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.

Low risk of viral hepatitis amongst patients with severe mental disorders.

BACKGROUND AND AIMS: Patients with severe mental disorders (SMD) have been classically considered as a particularly high-risk population for bloodborne virus infections. We performed a systematic screening of hepatitis B and C virus among the population with SMD in the area of influence of Hospital Clínic (Barcelona) in order to evaluate the real prevalence of these infections and achieve HCV microelimination in this subpopulation. METHODS: We screened two cohorts for anti-HCV and HBsAg: Cohort A (hospitalized patients with SMD, done systematically) and Cohort B (outpatients, mental health centre-CSMA, done voluntarily). Risk factors and socio-demographic variables were collected. In positive cases, telematic review was activated by Hepatology, calculation of FIB-4 and prescription of direct-acting agents (DAA) in HCV or follow-up in HBV. RESULTS: In Cohort A, 404 patients were screened. 3 HBV patients were detected (0.7%). In all of them, there was a history of drug use. 12 anti-HCV positive patients were detected (3%); 8 of them had a history of drug use. Among the HCV positive, only 2 patients were viraemic (received DAA, both achieving SVR) as most of them (n = 6) had already been cured with DAA. In cohort B, 305 patients were screened, after 542 (64% of the target population) declined to participate. No cases of HCV or HBV were detected. CONCLUSIONS: HCV/HBV prevalence among SMD population with no history of drug use does not seem to be different from the general population. These data may be of interest for defining health policies.

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

The relationship between cognition and functioning in Bipolar Disorder: An investigation using functional imaging during working memory performance.

The psychosocial functioning of individuals suffering from bipolar disorder (BD) has a significant impact on prognosis and quality of life. The aim of this study was to assess brain functional correlates of psychosocial functioning in BD individuals during the performance of a working memory task. Sixty-two subjects (31 euthymic BD individuals and 31 matched healthy controls) underwent structural and functional magnetic resonance imaging scanning while performing the 1- and 2-back versions of the n-back task (1-back and 2-back). The Functional Assessment Short Test (FAST) and its subdomains were used to assess functioning. Whole brain analysis revealed only overall activation differences between BD patients and healthy controls, but the patients showed failure of de-activation in the medial frontal cortex. Six clusters of significant inverse correlation with the FAST scores were found in the dorsolateral prefrontal cortex, the superior parietal cortex, and temporo-occipital regions bilaterally, and in the left inferior frontal cortex. Cognitive and occupational functioning were the subdomains most significantly associated with brain activation in these clusters. The results suggest that poor psychosocial functioning in BD individuals is associated with hypoactivation in a range of cortical regions, including the fronto-parietal working memory network and inferior temporo-occipital regions.

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 / Clinical practice guideline on pharmacological and psychological management of adult patients with schizophrenia spectrum disorders and a comorbid substance use

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 Evaluation»).(AU)

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.(AU)

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 / Clinical practice guideline on pharmacological and psychological management of adult patients with depression and a comorbid substance use disorder

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.(AU)

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.(AU)

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 / Clinical practice guideline on pharmacological and psychological management of adult patients with bipolar disorder and comorbid substance use

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.(AU)

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.(AU)

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 / Clinical practice guideline on pharmacological and psychological management of adult patients with an anxiety disorder and comorbid substance use

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).(AU)

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 post-traumatic 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).(AU)

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 / Clinical practice guideline on pharmacological and psychological management of adult patients with attention deficit and hyperactivity disorder and comorbid substance use

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).(AU)

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).(AU)

Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

In vivo hippocampal subfield volumes in bipolar disorder-A mega-analysis from The Enhancing Neuro Imaging Genetics through Meta-Analysis Bipolar Disorder Working Group.

The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

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.

Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.

AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.

Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.

BACKGROUND: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. METHODS: Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. RESULTS: Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18

Cariprazine-induced mania: A case series report.

Bipolar depression is the most prevalent phase of bipolar disorder (BD). There is a risk of inducing treatment-emergent affective switches (TEAS) with antidepressants (ADs). Hence, clinical guidelines do not recommend their use in monotherapy. Cariprazine is a dopamine-serotonin partial agonist, with a recent FDA approval as a monotherapy for BD type 1 (BD-I) depression. To our knowledge, there is no significant evidence of cariprazine-induced TEAS in bipolar depression. We describe three clinical cases of patients admitted to our acute psychiatric ward who developed manic episodes after the introduction of low doses of cariprazine. Two of the patients met the DSM-5 criteria for BD-I, and one for schizoaffective disorder, bipolar type. All patients were initially treated with low doses of cariprazine (1.5 mg) during a depressive phase. All three cases were simultaneously treated with mood stabilizers, regardless of which they switched to a manic episode when cariprazine was initiated. In our review of previous studies assessing the efficacy and side effects profile of cariprazine in BD-I, TEAS have not been found to be significant. However, according to our experience, cariprazine may induce affective switches in BD-I patients. Patients and psychiatrists should receive information regarding early warning symptoms and monitor possible cariprazine-induced mood switching.

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.

Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.

Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles  and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.