Mise au point de mesures de variables intermédiaires pour les essais cliniques dans la dépendance à la cocaïne (craving et symptômes psychotiques)

La dépendance à la cocaïne est un problème de santé publique d importance croissante. Il n existe pas actuellement de traitement pharmacologique validé dans la dépendance à la cocaïne. Les essais thérapeutiques nécessitent une méthodologie qui permette d évaluer l efficacité des médicaments employés. Il n existait pas à ce jour de mesure d efficacité des traitements pharmacologiques dans la dépendance à la cocaïne validée en français. Nous avons mis au point et validé des questionnaires pouvant servir de mesures intermédiaires d efficacité pour les essais pharmacologiques dans la dépendance à la cocaïne. Nous avons choisi de nous intéresser à deux types de variables intermédiaires : le craving et les symptômes psychotiques. Le craving est le besoin impérieux de reconsommer une drogue. Ce concept psychologique est un marqueur de dépendance. Nous avons conçu un questionnaire de craving en langue française : l OCCS (Obsessive Compulsive Cocaïne Scale), en nous basant sur les travaux de plusieurs équipes travaillant dans le domaine de la dépendance à l alcool. Nous avons validé ce questionnaire sur une population de 119 sujets cocaïnomanes suivis en centre de soins (Vorspan et al 2012). Nous avons notamment montré que les scores à ce questionnaire étaient corrélés à une mesure de craving par échelle visuelle analogique, étaient supérieurs chez les sujets dépendants par rapport aux sujets abuseurs de cocaïne, et étaient sensible au changement. Nous avons déjà utilisé le questionnaire de craving OCCS dans un essai thérapeutique en ouvert d aripiprazole chez 10 patients dépendants du crack non schizophrènes (Vorspan et al 2008). Nous proposons également de l utiliser pour évaluer l efficacité d interventions non pharmacologiques dans la dépendance à la cocaïne, comme la stimulation cérébrale profonde (Vorspan et al 2011), ou des interventions psychothérapeutiques. Les symptômes psychotiques se composent de différentes manifestations (hallucinations, idées délirantes et modifications comportementales). Nous avons choisi d adapter en français un questionnaire évaluant les symptômes psychotiques transitoires survenant dans les quelques minutes à quelques heures suivant une consommation de cocaïne : le SAPS-CIP (Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis). Nous avons montré que ces symptômes sont fréquents mais d intensité variable dans une population de patients cocaïnomanes suivis en centre de soins (Vorspan et al, soumis), et qu ils étaient sensibles au changement (Vorspan et al 2011). Il existe des hypothèses de vulnérabilité génétique à la survenue des symptômes psychotiques lors de l usage de cocaïne. La vulnérabilité à cette complication pourrait être un facteur de protection vis-à-vis de l acquisition d une dépendance à la cocaïne (Brousse et al 2010). La mesure des symptômes psychotiques survenant lors de l usage de drogue permet de modéliser une vulnérabilité pharmacogénétique vis-à-vis des addictions. Nous proposons d utiliser ces deux mesures (OCCS pour le craving et SAPS-CIP pour les symptômes psychotiques) dans les essais thérapeutiques dans la dépendance à la cocaïne. En effet, il paraît pertinent, au regard des particularités cliniques de la dépendance à la cocaïne, de viser une réduction ou une disparition de ces deux ordres de symptômes. Une diminution du craving pourrait constituer une variable intermédiaire de l objectif final d obtenir une abstinence de la drogue. Une diminution des symptômes psychotiques pourrait constituer un moyen de réduction de la morbi-mortalité liée à l usage de cocaïne.Cocaine dependence is a growing public health concern in France. There is no pharmacological treatment validated for cocaine dependence treatment. Clinical trials require that validated methods are used to ascertain the efficacy of new drugs that are tested. There was no validated tool available to conduct pharmacological trials for cocaine dependence in French. We conceptualized and validated questionnaires that could be used as surrogate endpoints in pharmacological trials for cocaine dependence. We choose to work on two types of surrogate variables: craving and psychotic symptoms.Craving is the overwhelming desire to use a drug. It is a psychological construct that can be used as a biomarker of dependence. We designed a craving questionnaire in French named OCCS (Obsessive Compulsive Cocaïne Scale) after the work of several research teams working in the field of alcohol dependence. We validated this questionnaire in a sample of 119 cocaine addicts in a clinical setting (Vorspan et al 2012). We could demonstrate that the scores obtained on this questionnaire were correlated to those obtain on a visual analogue scale of craving. We could also demonstrate that the scores were higher in cocaine dependent that in cocaine abusing subjects. Lastly, we could demonstrate that the scores were time-sensitive. We used this questionnaire OCCS in an open-label trial of aripiprazole in 10 non-schizophrenic crack dependent patients (Vorspan et al 2008). We propose that this questionnaire could be used in clinical trials assessing the efficacy of various therapeutic interventions in cocaine dependent subjects, pharmacological treatments, but also deep brain stimulation (Vorspan et al 2011) and psychological interventions. Psychotic symptoms are composed of various phenomenons (hallucinations, delusions and behavioural modifications). We choose to adapt in French a validated questionnaire that assesses psychotic symptoms occurring between a few minutes to a few hours after cocaine intake: the SAPS-CIP (Scale for Assessment of Positive Symptoms for Cocaine-Induced Psychosis). We could demonstrate that those symptoms are frequent but of variable intensity in a sample of French cocaine addicts in a clinical setting (Vorspan et al, soumis). We could also demonstrate that those symptoms are change sensitive (Vorspan et al 2011). We hypothesized that there is a genetic vulnerability to cocaine-induced psychotic symptoms, and that being sensitive to the occurrence of psychotic symptoms could be a protective factor toward the development of cocaine dependence (Brousse et al 2010). The variability of cocaine-induced psychotic symptoms helps to conceptualize a pharmacogenetic model of drug dependence. We propose that those two questionnaires (OCCS for craving and SAPS-CIP for psychotic symptoms) could be used in clinical trial in cocaine dependent subjects. It seems very helpful indeed, knowing the clinical pattern of cocaine dependence, to design trails aimed at reducing or suppressing craving and psychotic symptoms. Reducing or suppressing craving could be a surrogate endpoint for cocaine abstinence. Reducing or suppressing cocaine-induced psychotic symptoms could reduce the morbidity and mortality associated with cocaine use.PARIS5-Bibliotheque electronique (751069902) / SudocPARIS-BIUM-Bib. électronique (751069903) / SudocSudocFranceF

Association of Childhood Adversities and Early-Onset Mental Disorders With Adult-Onset Chronic Physical Conditions

Context: The physical health consequences of childhood psychosocial adversities may be as substantial as the mental health consequences, but whether this is the case remains unclear because much prior research has involved unrepresentative samples and a selective focus on particular adversities or physical outcomes. The association between early-onset mental disorders and subsequent poor physical health in adulthood has not been investigated. Objective: To investigate whether childhood adversities and early-onset mental disorders are independently associated with increased risk of a range of adult-onset chronic physical conditions in culturally diverse samples spanning the full adult age range. Design: Cross-sectional community surveys of adults in 10 countries. Setting: General population. Participants: Adults (ie, aged >= 18 years; N=18 303), with diagnostic assessment and determination of age at onset of DSM-IV mental disorders, assessment of childhood familial adversities, and age of diagnosis or onset of chronic physical conditions. Main Outcome Measures: Risk (ie, hazard ratios) of adult-onset (ie, at age > 20 years) heart disease, asthma, diabetes mellitus, arthritis, chronic spinal pain, and chronic headache as a function of specific childhood adversities and early-onset (ie, at age <21 years) DSM-IV depressive and anxiety disorders, with mutual adjustment. Results: A history of 3 or more childhood adversities was independently associated with onset of all 6 physical conditions (hazard ratios, 1.44 to 2.19). Controlling for current mental disorder made little difference to these associations. Early-onset mental disorders were independently associated with onset of 5 physical conditions (hazard ratios, 1.43 to 1.66). Conclusions: These results are consistent with the hypothesis that childhood adversities and early-onset mental disorders have independent, broad-spectrum effects that increase the risk of diverse chronic physical conditions in later life. They require confirmation in a prospectively designed study. The long course of these associations has theoretical and research implications

Development of lifetime comorbidity in the world health organization world mental health surveys

CONTEXT: Although numerous studies have examined the role of latent variables in the structure of comorbidity among mental disorders, none has examined their role in the development of comorbidity. OBJECTIVE: To study the role of latent variables in the development of comorbidity among 18 lifetime DSM-IV disorders in the World Health Organization World Mental Health Surveys. DESIGN: Nationally or regionally representative community surveys. SETTING: Fourteen countries. PARTICIPANTS: A total of 21 229 survey respondents. MAIN OUTCOME MEASURES: First onset of 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders assessed retrospectively in the World Health Organization Composite International Diagnostic Interview. RESULTS: Separate internalizing (anxiety and mood disorders) and externalizing (behavior and substance disorders) factors were found in exploratory factor analysis of lifetime disorders. Consistently significant positive time-lagged associations were found in survival analyses for virtually all temporally primary lifetime disorders predicting subsequent onset of other disorders. Within-domain (ie, internalizing or externalizing) associations were generally stronger than between-domain associations. Most time-lagged associations were explained by a model that assumed the existence of mediating latent internalizing and externalizing variables. Specific phobia and obsessive-compulsive disorder (internalizing) and hyperactivity and oppositional defiant disorders (externalizing) were the most important predictors. A small number of residual associations remained significant after controlling the latent variables. CONCLUSIONS: The good fit of the latent variable model suggests that common causal pathways account for most of the comorbidity among the disorders considered herein. These common pathways should be the focus of future research on the development of comorbidity, although several important pairwise associations that cannot be accounted for by latent variables also exist that warrant further focused study

L’irruzione dei sentimenti nel canto popolare. Un capitolo di storia sociale del matrimonio

Viene seguito il mutamento storico degli atteggiamenti popolari verso corteggiamento, fidanzamento e matrimonio, e più in generale verso i sentimenti, attraverso l'analisi e il commento di canti popolari italiani, fonte importante per lo studio della storia sociale

Psychotic Experiences in the General Population: A Cross-National Analysis Based on 31,261 Respondents From 18 Countries

IMPORTANCE: Community-based surveys find that many otherwise healthy individuals report histories of hallucinations and delusions. To date, most studies have focused on the overall lifetime prevalence of any of these psychotic experiences (PEs), which might mask important features related to the types and frequencies of PEs. OBJECTIVE: To explore detailed epidemiologic information about PEs in a large multinational sample. DESIGN, SETTING, AND PARTICIPANTS: We obtained data from the World Health Organization World Mental Health Surveys, a coordinated set of community epidemiologic surveys of the prevalence and correlates of mental disorders in representative household samples from 18 countries throughout the world, from 2001 through 2009. Respondents included 31,261 adults (18 years and older) who were asked about lifetime and 12-month prevalence and frequency of 6 types of PEs (2 hallucinatory experiences and 4 delusional experiences). We analyzed the data from March 2014 through January 2015. MAIN OUTCOMES AND MEASURES: Prevalence, frequency, and correlates of PEs. RESULTS: Mean lifetime prevalence (SE) of ever having a PE was 5.8% (0.2%), with hallucinatory experiences (5.2% [0.2%]) much more common than delusional experiences (1.3% [0.1%]). More than two-thirds (72.0%) of respondents with lifetime PEs reported experiencing only 1 type. Psychotic experiences were typically infrequent, with 32.2% of respondents with lifetime PEs reporting only 1 occurrence and 31.8% reporting only 2 to 5 occurrences. We found a significant relationship between having more than 1 type of PE and having more frequent PE episodes (Cochran-Armitage z = -10.0; P < .001). Lifetime prevalence estimates (SEs) were significantly higher among respondents in middle- and high-income countries than among those in low-income countries (7.2% [0.4%], 6.8% [0.3%], and 3.2% [0.3%], respectively; χ²₂ range, 7.1-58.2; P < .001 for each) and among women than among men (6.6% [0.2%] vs 5.0% [0.3%]; χ²₁ = 16.0; P < .001). We found significant associations with lifetime prevalence of PEs in the multivariate model among nonmarried compared with married respondents (χ²₂ = 23.2; P < .001) and among respondents who were not employed (χ²₄= 10.6; P < .001) and who had low family incomes (χ²₃ = 16.9; P < .001). CONCLUSIONS AND RELEVANCE: The epidemiologic features of PEs are more nuanced than previously thought. Research is needed that focuses on similarities and differences in the predictors of the onset, course, and consequences of distinct PEs

Understanding the prescription of antidepressants: a Qualitative study among French GPs

<p>Abstract</p> <p>Background</p> <p>One-tenth of France's population is prescribed at least one antidepressant, primarily by General Practitioners. The reasons for this high prescription rate remain unclear. One-third of these prescriptions may not comply with clinical practice guidelines, and 20% are potentially unrelated to any psychiatric condition. Our aim was to explore how GPs declare they use antidepressants in daily practice and understand their reasons for prescribing them.</p> <p>Method</p> <p>Six focus groups including a total of 56 rural and urban GPs, with four interviews were performed. The topic guide focused on reasons for prescribing antidepressants in various primary care situations. Phenomenological analysis was performed by four researchers.</p> <p>Results</p> <p>Antidepressants were seen as useful and not harmful. Personal assessment based on experience and feeling determined the GPs' decisions rather than the use of scales. Twenty-four "non-psychiatric" conditions possibly leading to prescription of antidepressants in primary care were found.</p> <p>Conclusions</p> <p>The GPs reported prescribing antidepressants for a wide range of conditions other than depression. The GPs' decision making process is difficult and complex. They seemed to prefer to focus on their difficulties in diagnosing depression rather than on useless overtreatment. Instead of using the guidelines criteria to detect potential cases of useful prescription, physicians tend to use their own tools based on gut feelings, knowledge of the patient and contextual issues.</p

A comparison of DSM-5 and DSM-IV agoraphobia in the World Mental Health Surveys

The Diagnostic and Statistical Manual of Mental Disorders, version 5 (DSM-5) definition of agoraphobia (AG) as an independent diagnostic entity makes it timely to re-examine the epidemiology of AG. Study objective was to present representative data on the characteristics of individuals who meet DSM-IV criteria for AG (AG without a history of panic disorder [PD] and PD with AG) but not DSM-5 criteria, DSM-5 but not DSM-IV criteria, or both sets of criteria.Population-based surveys from the World Mental Health Survey Initiative including adult respondents (n = 136,357) from 27 countries across the world. The Composite International Diagnostic Interview was used to assess AG and other disorders.Lifetime and 12-month prevalence estimates of DSM-5 AG (1.5% and 1.0%) were comparable to DSM-IV (1.4% and 0.9%). Of respondents meeting criteria in either system, 57.1% met criteria in both, while 24.2% met criteria for DSM-5 only and 18.8% for DSM-IV only. Severe role impairment due to AG was reported by a lower proportion of respondents who met criteria only for DSM-IV AG (30.4%) than those with both DSM-5 and DSM-IV AG (44.0%; χ  = 4.7; P = 0.031). The proportion of cases with any comorbidity was lower among respondents who met criteria only for DSM-IV AG (78.7%) than those who met both sets (92.9%; χ = 14.5; P

findings from the World Health Organization World Mental Health surveys

Funding Information: The World Health Organization World Mental Health (WMH) Survey Initiative is supported by the United States National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the United States Public Health Service (R13-MH066849, R01-MH069864 and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, Eli Lilly and Company, Ortho-McNeil Pharmaceutical Inc., GlaxoSmithKline and Bristol-Myers Squibb. We thank the staff of the WMH Data Collection and Data Analysis Coordination Centres for assistance with instrumentation, fieldwork and consultation on data analysis. The Argentina survey—Estudio Argentino de Epidemiología en Salud Mental (EASM)— was supported by a grant from the Argentinian Ministry of Health (Ministerio de Salud de la Nación). The São Paulo Megacity Mental Health Survey is supported by the State of São Paulo Research Foundation (FAPESP) Thematic Project Grant 03/00204–3. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The ESEMeD surveys were funded by the European Commission (contracts QLG5–1999-01042; SANCO 2004123 and EAHC 20081308), the Piedmont Region, Italy, Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnología, Spain (SAF 2000– 158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP) and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. Implementation of the Iraq Mental Health Survey (IMHS) and data entry were carried out by the staff of the Iraqi MOH and MOP with direct support from the Iraqi IMHS team with funding from both the Japanese and European Funds through the United Nations Development Group Iraq Trust Fund (UNDG ITF). The Lebanese Evaluation of the Burden of Ailments and Needs of the Nation (L.E.B.A.N.O.N.) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), National Institute of Health/Fogarty International Center (R03 TW006481–01), anonymous private donations to IDRAAC, Lebanon and unrestricted grants from, Algorithm, AstraZeneca, Benta, Bella Pharma, Eli Lilly, Glaxo Smith Kline, Lundbeck, Novartis, OmniPharma, Pfizer, Phenicia, Servier, UPO. The Mexican National Comorbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H), with supplemental support from the PanAmerican Health Organization (PAHO). Te Rau Hinengaro: the New Zealand Mental Health Survey (NZMHS) is supported by the New Zealand Ministry of Health, Alcohol Advisory Council and the Health Research Council. The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria) and the Federal Ministry of Health, Abuja, Nigeria. The Peruvian World Mental Health Study was funded by the National Institute of Health of the Ministry of Health of Peru. The Portuguese Mental Health Study was carried out by the Department of Mental Health, Faculty of Medical Sciences, NOVA University of Lisbon, with collaboration of the Portuguese Catholic University, and was funded by Champalimaud Foundation, Gulbenkian Foundation, Foundation for Science and Technology (FCT) and Ministry of Health. The Romania WMH study projects ‘Policies in Mental Health Area’ and ‘National Study regarding Mental Health and Services Use’ were carried out by the National School of Public Health and Health Services Management (former National Institute for Research and Development in Health, present National School of Public Health Management and Professional Development, Bucharest), with technical support of Metro Media Transilvania, the National Institute of Statistics—National Centre for Training in Statistics, SC. Cheyenne Services SRL, Statistics Netherlands and were funded by the Ministry of Public Health (former Ministry of Health) with supplemental support of Eli Lilly Romania SRL. The US National Comorbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; grant 044708) and the John W. Alden Trust. None of the funders had any role in the design, analysis, interpretation of results or preparation of this paper. The views and opinions expressed in this report are those of the authors and should not be construed to represent the views of the World Health Organization, other sponsoring organizations, agencies or governments. J.J.M. received the John Cade Fellowship APP1056929 from the National Health and Medical Research Council and the Niels Bohr Professorship from the Danish National Research Foundation. A complete list of all within-country and cross-national WMH publications can be found at http://www.hcp.med. harvard.edu/wmh/. Publisher Copyright: © 2017 Society for the Study of AddictionBackground and aims: Prior research has found bidirectional associations between psychotic experiences (PEs) and selected substance use disorders. We aimed to extend this research by examining the bidirectional association between PEs and various types of substance use (SU) and substance use disorders (SUDs), and the influence of antecedent mental disorders on these associations. Design, setting, participants and measurements: We used data from the World Health Organization World Mental Health surveys. A total of 30 902 adult respondents across 18 countries were assessed for (a) six types of life-time PEs, (b) a range of types of SU and DSM-IV SUDs and (c) mental disorders using the Composite International Diagnostic Interview. Discrete-time survival analyses based on retrospective age-at-onset reports examined the bidirectional associations between PEs and SU/SUDs controlling for antecedent mental disorders. Findings: After adjusting for demographics, comorbid SU/SUDs and antecedent mental disorders, those with prior alcohol use disorders [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2–2.0], extra-medical prescription drug use (OR = 1.5, 95% CI = 1.1–1.9), alcohol use (OR = 1.4, 95% CI = 1.1–1.7) and tobacco use (OR = 1.3, 95% CI = 1.0–1.8) had increased odds of subsequent first onset of PEs. In contrast, those with temporally prior PEs had increased odds of subsequent onset of tobacco use (OR = 1.5, 95% CI = 1.2–1.9), alcohol use (OR = 1.3, 95% CI = 1.1–1.6) or cannabis use (OR = 1.3, 95% CI = 1.0–1.5) as well as of all substance use disorders (ORs ranged between 1.4 and 1.5). There was a dose response relationship between both count and frequency of PEs and increased subsequent odds of selected SU/SUDs. Conclusions: Associations between psychotic experiences (PEs) and substance use/substance use disorders (SU/SUDs) are often bidirectional, but not all types of SU/SUDs are associated with PEs. These findings suggest that it is important to be aware of the presence of PEs within those with SUDs or at risk of SUDs, given the plausibility that they may each impact upon the other.publishersversionpublishe