Valbenazine has a small but meaningful benefit for tardive dyskinesia

A critical appraisal and clinical application of Hauser RA, Factor SA, Marder SR, et al. KINECT 3: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Valbenazine for Tardive Dyskinesia. Am J Psychiatry. 2017;174(5):476-484. https://doi.org/10.1176/appi.ajp.2017.16091037 and Factor SA, Remington G, Comella CL, et al. The Effects of Valbenazine in Participants with Tardive Dyskinesia: Results of the 1-Year KINECT 3 Extension Study. J Clin Psychiatry. 2017;78(9):1344-1350. https://doi.org/10.4088/JCP.17m11777 exploring the efficacy of a newer therapy for tardive dyskinesia, and describing recommendations for a patient with acute medical problems and longstanding tardive dyskinesia.

The epigenetic modulation of alcohol/ethanol and cannabis exposure/co-exposure during different stages

Studies have reported the significant economic impact of smoking cannabis and drinking alcohol In the USA. It was estimated that the costs of cannabis-related treatment, hospitalization and loss of work-related pay have amounted to $200 billion. (Andersen AM, Dogan MV, Beach SRH, Philibert RA. 2015 Genes 6 , 991–1022. ( doi:10.3390/genes6040991 )). Data from the National Epidemiologic Survey on Alcohol and Related Conditions showed that individuals with general anxiety disorder and substance use disorder (GAD-SUD) have higher psychiatric comorbidity rates than those without substance use disorder (Alegría AA, Hasin DS, Nunes EV, Liu SM, Davies C, Grant BF, Blanco C. 2010 J. Clin. Psychiatry 71, 1187–1195. ( doi:10.4088/JCP.09m05328gry )). Moreover, the criminal justice system is significantly impacted by this cost (Andersen AM, Dogan MV, Beach SRH, Philibert RA. 2015 Genes 6 , 991–1022. ( doi:10.3390/genes6040991 )). Despite the increasing use of cannabis, there are still too many obscure facts. One of the new areas that scientific evidence shows is impacted negatively by cannabis use is the epigenome, which is an understudied area that we are still learning about. In addition, over the past few decades, we have seen various social and healthcare changes that have raised critical questions about their ongoing roles in regulating marijuana and alcohol use. This is important because of the increasing popularity and usage across various ages especially young adults and teenagers. More than 97.5 million Americans over 12 years old have used cannabis for non-medical use despite the significant side effects, with 1 in 10 users developing cannabis dependence (Crean RD, Crane NA, Mason BJ. 2011 J. Addict. Med. 5, 1–8. ( doi:10.1097/ADM.0b013e31820c23fa ), Office of Applied Studies. 2006 Substance Abuse and Mental Health Services Administration, USA.). It was reported that 16% of substance abuse admissions in the USA were for cannabis-related symptoms, which is second only to alcohol-related disorders (Agalioti T, Lomvardas S, Parekh B, Yie J, Maniatis T, Thanos D. 2000 Cell 103, 667–678. ( doi:10.1016/S0092-8674(00)00169-0 ), Soutoglou E, Talianidis I. 2002 Science 295, 1901–1904. ( doi:10.1126/science.1068356 )). Today there are thirty-one states and the District of Columbia that currently have legalized marijuana for either medical or recreational use. Data about marijuana use from NIAAA's National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) indicates that ‘in total, 79 000 people were interviewed on alcohol and drug use. When examined by age young adults (ages 18–21) were found to be at highest risk for marijuana use and marijuana use disorder, with use increasing from 10.5 to 21.2% and disorder increasing from 4.4 to 7.5%’. ‘Given these facts, George Koob, PhD, director of NIAAA stated the importance for the scientific community to convey this information to the public about the potential hazards of marijuana and it's use’. On the other hand, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from alcohol use disorders. To the best of our knowledge, epigenetic mechanisms have been previously studied in alcohol and cannabis abuse separately. Recent studies highlighted the molecular mechanisms that are linked with drug-induced transcriptional regulation, behavioural abnormalities and neurodegeneration, which has emphasized the role of chromatin modification/remodelling in the generation of drug activation of certain genes and the disabling of others, and the effect of that on addiction (Maze I, Nestler EJ. 2011 Ann. N. Y. Acad. Sci. 1216, 99–113. ( doi:10.1111/j.1749-6632.2010.05893.x ); Renthal W, Nestler EJ. 2008 Trends Mol. Med . 14, 341–350. ( doi:10.1016/j.molmed.2008.06.004 )). In this review, we will give an overview of epigenome science relevant to cannabis/the endocannabinoid system and the potential of epigenetic overlap between alcohol and cannabinergic activity at different stages, to aid further investigations that could bring more treatment options to our horizon.

Vers une définition actualisée de la dépression résistante

La dépression unipolaire est une maladie fréquente et particulièrement sévère en termes de morbi-mortalité (prévisions OMS pour 2030). Cette sévérité est en partie liée au profil évolutif de la maladie et en particulier au caractère de résistance aux traitements antidépresseurs qu’elle peut comporter. On estime ainsi que la résistance peut atteindre jusqu’à 30 % des cas de dépression unipolaire (Thase, J Clin Psychiatry, 2011). Une prise en charge optimale des dépressions résistantes est donc indispensable mais nécessite au préalable une définition claire, consensuelle et utilisable en clinique. La définition de la résistance la plus utilisée prend en compte uniquement le nombre d’essais d’antidépresseurs (Thase, J Clin Psychiatry, 1997, 1998). Elle présente l’avantage de la simplicité mais comporte plusieurs limites. Il apparaît aujourd’hui nécessaire pour bien définir la résistance d’une dépression de déterminer les facteurs prédictifs cliniques et para-cliniques, le profil évolutif de la maladie, ainsi que le niveau de résistance actuel tout en ayant pris soin d’éliminer une pseudo-résistance. Cette notion de résistance s’inscrit ainsi complètement dans l’évolution du cours de la maladie et est caractérisée par son intensité et sa dynamique. Cette définition théorique peut permettre en la transposant à la pratique clinique de dégager une prise en charge adaptée, personnalisée et, de là, plus efficace pour chaque patient. Néanmoins, ce travail de définition et de suivi de la résistance n’est pas aisé dans la pratique clinique courante et le développement d’outils cliniques spécifiques allant au-delà de la simple quantification de la résistance pourrait faciliter cette démarche, ainsi que le recours à des centres spécialisés dédiés à cette problématique.

Diagnóstico de la hipomanía basado en el número de síntomas no prioritarios: un reto a los criterios del DSM-IV

ResumenAntecedentes.La definición del DSM-IV de la hipomanía del trastorno bipolar II (TBP-II), que incluye el cambio a un estado de ánimo elevado/irritable como rasgo central (es decir, que debe estar presente siempre), no se basa en datos sólidos.Propósito del estudio.Siguiendo las descripciones clásicas de la hipomanía, el propósito era comprobar si se podía diagnosticar hipomanía a partir de su número de síntomas del DSM-IV (9) sin establecer síntomas prioritarios.Métodos.Un psiquiatra especialista en estado de ánimo reentrevistó a 422 pacientes ambulatorios consecutivos con depresión en remisión utilizando la Entrevista Clínica Estructurada para los Trastornos del Eje I del DSM-IV, versión del profesional clínico [una entrevista semiestructurada modificada por Benazzi y Akiskal (J. Affect. Disord, 2003; J. Clin. Psychiatry, 2005) para mejorar la búsqueda del TBP-II], en una consulta privada. Se evaluó sistemáticamente la historia de episodios de hipomanía subumbral (es decir, 2 o más síntomas) y umbral (es decir, cumplir los criterios del DSM-IV de estado de ánimo elevado más 3 síntomas al menos, o estado de ánimo irritable más 4 síntomas al menos), con una duración de 2 días como mínimo y cuáles eran los sintomas más comunes durante los episodios.Resultados.Los pacientes con trastorno bipolar II (TBP-II) (según los criterios del DSM-IV, aparte de la duración de la hipomanía) eran 260 y los pacientes con trastorno depresivo mayor (TDM) eran 162. El cambio de estado de ánimo estaba presente en todos los TBPII por definición. Los síntomas más comunes eran la actividad excesiva, que estaba presente en casi todos los pacientes con TBP-II, seguido por elevación del estado de ánimo y aceleración del pensamiento. El análisis de la COR del número de síntomas hipomaníacos que predecía TBP-II encontró que un punto de corte de 5 o más síntomas sobre 9 tenía la mejor combinación de sensibilidad (90%) y especificidad (84%) y la cifra más alta de TBP-II clasificados correctamente (87%). Casi todos los pacientes con TBP-II tenían antecedentes de episodios de 5 o más síntomas hipomaníacos.Limitaciones.Un único entrevistador.Conclusiones.Siguiendo las descripciones clásicas de la hipomanía y sin establecer ninguna prioridad entre los tres dominios básicos de ésta (estado de ánimo, pensamiento y conducta), los resultados indican que se podría utilizar un número de corte de 5 síntomas sobre 9 (de los enumerados por el DSM-IV) para diagnosticar la hipomanía del TBP-II. Diagnosticar la hipomanía contando una lista de síntomas debería hacer más sencillo el diagnóstico del TBP-II, y debería reducir el elevado diagnóstico erróneo actual del TBP-II como TDM, que tiene un impacto significativo en el tratamiento de la depresión.

Challenging DSM-IV criteria for hypomania: Diagnosing based on number of no-priority symptoms

BackgroundDSM-IV definition of hypomania of bipolar-II disorder (BP-II), which includes elevated/irritable mood change as core feature (i.e., it must always be present), is not based on sound evidence.Study aimFollowing classic descriptions of hypomania, was to test if hypomania could be diagnosed on the basis of its number (9) of DSM-IV symptoms, setting no-priority symptom.MethodsConsecutive 422 depression-remitted outpatients were re-interviewed by a mood specialist psychiatrist using the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version [a semi-structured interview modified by Benazzi and Akiskal (J Affect Disord, 2003; J Clin Psychiatry, 2005) to improve the probing for BP-II] in a private practice. History of episodes of subthreshold (i.e., 2 or more symptoms) and threshold (i.e., meeting DSM-IV criteria of elevated mood plus at least 3 symptoms, or irritable mood plus at least 4) hypomania, lasting at least 2 days, and which were the most common symptoms during the episodes, were systematically assessed.ResultsBipolar-II disorder (BP-II) patients (according to DSM-IV criteria, apart from hypomania duration) were 260, and major depressive disorder (MDD) patients were 162. Mood change was present in all BP-II by definition. The most common symptoms were overactivity, which was present in almost all BP-II, followed by elevated mood and racing thoughts. ROC analysis of the number of hypomanic symptoms predicting BP-II found that a cut point of 5 or more symptoms over 9 had the best combination of sensitivity (90%) and specificity (84%), and the highest figure of correctly classified (87%) BP-II. History of episodes of 5 or more hypomanic symptoms was met by almost all BP-II.LimitationsSingle interviewer.ConclusionsFollowing classic descriptions of hypomania, not setting any priority among the three basic domains of hypomania (mood, thinking, behavior), results suggest that a cutoff number of 5 symptoms over 9 (of those listed by DSM-IV) could be used to diagnose hypomania of BP-II. Diagnosing hypomania by counting a checklist of symptoms should make it easier to diagnose BP-II, and should reduce the current high misdiagnosis of BP-II as MDD, significantly impacting the treatment of depression.