Lamotrigine Augmentation of Serotonin Reuptake Inhibitors in Severe and Long-Term Treatment-Resistant Obsessive-Compulsive Disorder

The treatment recommendations in obsessive-compulsive disorder (OCD) after lack of response to selective serotonin reuptake inhibitors (SSRIs) include augmentation with other drugs, particularly clomipramine, a more potent serotonin reuptake inhibitor (SRI), or antipsychotics. We present two cases of response to lamotrigine augmentation in treatment-refractory OCD; each received multiple SRI trials over a \u3e10-year period. The first patient had eleven years of treatment with multiple combinations including clomipramine and SSRIs. She had a \u3e50% decrease of Y-BOCS (from 29 to 14) by augmenting paroxetine (60 mg/day) with lamotrigine (100 mg/day). The second patient had 22 years of treatment with multiple combinations, including combinations of SSRIs with clomipramine and risperidone. She had an almost 50% decrease of Y-BOCS (from 30 to 16) and disappearance of tics by augmenting clomipramine (225 mg/d) with lamotrigine (200 mg/day). These two patients were characterized by lack of response to multiple treatments, making a placebo response to lamotrigine augmentation unlikely. Prospective randomized trials in treatment-resistant OCD patients who do not respond to combinations of SSRIs with clomipramine and/or antipsychotics are needed, including augmentation with lamotrigine. Until these trials are available, our cases suggest that clinicians may consider lamotrigine augmentation in such treatment-resistant OCD patients

First-time admissions for opioid treatment: crosssectional and descriptive study of new opioid users seeking treatment

Background: The purpose of this study was to gain an understanding of the profiles of the new treatment demands posed by opioid addicts between 2005 and 2010 at the addictive disorders assistance units in Galicia, Spain. Methods: A cluster analysis was performed using data from 1,655 treatment entrants. Clusters were constructed using sociodemographic and medicolegal variables. A cluster analysis was also conducted according to age. Once clusters were defined, their association with the following variables was analyzed: age at first use of opioids, years of use, frequency of opioid use in the previous month, psychiatric treatment, cocaine use, existence of a drug-dependent partner, and source of referral. Results: Four clusters were obtained in the main analysis. Cluster 1 (34.01%) consisted of young males, cluster 2 (16.19%) consisted of not-so-young males, cluster 3 (32.62%) consisted mainly of older males and a small group of females, and cluster 4 (17.18%) was made up entirely of women. With regard to age-related clusters, two clusters were obtained in those under the age of 30 years: cluster 1 (73%) without medicolegal complications and cluster 2 (27%) with medicolegal complications. For those over the age of 30 years, two clusters were obtained: cluster 1 (53.92%) with hardly any medicolegal complications and cluster 2 (46.08%) with medicolegal complications. Conclusion: Cluster analysis suggests that there have been no substantial changes in variables indicating greater severity in this new group of patients. Women are likely to seek help earlier, which reduces their duration of opioid use. The younger the patient, the shorter the duration of opioid use and the greater the likelihood of cessation of intravenous use. Public health systems should use a two-pronged treatment strategy of short but intense cessation therapies for women and younger treatment entrants and longer maintenance and replacement therapies for older treatment entrants with more psychosocial and medical complications.This study was partly supported by the Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red de Salud MentalS

Cognitive-behavioral intervention via interactive multimedia online video game for active aging: study protocol for a randomized controlled trial

Background Due to the progressive aging of the population, programs to promote active aging have been recommended. However, older adults have difficulty accessing them. Interventions administered through online video games may increase their accessibility, and complementing these with a smartphone app will likely increase adherence and allow for ongoing professional monitoring. The objective of this study is to evaluate the efficacy of a cognitive-behavioral intervention for active aging administered through an online interactive multimedia video game that includes a smartphone app companion. The secondary objectives are to analyze the moderators and mediators of the change in the outcome variables and to evaluate the adherence to the intervention. Methods/design A randomized controlled clinical trial will be conducted. Adults 45 years and older will be randomly assigned to a cognitive-behavioral intervention administered through an online multimedia video game that includes a smartphone app companion or to a control group that will receive online information on active aging (274 participants per group). The intervention will be administered in eight weekly 45-min modules. An investigator-blinded evaluation will be conducted using online self-administered tests at baseline, post-intervention, and 6- and 12-month follow-ups. The primary outcome will be mental health status as evaluated using the 36-item Short-Form Health Survey (SF-36) at post-intervention. Secondary outcomes will be emotional well-being, depressive symptoms, reinforcement, negative thoughts, self-reported memory, cognitive task performance, sleep hygiene behaviors, physical activity, eating habits, body mass index, social support, dropout, treatment adherence, and satisfaction with the intervention. Discussion If the results are favorable, this study would involve the development of the first evidence-based active aging promotion intervention based on a video game that includes a smartphone app companion, providing evidence on its efficacy, accessibility, and clinical utility.The development of this protocol was funded by grant EXP - 00091195/ ITC20161137 from Center for Industrial Technological Development of Spain and the European Regional Development Fund, and grant 2018-PU054 from Department of Culture, Education and University RegulationS

Can we predict psychostimulant use in youths? A study with structural equation modeling analysis

Conocer qué factores predicen el consumo de psicoestimulantes en jóvenes es importante para el diseño de programas preventivos y para identificar a los jóvenes que tienen una mayor probabilidad de consumir y así evitar que aparezcan los problemas derivados de dicho consumo. El objetivo de este estudio fue analizar la relación entre la disponibilidad percibida, la percepción de riesgo, los rasgos de personalidad, los patrones de personalidad antisocial y el consumo de otras sustancias en la predicción del consumo de psicoestimulantes. La muestra estuvo formada por 1.177 jóvenes (584 varones y 593 mujeres) de entre 14 y 25 años en España, reclutados aleatoriamente, estratificados por consumo-no consumo de psicoestimulantes (cocaína o éxtasis) alguna vez en la vida. El path que mejor predijo el consumo de psicoestimulantes fue: rasgos de personalidad-patrones de personalidad antisocial- consumo de psicoestimulantes. El siguiente path fue: rasgos de personalidad- patrones de personalidad antisocial-consumo de psicoestimulantes. La percepción de riesgo y la disponibilidad percibida fueron significativas en la predicción pero aportaron una contribución menor. Los resultados de este estudio sugieren que el modelo evaluado es adecuado para la predicción del consumo de psicoestimulantes en jóvenes. Este modelo puede ser de utilidad para desarrollar estrategias preventivas y para identificar a aquellos jóvenes con riesgo de tener problemas relacionados con el consumo de drogasKnowing which factors predict the use of psychostimulant drugs among youths is important for designing preventive programs and the identification of youths with the highest probability of use, to avoid some of the problems that can be derived from it. The purpose of this study is to examine the relationship between perceived availability, risk perception, personality traits, antisocial personality patterns, and use of other substances in the prediction of psychostimulant use. The sample was composed by 1,177 youths (584 males and 593 females) aged 14 to 25 in Spain, recruited randomly, stratified by lifetime use- non use of psychostimulants (cocaine or ecstasy). The path which best predicts psychostimulant use is: Personality traits-legal substance use-cannabis use-psychostimulant use. The next path is: Personality traits-antisocial personality patterns-psychostimulant use. Risk perception and perceived availability were significant in the prediction, but made a smaller contribution. The results of this study suggest that the model evaluated can predict psychostimulant use in youths. This model can be seen as a useful tool for developing preventive strategies and for identifying those youths that are at risk for problems related to drug useThis research was supported by Xunta de Galicia, Servicio Galego de Saúde (SERGAS) by a cooperation agreement between Xunta de Galicia-SERGAS and University of Santiago de Compostela, SpainS

Revealing the reporting disparity: VigiBase highlights underreporting of clozapine in other Western European countries compared to the UK

Background: Pharmacovigilance studies indicate clozapine history is marked by adverse drug reactions (ADRs). Objective: In a 2021 article, the United Kingdom (UK) had >90 % of European clozapine-related fatal outcomes in VigiBase, the World Health Organization's pharmacovigilance database. Two possibly opposing hypotheses could explain this disparity: 1) fewer reported fatal outcomes in other Western European countries mainly reflect underreporting to VigiBase, and 2) the higher number of UK reports reflects higher real relative mortality. Methods: VigiBase reports from clozapine's introduction to December 31, 2022, were studied for ADRs and the top 10 causes of fatal outcomes. The UK was compared with 11 other top reporting Western countries (Germany, Denmark, France, Finland, Ireland, Italy, Netherlands, Norway, Spain, Sweden and Switzerland). Nine countries (except Ireland and Switzerland) were compared after controlling for population and clozapine prescriptions. Results: The UK accounted for 29 % of worldwide clozapine-related fatal outcomes, Germany 2 % and <1 % in each of the other countries. The nonspecific label "death" was the top cause in the world (46 %) and in the UK (33 %). "Pneumonia" was second in the world (8 %), the UK (12 %), Ireland (8 %) and Finland (14 %). Assuming that our corrections for population and clozapine use are correct, other countries underreported only 1-10 % of the UK clozapine fatal outcome number. Conclusions: Different Western European countries consistently underreport to VigiBase compared to the UK, but have different reporting/publishing styles for clozapine-related ADRs/fatal outcomes. Three Scandinavian registries suggest lives are saved as clozapine use increases, but this cannot be studied in pharmacovigilance databases

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of lifeThis project was partially supported by Fundación Española de Farmacia Hospitalaria “Convocatoria de ayudas de proyectos para grupos de trabajo de la SEFH 2021-2022”, Plan Galego de Saude Mental (SERGAS) and Axencia Galega Innovación (Grupos de Potencial Crecimiento IN607B2020/11). Bandín-Vilar E.: Mondelo-García C. and Fernández-Ferreiro A. are grateful to the Carlos III Health Institute for financing their personnel contracts: CM20/00135, JR20/00026 and JR18/00014S

Do adolescents who use stimulants have a different personality?

El consumo de psicoestimulantes tiene una especial importancia en nuestro medio por su notable incremento entre los más jóvenes. El objetivo del presente estudio es determinar si hay diferencias entre menores de edad consumidores y no consumidores de psicoestimulantes (cocaína y éxtasis) en función de las características de personalidad evaluadas con el MACI. La muestra está formada por 398 jóvenes entre 14 y 17 años que fueron seleccionados con un muestreo aleatorio en los domicilios de los entrevistados y en lugares de ocio y diversión. Los resultados confirman la existencia de importantes diferencias en las características de personalidad de ambos. Los jóvenes que han consumido psicoestimulantes se caracterizan por tener los prototipos de personalidad Rebelde, Rudo, Oposicionista y Tendencia límiteStimulant consumption is especially important in our context because its use has greatly increased in recent years. The aim of the present study is to analyze the differences between stimulant users and nonusers (under 18 years old) in personality characteristics assessed with the MACI. The sample comprises 398 youths between 14 and 17 years old who were selected through random sampling in their homes or in recreational night spots. Results show important differences in personality features between stimulant users and nonusers. Stimulant users are characterized by having unruly, forceful, oppositional and borderline-tendency personality prototypesS

Drunkenness, driving and sexual relations in young cocaine and ecstasy users

Los accidentes de tráfico, las enfermedades de transmisión sexual y embarazos no deseados, las borracheras y el consumo de drogas (fundamentalmente psicoestimulantes) son algunos de los aspectos más negativos asociados al reciente fenómeno de salir de marcha. El objetivo del presente estudio es analizar en una muestra de 1214 jóvenes de 14 a 25 años (49.7% varones y 50.3% mujeres) si los consumidores de psicoestimulantes (cocaína y éxtasis) tienen mayor frecuencia de borracheras y de realización de conductas de riesgo en el ámbito de las relaciones sexuales y la conducción de vehículos y analizar el peso que estas conductas tienen para predecir los consumos de psicoestimulantes en el último año. Los resultados indican que los consumidores de psicoestimulantes se emborrachan con más frecuencia, es más probable que hayan visto a un familiar ebrio y tienen más conductas de riesgo relacionadas con la conducción y el mantenimiento de relaciones sexuales completas. Por lo tanto, los consumidores de cocaína y éxtasis son una población de riesgo a la que deben de ir dirigidas campañas de prevención específicas por el alto riesgo de las conductas que realizanTraffic accidents, sexually-transmitted diseases, unwanted pregnancies, drunkenness, and drug use (especially psychostimulants) are negative aspects associated with recreational nightlife. The aim of the present study is to analyze in a sample of 1214 young people (aged 15-25; 49.7% males, 50.3% females) whether psychostimulant users (cocaine and ecstasy) have a higher frequency of drunkenness and risk behaviours related to sex and to driving. We also analyze the importance of these behaviours in the prediction of psychostimulant use in the last year. The results indicate that psychostimulant users get drunk more frequently, are more likely to have seen a relative drunk, and present more risk behaviours in the contexts of driving and full sexual relations. Therefore, cocaine and ecstasy users are a risk population who need specific preventive programsS

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 phaseEsta 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 tratamientoS

Development and Validation of Predictive Model for a Diagnosis of First Episode Psychosis Using the Multinational EU-GEI Case-control Study and Modern Statistical Learning Methods

Background and Hypothesis: It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. Study Design: We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18-64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. Study Results: Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROC=0.84-0.86). Specificity (range=73.9-78.0%) and sensitivity (range=75.6-79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. Conclusions: The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability.</p