Resultados: Los hombres representaron el 80% de la muestra con una edad media de 38,61 años y el 64,5% sólo tenía estudios primarios. El diagnóstico de TDM-IC (61,3%) fue más frecuente que el de TDM-P (38,7%). Los pacientes con TDM-IC mostraron una edad de aparición más temprana para el TCC. El 79,4% de los pacientes cumplían criterios para otro trastorno por consumo de sustancias. Únicamente el criterio "Cambios en el peso o en el apetito" fue estadísticamente más prevalente (57,1%) en los pacientes con TDM-P. Conclusiones: Existen diferencias en el criterio "Cambios en el peso o en el apetito" entre TDM-P y TDM-IC. Se necesita más investigación a fin de obtener un diagnóstico diferencial entre los dos tipos de depresión y proporcionar un mejor tratamiento para los pacientes con TCC.

Responding to global stimulant use: challenges and opportunities.

We did a global review to synthesise data on the prevalence, harms, and interventions for stimulant use, focusing specifically on the use of cocaine and amphetamines. Modelling estimated the effect of cocaine and amphetamine use on mortality, suicidality, and blood borne virus incidence. The estimated global prevalence of cocaine use was 0·4% and amphetamine use was 0·7%, with dependence affecting 16% of people who used cocaine and 11% of those who used amphetamine. Stimulant use was associated with elevated mortality, increased incidence of HIV and hepatitis C infection, poor mental health (suicidality, psychosis, depression, and violence), and increased risk of cardiovascular events. No effective pharmacotherapies are available that reduce stimulant use, and the available psychosocial interventions (except for contingency management) had a weak overall effect. Generic approaches can address mental health and blood borne virus infection risk if better tailored to mitigate the harms associated with stimulant use. Substantial and sustained investment is needed to develop more effective interventions to reduce stimulant use.

Beyond clinical outcomes: the social and healthcare system implications of hepatitis C treatment.

BACKGROUND: Hepatitis C virus (HCV) infections in people who inject drugs (PWID) can now be treated and cured. However, the impact that HCV treatment has on drug-user health, practices and wellbeing is not known. The aim of this research was to understand the non-clinical impact that HCV treatment has in PWID and their reasons for accessing and completing treatment. METHODS: Participants aged 25-67 years who had injected opioids or stimulants (currently or in the past) and had completed direct-acting antiviral treatment were recruited from seven European countries. Participants completed a 30-min online survey administered face-to-face between September 2018 and April 2019. The questionnaire responses were used to assess the mental and physical impact of having completed treatment. RESULTS: Of the 124 participants who completed the survey questionnaire, 75% were male, 69% were over 45 years old and 65% were using opioids and/or stimulants at the start of HCV treatment. Participants reported improvements in the following areas after completing HCV treatment: outlook for the future (79%); self-esteem (73%); ability to plan for the future (69%); belief in their abilities (68%); confidence (67%); empowerment (62%); energy levels (59%); and ability to look after themselves (58%). The most common reasons for starting HCV treatment were: becoming aware of treatments that were well tolerated (77%) and effective (75%); and understanding the potentially severe consequences of HCV (75%). CONCLUSIONS: The benefits of HCV treatment go beyond clinical outcomes and are linked to improved drug-user health and wellbeing. Sharing information about well-tolerated and effective HCV treatments, and raising awareness about the potentially severe consequences of untreated HCV are likely to increase the number of PWID who are motivated to access and complete HCV treatment in future.

Oral Administration of Cannabis and Δ-9-tetrahydrocannabinol (THC) Preparations: A Systematic Review.

BACKGROUND AND OBJECTIVE: Changes in cannabis legalization regimes in several countries have influenced the diversification of cannabis use. There is an ever-increasing number of cannabis forms available, which are gaining popularity for both recreational and therapeutic use. From a therapeutic perspective, oral cannabis containing Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) is a promising route of administration but there is still little information about its pharmacokinetics (PK) effects in humans. The purpose of this systematic review is to provide a general overview of the available PK data on cannabis and THC after oral administration. METHODS: A search of the published literature was conducted using the PubMed database to collect available articles describing the PK data of THC after oral administration in humans. RESULTS: The literature search yielded 363 results, 26 of which met our inclusion criteria. The PK of oral THC has been studied using capsules (including oil content), tablets, baked goods (brownies and cookies), and oil and tea (decoctions). Capsules and tablets, which mainly correspond to pharmaceutical forms, were found to be the oral formulations most commonly studied. Overall, the results reflect the high variability in the THC absorption of oral formulations, with delayed peak plasma concentrations compared to other routes of administration. CONCLUSIONS: Oral THC has a highly variable PK profile that differs between formulations, with seemingly higher variability in baked goods and oil forms. Overall, there is limited information available in this field. Therefore, further investigations are required to unravel the unpredictability of oral THC administration to increase the effectiveness and safety of oral formulations in medicinal use.

Professional perception of clozapine use in patients with dual psychosis.

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.

DSM-5 in patients seeking their first treatment for alcohol use disorder. Sex differences in the multicenter CohRTA study. / DSM-5 en pacientes que solicitan el primer tratamiento del trastorno por uso de alcohol. Diferencias de sexo en el estudio multicéntrico CohRTA.

OBJECTIVE: We aimed to analyze sex differences in the DSM-5 criteria among patients admitted to  their first treatment of alcohol use disorder (AUD). METHODS: Assessment of AUD was carried out using DSM-5 diagnostic criteria in a multicenter study (CohRTA) within the Spanish Network on Addictive Disorders. Further, baseline questionnaires including socio-demographics, family history, lifetime alcohol consumption and other substance use, as well as clinical and laboratory parameters were obtained during admission. RESULTS: 313 patients (74.8%M) were eligible; mean age at first AUD treatment was 48.8 years (standard deviation (SD): 9.9 years). Age at onset of alcohol use was 15.9 years (SD: 3.3 years) and age at starting regular alcohol consumption was 25.6 years (SD: 9.6 years). Almost 69.3% of patients were tobacco smokers and 61% had family history of AUD. Regarding other substance use, 7.7% were current cocaine users and 18.2% were cannabis users. Women started regular alcohol consumption later than men (p<,001) and used benzodiazepines more frequently (p=.013). According to DSM-5, 89.5% of cases had severe AUD (≥6 criteria). In the adjusted analysis (logistic regression), men were more likely to neglect major rules (OR=1.92, 95%CI: 1.06-3.48) and to have hazardous alcohol use (OR=3.00, 95%CI: 1.65-5.46). DISCUSSION: DSM-5 detects sex differences in patients seeking their first AUD treatment. Social impairment and risky alcohol use are significantly more frequent in men.

Objetivo: Analizar las diferencias de sexo en los criterios diagnósticos del DSM-5 de los pacientes que solicitan un tratamiento para el trastorno por uso de alcohol (TUA) por primera vez. Métodos: Pacientes incluidos entre enero 2014 y marzo 2016 en el estudio multicéntrico CohRTA de la Red de Trastornos Adictivos. El diagnóstico del TUA se realizó mediante el DSM-5. Además, se recogieron datos sociodemográficos, sobre el consumo de alcohol y otras sustancias, variables clínicas y una analítica general. Resultados: se incluyeron 313 pacientes (74,8% hombres); la edad al inicio del primer tratamiento fue de 48,8 años (desviación estándar (DE): 9,9 años), la edad al inicio del consumo de alcohol de 15,9 años (DE: 3,3 años) y la de inicio del consumo regular de 25,6 años (DE: 9,6 años). Un 69,3% de los pacientes eran fumadores y un 61% tenían antecedentes familiares de TUA. Un 7,7% eran consumidores de cocaína y un 18,2% de cannabis. Las mujeres iniciaron el consumo regular de alcohol más tarde que los hombres (p<,001) y usaban benzodiacepinas con mayor frecuencia (p=,013). Según el DSM-5, el 89,5% de los pacientes presentaban un TUA grave (≥6 criterios). En el análisis ajustado (regresión logística), los hombres tenían mayor probabilidad de presentar el criterio diagnóstico relacionado con el incumplimiento de los deberes fundamentales en el trabajo o en el hogar (OR=1,92, IC95%: 1,06-3,48) y el criterio diagnóstico de consumir alcohol en situaciones de riesgo físico (OR=3,00, IC95%: 1,65-5,46). Discusión: El DSM-5 detecta diferencias de sexo en pacientes que solicitan el primer tratamiento del TUA. El deterioro social y el consumo de alcohol de riesgo son significativamente más frecuentes en hombres.

Substance use during pregnancy and personality dimensions. / Consumo de substancias durante el embarazo y dimensiones de personalidad.

Our aim was to assess personality traits associated with substance use during pregnancy in a population-based, multicentre study of 1804 pregnant women. On day 2-3 postpartum, participants completed a semi-structured interview, including self-reported drug use (alcohol, tobacco, caffeine, cannabis, cocaine, opioids) during pregnancy, and socio-demographic, reproductive and obstetric variables, personal and family psychiatric history, social support, and the Eysenck personality questionnaire, short version (EPQ-RS). Logistic regression models were conducted. Fifty per cent of women reported substance use during pregnancy: 40% caffeine, 21% tobacco, 3.5% alcohol, and 0.3 % cannabis. Mean T-scores (SD) for personality dimensions were 51.1 (9.6) for extraversion, 48 (8.9) for psychoticism, and 43.6 (8.5) for neuroticism. Extroversion (p = .029) and psychoticism (p = .009) were identified as risk factors after adjustment by age, level of education, employment status during pregnancy, low social support, and previous psychiatric history. For each increment of 10 units in their scores, the odds of substance use increased by 12% and 16% respectively. Low education, being on leave during pregnancy, and previous psychiatric history were independent factors (p < .05) associated with substance use during pregnancy. Primiparity was a protective factor (p = .001). The final models showed a good fit (p = .26). The screening of substance use during pregnancy should include personality dimensions apart from psychosocial variables and history of psychiatric disorders. It is important to identify the associated risk factors for substance use during pregnancy to prevent and improve foetal/neonatal and maternal health during perinatal period.

Este estudio evalúa los patrones de consumo de substancias durante el embarazo y las dimensiones de personalidad asociadas, en una muestra multicéntrica de 1804 mujeres de población general. En el 2-3 día posparto, completaron una entrevista auto-administrada sobre el consumo de alcohol, tabaco, cafeína, cannabis, cocaína, opiáceos, drogas de diseño, además de variables socio-demográficas, obstétricas/reproductivas, historia psiquiátrica previa, apoyo social durante el embarazo y el cuestionario de personalidad de Eysenck (EPQ-RS). Se generaron modelos de regresión logística múltiple. La prevalencia del consumo fue del 50% (N=909): 40% cafeína, 21% tabaco, 3,5% alcohol, y 0,3 cannabis. Las puntuaciones T medias (DE) de personalidad fueron: extraversión 51,1 (9,6), psicoticismo 48 (8,9) y neuroticismo 43,6 (8,5). Las dimensiones de extraversión (p=0,029) y psicoticismo (p=0,009), fueron identificadas como factores de riesgo tras ajustar por edad, nivel educación, estatus laboral durante el embarazo, bajo apoyo social, e historia psiquiátrica previa. Para cada incremento de 10 unidades en sus puntuaciones, el odds de consumo de substancias durante el embarazo se incrementó un 12% y un 16% respectivamente. Menor educación, estar de baja, y antecedentes psiquiátricos fueron también factores independientes (p<0,05) asociados al consumo. Ser primípara fue factor protector (p=0,001). El modelo final mostró un ajuste satisfactorio (p=0,26). El cribaje de las mujeres con riesgo de consumo de substancias durante el embarazo debería incluir la personalidad además de variables psicosociales y antecedentes psiquiátricos. Identificar los factores de riesgo asociados es importante para prevenir y mejorar la salud materna y fetal/neonatal durante el embarazo y posparto.

Relationship between craving and impulsivity in patients with alcohol dependence with or without dual disorders in an outpatient treatment center: a descriptive study.

OBJECTIVES: To compare alcohol and other drugs abuse, state impulsivity, craving and the relationship between craving and impulsivity in alcohol-dependent patients with or without dual disorder attending to an alcohol treatment center in Cadiz town. METHOD: An observational, descriptive and transversal study performed on 112 alcohol dependent patient sample who were seeking treatment in ARCA outpatient treatment center in Cadiz. The sample was divided in two groups, according to present dual diagnosis or not. The sample was assessed with an AdHoc sociodemographic and clinical questionnaire and specific scales and interviews that included: 5.0 Mini International Neuropsychiatric Interview results (MINI), State Impulsivity Scale (SIS), and Multidimensional Alcohol Craving Scale (MACS). RESULTS: The prevalence of dual diagnosis was 50%, being the most prevalent disorders: Current and recurrent Major Depressive Episode Mood Disorder, Current Dysthymic Mood Disorder, Panic Disorder and Anxiety Disorder. 52,7% of the total sample had a positive result on the State Impulsivity Scale. No statistically significant results were found on the Craving Scale (neither in the score or in the sub-sections). A relationship between craving and impulsivity were found for all groups and researched items. CONCLUSIONS: As a relationship between craving and impulsivity was observed, these aspects should be considered as main factors for the treatment and evolution of alcohol- dependent patients.