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.

Effects of Mixing Energy Drinks With Alcohol on Driving-Related Skills.

BACKGROUND: Energy drinks (EDs) reduce sleepiness and fatigue and improve driving performance whereas alcohol does just the opposite. Although it is a trendy combination among young people, the effects of alcohol mixed with EDs on driving performance have been poorly studied. The aim was to assess if there is an interaction between the effects of both drinks on driving-related skills as well as perceptions about driving ability. METHODS: We conducted a randomized, double-blind, and placebo-controlled 4-way crossover clinical trial. Participants were 16 healthy volunteers. Interventions of 60 g of ethanol and 750 mL of Red Bull (RB) were administered in 2 separated doses. Conditions were alcohol + RB placebo, alcohol + RB, alcohol placebo + RB, and both placebos. Objective performance was assessed using a tracking test and simple reaction time, N-Back, and movement estimation tasks. Additionally, willingness to drive, other subjective effects, and ethanol and caffeine blood concentrations were also measured. RESULTS: Alcohol increased the time outside the road in the tracking test and increased simple reaction time, but the addition of RB had no main or interaction effects on performance. Nonetheless, driving-related skills after alcohol + RB were better than after alcohol alone. Willingness to drive increased with the combination of drinks. RB also reduced alcohol-induced sedation whereas drunkenness did not change. These effects were seen even though alcohol + RB increased alcohol (14.8%) and caffeine plasma concentrations (17.6%). CONCLUSIONS: Mixing EDs with alcohol predisposes consumers to drive under alcohol influence, perhaps in part because EDs counteract its detrimental effects on driving-related skills. Clinicaltrials.gov: NCT02771587.

The association between the availability of over the counter codeine and the prevalence of non-medical use.

PURPOSE: To investigate the prevalence of non-medical use (NMU) of codeine in Germany, Italy, Spain and the UK and whether availability of OTC codeine has any association with NMU of the drug. METHODS: Data collected in the online Survey of Non-Medical Use of Prescription Drugs, in surveys launched in the second half of 2018 from (Germany (n = 14,969), Italy, (n = 9974), Spain (n = 9912) and the UK (n = 9819) were analysed. For each survey, the estimated prevalence and 95% confidence interval (CI) of respondents reporting NMU of prescription and/or OTC codeine within the last 12 months were calculated and compared. RESULTS: The prevalence of last 12-month NMU in Spain was 12.6% (95% CI 11.7-13.6) for prescription codeine, 6.3% (5.6-7.0) for OTC codeine and 16.1% (15.1-17.3) for any codeine (prescription and/or OTC). The prevalence of last 12-month NMU in the UK was 5.4% (4.9-5.8) for prescription codeine, 4.5% (4.1-5.0) for OTC codeine and 8.3% (7.8-8.9) for any codeine (prescription and/or OTC). The prevalence of last 12-month NMU for prescription codeine was 2.1% (1.9-2.4) in Germany and 1.9% (1.7-2.2) in Italy. CONCLUSION: The prevalence of last 12-month NMU of any codeine product is approximately eight times greater in Spain and four times greater in the UK compared to Germany and Italy where the drug is only available by prescription. While other factors may contribute, these findings suggest that availability of codeine OTC is associated with greater NMU.

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.

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.

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.

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.

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.

Non-Linear Formation of EtG and FAEEs after Controlled Administration of Low to Moderate Doses of Ethanol.

AIMS: Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of alcohol that can be detected in conventional and non-conventional biological matrices for longer periods than alcohol. The aim was to describe the time courses of both biomarkers after ingestion of acute low-moderate doses of ethanol. METHODS: The study design was double-blind, randomized, crossover and controlled with placebo. Participants were distributed in three different cohorts: (a) Cohort-1: two doses of 18 and 30 g of ethanol and placebo were administered to 12 subjects; (b) Cohort-2: two doses of 6 and 12 g of ethanol and placebo were administered to six subjects and (c) Cohort-3: two doses of 24 and 42 g of ethanol and placebo were administered to six subjects. Each participant received two doses of ethanol and placebo. Plasma concentrations (0-6 h) of ethanol and specific FAEEs (palmitic, stearic, linoleic and oleic acid ethyl esters) and urinary concentrations of EtG (0-24 h) were measured. RESULTS: A dose-dependent increase in blood ethanol concentrations was observed. EtG excretion and FAEEs plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. Area under the curve (AUC0-6h) of ethanol concentrations showed a linear trend with non-oxidative metabolites' concentrations. CONCLUSION: The formation rate of ethanol non-oxidative biomarkers does not follow a linear trend, explained mainly by a disproportionate increase in AUC0-6h of ethanol concentrations in relation to dose. This observation should be taken into account when interpreting results in biological matrices in clinical and forensic settings. SHORT SUMMARY: A double-blind, randomized, crossover and controlled study was conducted administering ethanol (6-42 g). Ethyl glucuronide (EtG) excretion and fatty acid ethyl esters (FAEEs) plasmatic concentrations showed a disproportionate increase with the ethanol dose suggesting non-linearity. This observation should be taken into account when interpreting biomarker concentrations in clinical settings.

Patient Management and Psychopharmacological Treatment Associated to Smoking Ban in an Acute Psychiatric Unit.

This study investigates differences in terms of clinical and treatment management in psychiatric hospitalization associated to smoking ban. We collected data regarding medication, socio-demographic and admission characteristics from all patients admitted to an acute psychiatric hospital before and after a smoking ban was in force. We also assessed a limited sample of patients before and after the ban regarding nicotine dependence, motivation to quit smoking and attitudes towards the ban. More number of leaves of absence and movement restrictions during the ban period occurred in comparison to the pre-ban period. On the contrary a lack of significant differences in terms of hospital stay (duration, rate of voluntary admissions and voluntary discharges), use of sedatives and doses of antipsychotics was found. A period of adjustment regarding the deal with leave of access and facilitate nicotine replacement treatment may help future psychiatric facilities planning smoking free policies.

Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects.

Cocaine addiction is characterized by persistent decision-making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine-dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting-state activation. Ten cocaine-dependent subjects and 14 non-drug-using controls participated in the study. Cocaine-dependent subjects were carefully selected to discard potentially confounding co-morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting-state. During the moral dilemmas task, cocaine-dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting-state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine-dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making.

Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy.

BACKGROUND: Concern regarding the QTc interval in human immunodeficiency virus (HIV)-infected patients has been growing in recent years, and cases of prolonged QTc interval and torsades de pointes have been described in HIV-infected patients on methadone therapy. This study aimed to determine the prevalence and factors associated with long QTc interval in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. METHODS: A cross-sectional study was conducted in opioid-dependent HIV-infected patients on methadone maintenance therapy at a drug abuse outpatient center. Patients with any cardiac disease, drug-positive urine test, electrolyte abnormalities, and changes in their antiretroviral therapy (ART) or methadone doses in the last 2 months were excluded. Heart rate and QT interval in lead II were measured using the Bazett formula. RESULTS: Ninety-one patients were included: 58 (63.7%) were men with a median age of 44.5 years and 68 of 91 (74.7%) were on ART. Median methadone dose was 70 mg/day (range 15-250 mg/day) and mean QTc interval was 438 ± 34 ms. Prolonged QTc interval (>450 ms) was documented in 33 of 91(36.3%) patients, and 3 of 91 (3.2%) had QTc >500 ms. On multiple linear regression analysis, methadone doses (P = .005), chronic hepatitis C-induced cirrhosis (P = .008), and being ART-naive (P = .036) were predictive of prolonged QTc. CONCLUSIONS: The prevalence of prolonged QTc interval in opioid-dependent HIV-infected patients on methadone maintenance therapy is high. Risk factors for prolongation of the QTc interval are chronic hepatitis C-induced cirrhosis, higher methadone doses, and being ART-naive. Thus, electrocardiographic monitoring is required to minimize cardiovascular morbidity and mortality in this specific HIV group.

Methadone maintenance treatment in Spain: the success of a harm reduction approach.

PROBLEM: During the 1980s, Spain had very strict laws limiting access to opioid agonist maintenance treatment (OAMT). Because of this, mortality among people who used illicit opioids and other illicit drugs was high. Spain was also the European country with the highest number of cases of acquired immunodeficiency syndrome transmitted through illicit drug injection. APPROACH: The rapid spread of human immunodeficiency virus (HIV) infection among people using heroin led to a shift from a drug-free approach to the treatment of opioid dependence to one focused on harm reduction. A substantial change in legislation made it possible to meet public health needs and offer OAMT as part of harm reduction programmes in the public health system, including prisons. LOCAL SETTING: Legislative changes were made throughout the country, although at a different pace in different regions. RELEVANT CHANGES: Legal changes facilitated the expansion of OAMT, which has achieved a coverage of 60%. A parallel reduction in the annual incidence of HIV infection has been reported. Reductions in morbidity and mortality and improved health-related quality of life have been described in patients undergoing OAMT. LESSONS LEARNT: The treatment of opioid dependence has been more heavily influenced by moral concepts and prejudices that hinder legislation and interfere with the implementation of OAMT than by scientific evidence. To fulfil public health needs, OAMT should be integrated in harm reduction programmes offered primarily in public facilities, including prisons. Longitudinal studies are needed to detect unmet needs and evaluate programme impact and suitability.

Substance use Specificities in Women with Psychosis: A Critical Review.

BACKGROUND: Women with schizophrenia or other psychotic disorders differ from male patients in many respects, including psychopathology, prognosis, disease course, and substance use comorbidities. Most studies performed to date to investigate the association between drug use and psychosis have not evaluated gender differences, although this has started to change in recent years. METHODS: We briefly summarize the available evidence on gender differences in drug use and substance use disorders (SUD) in psychotic patients during the early phases of the psychotic illness and during the course of schizophrenia. RESULTS: Substance use and SUD are both less prevalent in women, both in the general population and at all phases of the psychotic spectrum. Some studies suggest that SUD may be under diagnosed in female patients, in part due to their more vulnerable profile. Substance use, especially cannabis, may more negatively impact females, especially on the disease course and prognosis. The available data suggest that it may be more difficult to treat SUD in female patients with schizophrenia, which could negatively impact prognosis. CONCLUSION: Women with concomitant psychotic illness and SUD comprise a highly vulnerable subgroup. This should be considered when selecting the treatment approach, especially in the early phases of the illness, to ensure better outcomes.

Pharmacological effects of methylone and MDMA in humans.

Methylone is one of the most common synthetic cathinones popularized as a substitute for 3,4-methylenedioxymethamphetamine (MDMA, midomafetamine) owing to its similar effects among users. Both psychostimulants exhibit similar chemistry (i.e., methylone is a ß-keto analog of MDMA) and mechanisms of action. Currently, the pharmacology of methylone remains scarcely explored in humans. Herein, we aimed to evaluate the acute pharmacological effects of methylone and its abuse potential in humans when compared with that of MDMA following oral administration under controlled conditions. Seventeen participants of both sexes (14 males, 3 females) with a previous history of psychostimulant use completed a randomized, double-blind, placebo-controlled, crossover clinical trial. Participants received a single oral dose of 200 mg of methylone, 100 mg of MDMA, and a placebo. The variables included physiological effects (blood pressure, heart rate, oral temperature, pupil diameter), subjective effects using visual analog scales (VAS), the short form of the Addiction Research Center Inventory (ARCI), the Evaluation of Subjective Effects of Substances with Abuse Potential questionnaire (VESSPA-SSE), and the Sensitivity to Drug Reinforcement Questionnaire (SDRQ), and psychomotor performance (Maddox wing, psychomotor vigilance task). We observed that methylone could significantly increase blood pressure and heart rate and induce pleasurable effects, such as stimulation, euphoria, wellbeing, enhanced empathy, and altered perception. Methylone exhibited an effect profile similar to MDMA, with a faster overall onset and earlier disappearance of subjective effects. These results suggest that abuse potential of methylone is comparable to that of MDMA in humans. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05488171; Identifier: NCT05488171.

Meta-analysis of the effects of adjuvant drugs in co-occurring bipolar and substance use disorder.

BACKGROUND: Individuals with bipolar disorder (BD) often have co-occurring substance use disorders (SUDs), which substantially impoverish the course of illness. Despite the importance of this dual diagnosis, the evidence of the efficacy and safety of adjuvant treatments is mostly unknown. OBJECTIVE: To perform a meta-analysis to evaluate the efficacy and safety of adjuvant drugs in patients with co-occurring BD and SUD. METHODS: We searched PubMed, Scopus, and Web of Knowledge until 30th April 2022 for randomized clinical trials (RCT) evaluating the efficacy and safety of adjuvant drugs compared to placebo in patients with a dual diagnosis of BD and SUD. We meta-analyzed the effect of adjuvant drugs on general outcomes (illness severity, mania, depression, anxiety, abstinence, substance craving, substance use, gamma-GT, adherence, and adverse events) and used the results to objectively assess the quality of the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. For completeness, we also report the specific effects of specific adjuvant drugs in patients with specific substance disorders. RESULTS: We included 15 RCT studies (9 alcohol, 3 cocaine, 2 nicotine, and 1 cannabis) comprising 628 patients allocated to treatment and 622 to placebo. There was low-quality evidence that adjuvant drugs may reduce illness severity (g=-0.25, 95% CI: -0.44, -0.06), and very-low quality evidence that they may decrease substance use (g=-0.23, 95% CI: -0.44, -0.02) and increase substance abstinence (g=0.21, 95% CI: 0.04, 0.38). DISCUSSION: There is low-quality evidence that adjuvant drugs may help reduce illness severity, probably via facilitating abstinence and lower substance use. However, the evidence is weak; thus, these results should be considered cautiously until better evidence exists.

BDNF and Cortisol in the Diagnosis of Cocaine-Induced Depression.

Background: Major depressive disorder (MDD) and cocaine use disorder (CUD) are related with disability and high mortality rates. The assessment and treatment of psychiatric comorbidity is challenging due to its high prevalence and its clinical severity, mostly due to suicide rates and the presence of medical comorbidities. The aim of this study is to investigate differences in brain derived neurotrophic factor (BDNF) and cortisol plasmatic levels in patients diagnosed with CUD-primary-MDD and CUD-induced-MDD and also to compare them to a sample of MDD patients (without cocaine use), a sample of CUD (without MDD), and a group of healthy controls (HC) after a stress challenge. Methods: A total of 46 subjects were included: MDD (n = 6), CUD (n = 15), CUD-primary-MDD (n = 16), CUD-induced-MDD (n = 9), and 21 HC. Psychiatric comorbidity was assessed with the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders IV (PRISM-IV), and depression severity was measured with the Hamilton Depression Rating Scale (HDRS). Patients were administered the Trier Social Stress Test (TSST) before and after the biological measures, including BDNF, and cortisol levels were obtained. Results: After the TSST, Cohen's d values between CUD-primary-MDD and CUD-induced-MDD increased in each assessment from 0.19 post-TSST to 2.04 post-90-TSST. Pairwise differences among CUD-induced-MDD and both MDD and HC groups had also a large effect size value in post-30-TSST and post-90-TSST. In the case of the BDNF concentrations, CUD-primary-MDD and CUD-induced-MDD in post-90-TSST (12,627.27 ± 5488.09 vs.17,144.84 ± 6581.06, respectively) had a large effect size (0.77). Conclusion: Results suggest a different pathogenesis for CUD-induced-MDD with higher levels of cortisol and BDNF compared with CUD-primary-MDD. Such variations should imply different approaches in treatment.