Search

International audience; Introduction: Suicide attempts have been associated with both cocaine use disorder (CocUD) and childhood trauma. We investigated how childhood trauma is an independent risk factor for serious and recurrent suicide attempts in CocUD. Method: 298 outpatients (23% women) with CocUD underwent standardized assessments of substance dependence (Diagnostic and Statistical Manual-mental disorders, fourth edition, text revised), impulsiveness, resilience, and childhood trauma, using validated tools. Suicide attempts history was categorized as single vs. recurrent or non-serious vs. serious depending on the lifetime number of suicide attempts and the potential or actual lethality of the worst attempt reported, respectively. Bivariate and multinomial regression analyses were used to characterize which childhood trauma patterns were associated with the suicide attempts groups. Results: 58% of CocUD patients reported childhood trauma. Recurrent and serious suicide attempts clustered together and were thus combined into "severe SA." Severe suicide attempt risk increased proportionally to the number of childhood traumas (test for trend, p = 9 × 10-7). Non-severe suicide attempt risk increased with impulsiveness and decreased with resilience. In multinomial regression models, a higher number of traumas and emotional abuse were independently and only associated with severe vs. non-severe suicide attempts (effect size = 0.82, AUC = 0.7). The study was limited by its cross-sectional design. Conclusion: These preferential associations between childhood trauma and severe suicide attempts warrant specific monitoring of suicide attempts risk in CocUD, regardless of the severity of addiction profiles.

Cocaine-induced transient hallucinations (CIH) are a frequent complication following cocaine intake that is associated with addiction severity.Two hundred and forty-two non-psychotic and Caucasian lifetime cocaine users were included in a French multicentric study. Clinical variables and dopamine pathway genotype data were extracted and tested with CIH scores using a zero-inflated binomial model, which allows for the exploration of factors associated with occurrence and severity separately.Cocaine dependence (pOur study shows that CIH occurrence and severity are two distinct phenotypes, with shared clinical risk factors; however, they likely do not share the same genetic background.

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. We used data from the World Health Organisation World Mental Health surveys. A total of 30,902 adult respondents across 18 countries were assessed for (a) six types of lifetime 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. After adjusting for demographics, comorbid SU/SUDs and antecedent mental disorders, those with prior alcohol use disorders (OR=1.6, 95% 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. 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.

High-dose baclofen is prescribed as a maintenance treatment to reduce alcohol use in patients with alcohol use disorder. Nevertheless, some patients still have massive alcohol intakes and require inpatient alcohol withdrawal. To compare the oral dose of benzodiazepine prescribed to manage alcohol withdrawal symptoms in patients with vs. without steady-state pretreatment with high-dose baclofen. Retrospective chart review study. Prescribed benzodiazepine dose expressed in diazepam-equivalent was compared between groups. Thirty-one patients were assessed in the high-dose maintenance baclofen group and compared to 31 matched patients not receiving baclofen. No statistically significant difference was evident between groups regarding levels of benzodiazepines prescribed. The mean diazepam-equivalent dose during the first 7 days was 294 ± 149 mg in the baclofen group vs. 310 ± 133 mg (t-test = 0.440, P = 0.661) in matched controls. Steady-state high-dose baclofen before an inpatient alcohol cessation hospitalization does not lower the needed benzodiazepine dose in the management of alcohol withdrawal symptoms.

Background Suicide is a major public health concern and suicide attempts (SA) are frequent and burdensome in people suffering from substance use disorders (SUDs). In particular, serious SAs are a preoccupying form of attempt, which remain largely overlooked in these populations, especially regarding basic risk factors such as gender, addictive comorbidity and substance use patterns. Thus, we undertook a gender-specific approach to identify the risk factors for serious SAs in outpatients with multiple SUDs. Material and methods 433 Treatment-seeking outpatients were consecutively recruited in specialized care centers and reliably classified as serious, non-serious and non-suicide attempters. We also characterized lifetime exposure to SUDs, including tobacco smoking, with standardized instruments. Current medication, including psychotropic treatments were collected, which informed psychiatric diagnoses. Multinomial regression identified independent factors specifically associated with serious SAs in each gender, separately. Results 32% Participants (N = 139, 47% Women and 27% Men) reported lifetime SA. There were 82 serious attempters (59% of attempters), without significant gender difference. Sedative dependence was an independent risk factor for serious SA compared to non-SA in Women and compared to non-serious SA in Men, respectively. Other risk factors included later onset of daily tobacco smoking in Men and history of psychiatric hospitalizations in Women, whose serious SA risk was conversely lower when reporting opiate use disorder or mood disorder, probably because of treatment issues. Conclusions Despite several study limitations, we identified subgroups for a better-tailored prevention of serious SAs among individuals with SUDs, notably highlighting the need to better prevent and treat sedative dependence.

Importance: Community-based studies have linked psychotic experiences (PEs) with increased risks of suicidal thoughts and behaviors (STBs). However, it is not known if these associations vary across the life course or if mental disorders contribute to these associations.Objective: To examine the temporal association between PEs and subsequent STBs across the life span as well as the influence of mental disorders (antecedent to the STBs) on these associations.Design, Setting, and Participants: A total of 33 370 adult respondents across 19 countries from the World Health Organization World Mental Health Surveys were assessed for PEs, STBs (ie, ideation, plans, and attempts), and 21 DSM-IV mental disorders. Discrete-time survival analysis was used to investigate the associations of PEs with subsequent onset of STBs.Main Outcomes and Measures: Prevalence and frequency of STBs with PEs, and odds ratios and 95% CIs.Results: Of 33 370 included participants, among those with PEs (n = 2488), the lifetime prevalence (SE) of suicidal ideation, plans, and attempts was 28.5% (1.3), 10.8% (0.7), and 10.2% (0.7), respectively. Respondents with 1 or more PEs had 2-fold increased odds of subsequent STBs after adjusting for antecedent or intervening mental disorders (suicidal ideation: odds ratio, 2.2; 95% CI, 1.8-2.6; suicide plans: odds ratio, 2.1; 95% CI, 1.7-2.6; and suicide attempts: odds ratio, 1.9; 95% CI, 1.5-2.5). There were significant dose-response relationships of number of PE types with subsequent STBs that persisted after adjustment for mental disorders. Although PEs were significant predictors of subsequent STB onset across all life stages, associations were strongest in individuals 12 years and younger. After adjustment for antecedent mental disorders, the overall population attributable risk proportions for lifetime suicidal ideation, plans, and attempts associated with temporally prior PEs were 5.3%, 5.7%, and 4.8%, respectively.Conclusions and Relevance: Psychotic experiences are associated with elevated odds of subsequent STBs across the life course that cannot be explained by antecedent mental disorders. These results highlight the importance of including information about PEs in screening instruments designed to predict STBs.

The study aimed to examine the age of onset of stages of alcohol use in the general population, and to estimate the association of cohort use with the probability of transitioning from alcohol use to alcohol use disorder (AUD) and remission. French data (N = 2,894) from the European Study of the Epidemiology of Mental Disorders Survey and collected in 2000 were used. Data on lifetime history of alcohol use and DSM-IV alcohol use disorders, and remission were collected. Nearly every adult has consumed alcohol at least once in their lifetime (92.8%), and among users, 88.3% developed regular use, 6.0% met criteria for abuse and 1.7% for dependence. One-third of the population (32.8%) had used alcohol by the age of 15. Over 85% of cases of regular use were established prior to age 25, as were 61.1% of abuse and 39.4% of dependence cases. The proportion of people in an individual's age and sex cohort who had already used alcohol by a given age was positively and significantly associated with increased odds of transitioning to each stage examined. The findings highlight sensitive periods of life where persons are at greater risk for transitioning to a higher level of alcohol use, and underscore the importance of cohort use in transition risk.

Background: The prevalence of neuropsychiatric symptoms and substance abuse disorders, in adult patients with pulmonary Langerhans cell histiocytosis (PLCH) has not been explored. Objectives: The aim of this study was to examine the psychological healthcare burden faced by PLCH patients. Methods: All PLCH patients seen during one year completed the Hospital Anxiety and Depression scale (HAD), the Barratt Impulsiveness Scale, Version 10 (BIS-10) and the Cannabis Use Disorders Identification Test (CUDIT) questionnaires. Scores were used to determine the prevalence of psychological and substance abuse problems, and were associated with clinical assessment of the disease. The primary endpoint of the study was the proportion of patients having definite or doubtful anxious state (HAD-A scores of 11 or higher or between 8 and 10, respectively). Logistic regression models were used to quantify the strength of association of various disease-related parameters and the occurrence of anxiety, depression or impulsivity. Results: Sixty-eight patients were included. Definite anxious and depressive states were identified in 29% and 6% patients, respectively, and doubtful anxious and depressive states in 34% and 6%, respectively. Impulsive behaviour was detected in 13% of the cohort. Eleven patients (16%) consumed cannabis on a regular basis, and in 55% of them CUDIT scores suggested cannabis abuse or dependence. Increasing time from diagnosis and successful cessation of cigarette smoke exposure were associated with decreased risk of anxiety. Conclusions: Psychological abnormalities commonly co-exist in adult PLCH patients and should be considered while making their management decisions.

ObjectivesReligiosity is often associated with better health outcomes. The aim of the study was to examine associations between psychotic experiences (PEs) and religiosity in a large, cross-national sample.MethodsA total of 25 542 adult respondents across 18 countries from the WHO World Mental Health Surveys were assessed for PEs, religious affiliation and indices of religiosity, DSM-IV mental disorders and general medical conditions. Logistic regression models were used to estimate the association between PEs and religiosity with various adjustments.ResultsOf 25 542 included respondents, 85.6% (SE = 0.3) (n = 21 860) respondents reported having a religious affiliation. Overall, there was no association between religious affiliation status and PEs. Within the subgroup having a religious affiliation, four of five indices of religiosity were significantly associated with increased odds of PEs (odds ratios ranged from 1.3 to 1.9). The findings persisted after adjustments for mental disorders and/or general medical conditions, as well as religious denomination type. There was a significant association between increased religiosity and reporting more types of PEs.ConclusionsAmong individuals with religious affiliations, those who reported more religiosity on four of five indices had increased odds of PEs. Focussed and more qualitative research will be required to unravel the interrelationship between religiosity and PEs.

BackgroundResearch on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.MethodsThe WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.Results20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).ConclusionsWe found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.

Background The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians. Objective To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could be a useful way to boost the diagnosis of cocaine dependence. Methods A cross-sectional study of 221 cocaine users from several outpatient addiction treatment services in France, addressing the most severe period of cocaine use. DSM-IV cocaine dependence was determined with the MINI International Neuropsychiatric Interview (MINI). Physical symptoms before using cocaine were retrospectively assessed with a single item rated on a 0–5 scale. Results The prevalence of DSM-IV cocaine dependence was 84.6%. The mean score on the physical symptoms item was 1.3 (SD 1.3). A cut-off score of ≥ 1 on this item alone resulted in a sensitivity of 62%, a specificity of 88.2%, a positive predictive value of 96.6% and a negative predictive value of 29.7% to detect DSM IV cocaine dependence in this sample. Adding this item to a model with the frequency of cocaine use significantly increased the predictive power: Nagelkerke's R2 increased from .149 to .326 (p

Background and Objectives The burden of opiate dependence not only relies on somatic complications such as infectious diseases or acute intoxication but also on frequent psychiatric events such as major depressive disorder (MDD) and suicidal behavior (SB). Given the preclinical and clinical evidence regarding the associations between cannabinoid systems and both opiate dependence and psychiatric disorders, we chose to address whether one single nucleotide polymorphism (SNP) of the cannabinoid receptor type 1 gene (CNR1) named rs2023239 would be associated with lifetime MDD and SB in a population of opiate-dependent outpatients remitted under stable methadone treatment. Methods Sociodemographic and clinical data were included as independent factors in two logistic regression models aimed at predicting SB and MDD, respectively, performed with 85 Caucasian individuals. Results The minor C allele of rs2023239 showed an independent protective effect against lifetime MDD after adjustment for potential confounders. It was not associated with variables related to suicidal behavior. Conclusions and Scientific Significance Despite limitations due to the modest sample size, our results are consistent with previous research on the endocannabinoid system and suggest new leads for detecting subjects at risk of MDD, which remains insufficiently diagnosed and treated in patients suffering from severe addictive disorders. (Am J Addict 2015;XX:1 –8)

A personal history of childhood trauma has been associated with the severity of psychotic symptoms in several disorders. We evaluated retrospectively cocaine-induced psychotic symptoms with the SAPS-CIP and childhood trauma with the CTQ in a clinical sample of 144 cocaine users. The SAPS-CIP score was not statistically associated with the presence or number or intensity of trauma, but was associated with rapid routes of administration (intravenous and smoked) and with frequent cocaine use.

This study examined the prevalence of traumatic events and the conditional probability of posttraumatic stress disorder (PTSD) associated with both specific and broad classes of events in a nationally representative sample from France. The sample (N = 1,436) was a part of the European Study of the Epidemiology of Mental Disorders Survey (ESEMeD), under the WHO World Mental Health Surveys-2000 initiative. Overall, exposure to any traumatic event was 72.7%, which appeared to be lower than what has been reported in Sweden (80.8%), similar to data from the Netherlands (71.1%), and higher than what has been reported in Spain (54.0%), Italy (56.1%), Northern Ireland (60.6%) or the U.S (55.9%). Lifetime prevalence of PTSD was 3.9%, lower than in the United States (7.8%), Sweden (5.6%), or Northern Ireland (8.8%), but higher than in Spain (2.2%) or Italy (2.4%). Being beaten up by a romantic partner (25.0%), having a child with serious illness (23.5%), and rape (21.5%) were associated with the highest risk of PTSD. The average duration of PTSD was 5.3 years (0.2-28.1). The burden of PTSD in France appeared to come from the consequences of violence and social network events suggesting that prevention efforts might focus on limiting the occurrence of exposure to avoidable events such as violence as well as provide support for persons exposed to social network events. Language: en

Aims Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients.

Aims.A substantial proportion of persons with mental disorders seek treatment from complementary and alternative medicine (CAM) professionals. However, data on how CAM contacts vary across countries, mental disorders and their severity, and health care settings is largely lacking. The aim was therefore to investigate the prevalence of contacts with CAM providers in a large cross-national sample of persons with 12-month mental disorders.Methods.In the World Mental Health Surveys, the Composite International Diagnostic Interview was administered to determine the presence of past 12 month mental disorders in 138 801 participants aged 18–100 derived from representative general population samples. Participants were recruited between 2001 and 2012. Rates of self-reported CAM contacts for each of the 28 surveys across 25 countries and 12 mental disorder groups were calculated for all persons with past 12-month mental disorders. Mental disorders were grouped into mood disorders, anxiety disorders or behavioural disorders, and further divided by severity levels. Satisfaction with conventional care was also compared with CAM contact satisfaction.Results.An estimated 3.6% (standard error 0.2%) of persons with a past 12-month mental disorder reported a CAM contact, which was two times higher in high-income countries (4.6%; standard error 0.3%) than in low- and middle-income countries (2.3%; standard error 0.2%). CAM contacts were largely comparable for different disorder types, but particularly high in persons receiving conventional care (8.6–17.8%). CAM contacts increased with increasing mental disorder severity. Among persons receiving specialist mental health care, CAM contacts were reported by 14.0% for severe mood disorders, 16.2% for severe anxiety disorders and 22.5% for severe behavioural disorders. Satisfaction with care was comparable with respect to CAM contacts (78.3%) and conventional care (75.6%) in persons that received both.Conclusions.CAM contacts are common in persons with severe mental disorders, in high-income countries, and in persons receiving conventional care. Our findings support the notion of CAM as largely complementary but are in contrast to suggestions that this concerns person with only mild, transient complaints. There was no indication that persons were less satisfied by CAM visits than by receiving conventional care. We encourage health care professionals in conventional settings to openly discuss the care patients are receiving, whether conventional or not, and their reasons for doing so.

Current treatments of opioid addiction include primarily maintenance medications such as methadone. Chronic exposure to opiate and/or long-lasting maintenance treatment induce modulations of gene expression in brain and peripheral tissues. There is increasing evidence that epigenetic modifications underlie these modulations. This review summarizes published results on opioid-induced epigenetic changes in animal models and in patients. The epigenetic modifications observed with other drugs of abuse often used by opiate abusers are also outlined. Specific methadone maintenance treatment induced epigenetic modifications at different treatment stages may be combined with the ones resulting from patients’ substance use history. Therefore, research comparing groups of addicts with similar history and substances use disorders but contrasting for well-characterized treatment phenotypes should be encouraged.

BACKGROUND: Although specific phobia is highly prevalent, associated with impairment, and an important risk factor for the development of other mental disorders, cross-national epidemiological data are scarce, especially from low- and middle-income countries. This paper presents epidemiological data from 22 low-, lower-middle-, upper-middle- and high-income countries. METHOD: Data came from 25 representative population-based surveys conducted in 22 countries (2001-2011) as part of the World Health Organization World Mental Health Surveys initiative (n = 124 902). The presence of specific phobia as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition was evaluated using the World Health Organization Composite International Diagnostic Interview. RESULTS: The cross-national lifetime and 12-month prevalence rates of specific phobia were, respectively, 7.4% and 5.5%, being higher in females (9.8 and 7.7%) than in males (4.9% and 3.3%) and higher in high- and higher-middle-income countries than in low-/lower-middle-income countries. The median age of onset was young (8 years). Of the 12-month patients, 18.7% reported severe role impairment (13.3-21.9% across income groups) and 23.1% reported any treatment (9.6-30.1% across income groups). Lifetime co-morbidity was observed in 60.5% of those with lifetime specific phobia, with the onset of specific phobia preceding the other disorder in most cases (72.6%). Interestingly, rates of impairment, treatment use and co-morbidity increased with the number of fear subtypes. CONCLUSIONS: Specific phobia is common and associated with impairment in a considerable percentage of cases. Importantly, specific phobia often precedes the onset of other mental disorders, making it a possible early-life indicator of psychopathology vulnerability. This work was funded by the WHO WMH Survey Initiative, supported by the National Institute of Mental Health (NIMH; R01 MH070884), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864 and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481). 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 European Study of the Epidemiology of Mental Disorders (ESEMeD) project is 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 Ministry of Health and Ministry of Planning 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 WMH Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labour and Welfare. The Lebanese National Mental Health Survey (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) . 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). C.B. has received funding from the (Mexican) National Council of Science and Technology (grant CB-2010-01-155221). The South Africa Stress and Health Study (SASH) is supported by the US NIMH (R01-MH059575). The Psychiatric Enquiry to General Population in Southeast Spain – Murcia (PEGASUS-Murcia) Project has been financed by the Regional Health Authorities of Murcia (Servicio Murciano de Salud and Consejería de Sanidad y Política Social) and Fundación para la Formación e Investigación Sanitarias (FFIS) of Murcia. The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US NIMH (RO1-MH61905). The US National Comorbidity Survey Replication (NCS-R) is supported by the NIMH (U01-MH60220) with supplemental support from the NIDA, the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; grant 044708) . Preparation of this report was supported by a VICI grant (no: 91812607) received by P.d.J. from the Netherlands Research Foundation (NWO-ZonMW)

An association between serotonin 2A receptor (5-HT2AR), encoded by HTR2A gene, and major depressive disorder (MDD) has been suggested. Here, we combined preclinical and ecological clinical approaches to explore the impact of impaired 5-HT2AR-mediated transmission on MDD or anxio-depressive-like phenotype in mice. Htr2a knock-out mice (Htr2a(-/-)) and wild-type mice were compared for the ability of chronic corticosterone to elicit some anxio-depressive-like phenotype in three behavioral paradigms (elevated plus maze, tail suspension test and splash test). Accordingly, two single nucleotide polymorphisms of the HTR2A gene (rs6314 ie His452Tyr and rs6313 ie 102C/T), which specific allelic variants may decrease 5-HT2AR-mediated transmission (as in Htr2a(-/-)mice), were studied in a sample of 485 Caucasian patients with MDD. In response to chronic corticosterone exposure, Htr2a(-/-) mice displayed more pronounced anxiodepressive-like phenotype than wild-type mice, as shown by a significant higher "emotionality score" (p0.01). In patients, the C allele of rs6313 was more frequent in depressed patients (p=0.019) and was also associated with a more severe major depressive episode (p=0.03). This translational and ecological study involving constitutive Htr2a(-/-) knock-out mice and related SNPs in depressed patients suggests that a lower neurotransmission at the 5-HT2AR may favor the susceptibility and severity of MDE. It also suggests that specific allelic variants of the rs6313 and rs6314 may reduce 5-HT2AR-mediated transmission.

Resume Le fardeau lie aux problemes de sante, troubles mentaux inclus, a ete peu etudie en France. Aussi avons-nous analyse les donnees francaises resultant de l’enquete sur la sante mentale dans le monde (World Mental Health [WMH]) mise en place par l’Organisation mondiale de la sante (OMS), en nous interessant aux journees d’activite perdues liees a des problemes de sante courants en population generale. Des entretiens en face-a-face ont ete realises chez 2894 sujets (taux de reponse 45,9 %) afin de reperer dix maladies physiques et neuf troubles mentaux et d’evaluer les jours ou les sujets interroges n’avaient pas pu assurer leurs activites habituelles. L’association entre le nombre de jours d’inactivite et des troubles specifiques, comorbidites comprises, a ete evaluee par regression multiple. Mille quatre cent trente-six sujets ont ete inclus dans l’analyse. Le nombre de jours d’inactivite lies a des problemes de sante etait le plus eleve chez les sujets souffrant de troubles mentaux, tant au niveau individuel que societal. Les donnees de l’etude de sante mentale de l’OMS confirment l’importance des troubles mentaux dans les couts societaux en France et devrait permettre d’affiner les futures politiques de sante publique.

Background Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels’ genes could explain some of the “idiosyncratic” QT prolongations observed in patients treated with methadone, we tested the association between KCNE1 , KCNE2 , and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve. Methods A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1 , KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed. Results The mean QTc interval was 415 ± 34 ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2 , the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4 ms longer QTc (95% CI [4.6–26.2]; p = 0.001). Conclusion KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment.

Major Depressive Disorder (MDD) is the 3rd source for burden worldwide according to the World Health Organization (WHO). This comes partly from unsatisfactory response rates after usual treatment, highlighting the need for early indicators such as early improvement of depressive symptoms to adapt treatment strategies, especially for severe inpatients. Thus our objective was to assess the predictive value of baseline partial resistance in early antidepressant response (EAR), hypothesizing that previous treatment failures would decrease the probability of early response.We included 122 consecutive inpatients with current unipolar MDE. The Mini-Neuropsychiatric Interview was used to ascertain DSM-IV diagnoses of MDD as well as psychiatric comorbidities, and to exclude patients with a history of bipolar disorder. A specifically designed questionnaire was used to collect data on previous treatment trials for the current episode so as to generate scores on the five existing methods for quantifying treatment resistance. We prospectively assessed EAR, defined as a 50% decrease in MADRS after 14 days of steady regimen of antidepressant.In the per protocol sample (N=76), multivariate analyses showed that psychotic features at baseline remained an independent predictor of absence of EAR (p.01), unlike baseline partial resistance, which may rather be associated with a lack of any improvement.Lack of data about further response and non-randomized treatment allocation.Available methods for quantifying treatment resistance are heterogeneous and do not predict short-term response among severely depressed inpatients, despite potential usefulness in predicting a lack of early improvement.

BACKGROUND: Previous single country research has raised concerns that: (1) the DSM-IV diagnosis of alcohol abuse (AA) is met primarily through the hazardous use criterion related to drinking and driving and (2) that the hazardous use and social consequences AA criteria primarily reflect varying socioeconomic and cultural factors rather than psychiatric disorder. METHODS: Using representative cross-national data from the 21 countries in the World Mental Health surveys, adults meeting DSM-IV lifetime criteria for AA but not dependence from 10 developed (n = 46,071) and 11 developing (n = 49,761) countries were assessed as meeting AA with the hazardous use or the social consequences criteria. RESULTS: Between 29.3% (developed) and 16.2% (developing) of respondents with AA met only the hazardous use criterion. AA cases with and without hazardous use were similar in age-of-onset, course, predictors, and psychopathological consequences in both developed and developing countries. DISCUSSION AND CONCLUSIONS: Despite some associations of the AA criteria with socioeconomic factors, the hazardous use and social consequences criteria were significantly associated with psychiatric predictors and sequelae. The findings indicate that these criteria reflect psychiatric disorder and are appropriate for inclusion as DSM-5 Alcohol Use Disorder criteria. SCIENTIFIC SIGNIFICANCE: These findings support a psychiatric rather than a sociocultural view of the hazardous use and social consequences symptoms and provide evidence that they are appropriate diagnostic criteria cross-nationally with utility in a wide range of socioeconomic environments. This suggests consideration for their adoption by ICD-11. Further research is needed on the implications of these results for prevention and treatment. (Am J Addict 2014;23:145-155). Language: en

Summary Background Methadone is prescribed in France as a maintenance treatment for heroin dependence since 1969. Nevertheless, the optimal duration of methadone maintenance treatment and how detoxification from methadone at the end of the treatment should be performed is still discussed. Objective To conduct a literature review on when and how detoxify clients from methadone maintenance treatment and to collect the opinion of experts in the field. Documentary sources We searched the PubMed, Embase, Cochrane Library and PsycINFO databases on the 1966–2011 period using the keywords “methadone”, “maintenance”, “detoxification”, “tapering”, “cessation”, “withdrawal”. We also searched data in other addictive journals in French that are not available in those databases. We also collected the opinion of the physician in charge of the oldest methadone program in France (1969). Studies selection We excluded studies that used methadone as short time treatment of heroin withdrawal and thus selected 23 articles. Results There is a consensus on when methadone maintenance treatment should be stopped, defined by the client's will to stop , the judgement from the physician that the client has been stable for a period of time that is long enough , but also the client's motivation to live his life without maintenance treatment . There is also a majority, among articles on how methadone treatment should be stopped, recommending ambulatory, practical approaches using slow tapering of the dose , with the ability to go back to the previous dose if needed, namely in case of relapse to heroin use, heavy withdrawal or psychiatric symptoms. Limits There are few articles addressing the subject, especially comparing prospectively different cessation strategies. Conclusion Methadone maintenance treatment should not necessarily be maintained all life long and can be stopped within its prescription setting, including medical, psychological and social evaluation.

Aim: Methadone maintenance treatment is characterized by large interindividual dose variability. The aim of this study was to evaluate whether DNA methylations are associated with daily dose of methadone. Materials & methods: Subjects stabilized at high (n = 12) or low (n = 12) methadone doses were selected from two independent cohorts (French and Swiss). DNA methylation patterns were analyzed using HumanMethylation450 BeadChips. Results: In total, 584 differentially methylated sites were identified in the French cohort corresponding to 352 genes. Of these, 26 were replicated in the Swiss cohort. The methylation status of 13 genes varied similarly in both cohorts and calcium signaling pathway was significantly enriched. Conclusion: Our results indicate that differentially methylated sites are associated with methadone daily dose and give insights into the molecular pathways underlying this interindividual dose variability.

Bipolar disorder is a chronic, disabling, frequent and highly comorbid illness. It is often associated with addictive disorders (ADDs), another chronic and relapsing condition, with a lifetime prevalence three to five times higher than in the general population. However, knowledge is scarce about the possible mechanisms and the optimal treatment of this co-occurrence. Moreover, previous research has focused on separate ADDs, and few incidence data were available at the time. Our objective was, therefore, to evaluate the relevance of regrouping ADDs as classified in the preliminary version of the DSM-V in understanding the comorbidity of bipolar and ADDs.

Resume Introduction et objectif Les conduites suicidaires sont un reel probleme de sante publique en France. L’objectif de cette etude est d’evaluer la prevalence et les facteurs de risque associes aux comportements suicidaires (projet et tentative) a partir des donnees de l’etude ESEMeD. Methode Cette etude a ete menee en population generale adulte dans le cadre de l’etude ESEMeD qui est une composante de la World Mental Health (WMH) Survey conduite sous l’egide de l’OMS. Un total de 6796 foyers a ete selectionne et contacte. Les sujets etaient evalues a l’aide du Composite International Diagnostic Interview dans la version WMH Survey Initiative de l’OMS (WMH-CIDI) permettant le diagnostic des troubles selon les criteres du DSM IV et du CIM 10. Resultats Dans cette population, la prevalence sur la vie de l’ideation suicidaire, des projets et tentatives de suicide etait elevee, respectivement de 12,4 %, 4,4 % et 3,4 %. Concernant les facteurs de risque, la frequence de l’ideation et des conduites suicidaires en France est associee a l’âge (18–34 ans), au sexe feminin, a la presence d’un trouble psychiatrique et a la comorbidite psychiatrique. L’existence d’un projet suicidaire apparait comme etant un facteur predictif important d’un passage a l’acte suicidaire. Conclusion Les prevalences vie-entiere d’ideation suicidaire, de projets et de tentatives de suicide en population generale en France sont parmi les plus elevees par rapport aux autres pays. Dans un objectif plus large de prevention des comportements suicidaires, ces facteurs de risques doivent etre pris en consideration dans les politiques de sante publique.

This study aimed to develop a scale (Obsessive-Compulsive Cocaine Scale [OCCS]) for measuring cocaine craving based on the Obsessive Compulsive Drinking Scale (OCDS). We tested the scale on 116 French-speaking cocaine users. The scale was reliable (Cronbach's α= 0.93). It was significantly correlated with a visual analogue scale of craving (r = 0.641, p textless .001) and discriminated between cocaine-dependant subjects (score 36 ± 11) and abusers (score 17 ± 9, p textless .001). Prospective tests on a sample of 20 subjects showed that the OCCS score changed over 3 weeks of treatment and was significantly correlated with the visual analogue scale of craving (r = 0.492, p = .038). Principal component analysis identified three factors: resistance, intensity, and interference. The OCCS questionnaire could be used to repeatedly assess cocaine craving in prospective studies in cocaine addicts. (Am J Addict 2012;00:1-7).

Background Behavioural variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease that is clinically characterised by progressive behavioural changes and social interpersonal dysfunctions. Its diagnosis remains a clinical challenge, and depression is one of the main causes of misdiagnoses due to the prevalence of apathy in bvFTD. Objective To evaluate the sensitivity and specificity of the Social Cognition and Emotional Assessment (SEA) and the mini-SEA for differentiating bvFTD from major depressive disorder (MDD). Methods Scores for the SEA and mini-SEA for 37 patients with bvFTD (divided into subgroups of 17 with early bvFTD and 20 with moderate bvFTD according to the normal range of the Mattis Dementia Rating Scale), 19 MDD patients and 30 control subjects were compared to define the discrimination power of these tools compared with other standard neuropsychological tests. Results SEA and mini-SEA scores were significantly lower for both the early and moderate bvFTD groups compared with control subjects and the MDD group, and very few scores overlapped between patients in the bvFTD subgroups and patients in the MDD and control subgroups. SEA and mini-SEA scores distinguished early bvFTD from MDD with sensitivity and specificity rates above 94%. Conclusion Unlike standard executive neuropsychological tests, SEA and the mini-SEA can differentiate MDD from bvFTD in the early stages of the disease. The mini-SEA is an easy tool that can be utilised in neurological or psychiatric departments.

This study evaluates the French version of the Cannabis Use Disorders Identification Test (CUDIT) in a clinical sample with a high rate of cannabis misuse. A group of 194 cannabis users, including 134 outpatients (Group 1) seen at a specific cannabis clinic and 60 drug/alcohol addicts hospitalized for withdrawal (Group 2), filled out the CUDIT. The majority (82% of the sample) were cannabis dependent or abusers (DSM-IV). Internal reliability was assessed by Cronbach's alpha, item-total correlation by Spearman's rho and temporal reliability by the test-retest method. Construct validity was evaluated by factor analysis. Convergent validity was evaluated by measuring the correlation with the quantity of cannabis consumed. The cut-off score used to distinguish cannabis users from misusers was set using a Receiver Operating Characteristic curve analysis. Cronbach's alpha was high (0.83). There was no significant difference between the total test and retest scores (p = 0.1) indicating good temporal reliability....

The aim of this study was to evaluate the psychometric properties of the French version of the Marijuana Effect Expectancy Questionnaire (48 items) and study the cannabis expectancies according to the patterns of substance use and psychiatric disorders (DSM-IV). A sample of 263 subjects (average age 33.1 years [SD = 8.7], 56% men) consisting of cannabis users (n = 64), psychiatric inpatients (n = 175, most of whom were hospitalized for withdrawal), and a control group (n = 24) completed the questionnaire. Internal reliability was good (α= .87) and temporal reliability was satisfactory, with 24 of 48 items having a significant κ ≥ .41. Factor analysis showed four main factors that explained 42.1% of the total variance. The women feared Cognitive Impairment and Negative Effects, and Negative Behavioral Effects more than the men. The onset age of cannabis use, onset age of abuse, abuse and dependence were associated with fewer negative expectancies. Cannabis dependents differed from abusers by more Relaxation and Social Facilitation expectancies. Patients with major depressive episodes, panic disorder, social anxiety disorder, or posttraumatic stress disorder feared negative effects the most. Schizophrenic patients expected more Perceptual Enhancement and Craving. The French version of the Marijuana Effect Expectancy Questionnaire has good psychometric properties and is valid to assess cannabis expectancies in adolescents and adults with substance use disorders.

summary Cocaine addiction is a chronic disease marked by relapses, co-morbidities and the importance of psychosocial consequences. The etiology of cocaine addiction is complex and involves three types of factors: environmental factors, factors linked to the specific effects of cocaine and genetic factors. The latter could explain 40–60% of the risk for developing an addiction. Several studies have looked for a link between cocaine addiction and the genes of the dopaminergic system: the genes DRD2, COMT, SLC6A3 (coding for the dopamine transporter DAT) and DBH (coding for the dopamine beta hydroxylase) but unfortunately very few well established results. Pharmacogenetic approach could be an interesting opportunity for the future. The gene DBH has particularly been linked with the psychotic effects caused by cocaine. This so-called cocaine-induced psychosis (CIP) or cocaine-induced paranoia may influence the development of cocaine addiction. Indeed, these psychotic symptoms during cocaine exposure could cause an aversive effect limiting the development of an addiction. Several functional alterations caused by different mutations of the genes involved in dopaminergic transmission (principally-1021C > T of the gene DBH, but also Val158Met of the gene COMT, TaqI A of the gene DRD2 and VNTR 9 repeat of the DAT) could result in a cocaineinduced psychosis prone phenotype. We are hypothesising that the appearance of CIP during the first contact with cocaine is associated with a lower risk of developing cocaine addiction. This protective effect could be associated with the presence of one or more polymorphisms associated with CIP. A pharmacogenetic approach studying combination of polymorphism could isolate a sub-group of patients at risk for CIPs but more favorably protected from developing an addiction. This theory could enable a better understanding of the protective factors against cocaine addiction and offer new therapeutic or preventive targets in vulnerable sub-groups exposed to cocaine.

Morbidly obese patients are at significantly elevated risk of postsurgery complications and merit closer monitoring by health care professionals after bariatric surgery. It is now recognized that genetic factors influence individual patient’s response to drug used in anesthesia and analgesia. Among the many drug administered by anesthetists, we focused in this pilot study on morphine, since morphine patient-controlled anesthesia in obese patients undergoing gastric bypass surgery is frequently prescribed. We examined the allelic frequency of three polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in patients with body mass index (BMI) >40. One hundred and nine morbidly obese patients (BMI = 49.1 ± 7.7 kg/m²) were genotyped for three polymorphisms c.A118G of mu opioid receptor (OPRM1), c.C3435T of the P-glycoprotein gene (ABCB1), and p.Val158Met of catechol-O-methyltransferase gene (COMT). Allelic frequencies were 118G—0.22, C3435—0.55, and 158Met—0.5 in our whole population and 0.23, 0.5, and 0.47 in Caucasian population. Allelic frequencies did not differ according to gender. Mean BMI did no differ according to the allelic variant. OPRM1118G allele was more frequent in our population than in most previously described European populations. Since the concept of “personalized medicine” promises to individualize therapeutics and optimize medical treatment in term of efficacy and safety, especially when prescribing drugs with a narrow therapeutic index such as morphine, further clinical studies examining the clinical consequences of the OPRM1 c.A118G polymorphism in patients undergoing gastric bypass surgery are needed.

Staff members of psychiatric facilities are at high risk of secondhand smoking. Smoking exposure was assessed in 41 nonsmoking employees of a psychiatry department before and after a ban. Subjective exposure measures decreased in 76% of the subjects. Salivary cotinine decreased in the subsample of seven subjects with high pre-ban levels (32 ±8 vs 40 ± 17 ng/ml, p = .045).

Resume Les addictions avec substances representent un important probleme de sante publique. S’interesser a la frequence de la dependance et de l’abus aux differentes substances addictives permet de suivre l’evolution des consommations problematiques et de mettre en place des politiques de soins adaptees. Nous presenterons les etudes donnant des evaluations de la prevalence des consommations de tabac, d’alcool et de drogues illicites pour la France, l’Europe et plus largement au plan international. Celles-ci montrent une diminution de la consommation de tabac et de cannabis, tandis que la consommation d’alcool est en augmentation chez les jeunes adultes. Par ailleurs, on observe une uniformisation des modes de consommation suivant le sexe, particulierement chez les jeunes : les filles rejoignant les garcons. En revanche, il existe peu d’etudes d’epidemiologie analytique en population francaise permettant de decrire des facteurs de risque ou de protection. De meme, des etudes portant sur le parcours des usagers de substances psycho-actives en France, de l’usage a l’abus, puis a la dependance, ainsi que sur les strategies de sortie de la dependance (avec ou sans aide medicale) meriteraient d’etre conduites.

Resume Objectif et mesures Nous presentons les caracteristiques sociodemographiques, la prevalence de l’abus et de la dependance au cannabis et aux autres substances psychoactives (criteres DSM-IV) ainsi que la comorbidite des troubles mentaux dans les 12 derniers mois (diagnostics evalues par le Mini-International Neuropsychiatric Interview [MINI] et les criteres DSM-IV) chez 90 usagers de cannabis vus en consultation specialisee cannabis a l’hopital Lariboisiere. Resultats Les caracteristiques sociodemographiques des usagers associent : une predominance d’hommes (67 %), un âge moyen de 27,5 ans (±8,4), une majorite de celibataires ou divorces (59 %). Deux tiers des usagers (67 %) sont actifs ou etudiants et 32 % sont inactifs. D’un point de vue des ressources, 22 % des usagers percoivent l’allocation chomage, le RMI ou une AAH et 11 % sont sans aucune ressource. La majorite des usagers sont venus d’eux-memes (63 %) et la plupart ont deja consulte un psychologue ou un psychiatre par le passe (73 %). Les usagers sont pour la grande majorite dependants (82 %) et abuseurs (9 %) du cannabis dans les 12 derniers mois. En dehors du tabac, on retrouve une dependance a l’alcool chez seulement 7 % des usagers, une dependance a la cocaine ou a l’ecstasy chez 2 %. Les principales substances consommees sur la vie sont le tabac (99 %), l’alcool (96 %) et la cocaine (41 %). La consommation cannabique dans les six derniers mois est de 5,8 (±4,4) joints quotidiens, 12 (±10,5) g hebdomadaires et le cout mensuel de 159 € (±133). Le cannabis est consomme dans plus des trois quarts des cas sous forme de haschisch. Environ un usager sur deux (48 %) presente au moins un trouble de l’humeur et plus de la moitie (55 %) au moins un trouble anxieux dans les 12 derniers mois. Les troubles de l’humeur sont l’episode depressif majeur (38 %), la dysthymie (19 %), l’hypomanie (3 %) et la manie (1 %). Les troubles anxieux sont la phobie sociale (29 %), l’anxiete generalisee (17 %), le trouble panique avec et sans agoraphobie (16 %), le trouble obsessionnel compulsif (12 %), l’agoraphobie sans trouble panique (9 %) et le syndrome de stress post-traumatique (5 %). Le pourcentage de schizophrenes est de 4 %. Les femmes souffrent plus frequemment que les hommes d’au moins un trouble de l’humeur (64 % versus 41 % ; p = 0,04) ou d’un syndrome de stress post-traumatique (17 % versus 0 % ; p Conclusion En dehors du tabac, 80 % des usagers vus a notre consultation sont uniquement dependants ou abuseurs du cannabis. Les taux de dependance au cannabis sont tres eleves. En comparaison avec les etudes publiees sur les autres consultations specialisees cannabis en France, les usagers vus a l’hopital Lariboisiere sont plus âges, plus frequemment des femmes, plus dependants du cannabis et ont une comorbidite elevee de troubles de l’humeur et anxieux. Certains resultats de notre etude ont ete presentes lors de la reunion de l’Association francaise de psychiatrie biologique du 14 novembre 2006 [L’Encephale 33 (2007) 101].

BACKGROUND Studies describing long-term continuous care of outpatients with schizophrenia are relatively scarce. The prospective European Schizophrenia Outpatient Health Outcomes study (SOHO) provides data on a cohort of schizophrenic patients over a period of three years. METHODS Prospective, long-term, observational study including outpatients who initiate therapy or change to a new antipsychotic. The study was designed to provide two patient groups of approximately equal size: treated either with olanzapine or a non-olanzapine antipsychotic. Sociodemographic, clinical and disease characteristics at baseline were described. Clinical severity of symptoms was assessed at each visit using the Clinical Global Impression scale (CGI). Treatment outcomes were analyzed as treatment discontinuation, remission and relapse rates. RESULTS French results are presented in this report. Nine hundred and thirty-three patients (62% males) were recruited between March and December 2001. The mean age was 37.1+/-11.5 years. The mean time since first consultation for schizophrenia was 8.0+/-9.3 years. At study baseline, one quarter had paid employment, less than one third had a spouse or partner and more than half of them had an independent housing. Thirty percent of patients reported a previous suicide attempt. The mean CGI was 4.5+/-1.0 at admission. Overall, medication discontinuation for any cause occurred for 42% of patients. A remission (defined by a CGI

Cocaine is more and more used and abused in France. Cocaine dependence is quite serious and is associated with numerous adverse health consequences. No effective pharmacotherapy for cocaine dependence is yet available. Recent advances in neurobiology, brain imaging and some clinical trials suggest that certain medications that modulate GABAergic, dopaminergic, and glutamatergic systems, as well as immunotherapy, show promise in the treatment of cocaine addiction. Recent controlled clinical studies have tested some of these drugs, which act on the various neurobiological circuits modified by cocaine exposure and clinically improve patients' symptoms. Pharmacological agents such as modafinil, GABAergic agents (baclofen, topiramate, tiagabin, and vigabatrin), disulfiram, aripiprazole, N-acetylcysteine and cocaine vaccine seem very promising in the treatment of cocaine dependence. However, this must be confirmed in larger patient populations.

In this report, which is an update of a guideline published in 2002 (Bandelow et al. 2002, World J Biol Psychiatry 3:171), recommendations for the pharmacological treatment of anxiety disorder, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) are presented. Since the publication of the first version of this guideline, a substantial number of new randomized controlled studies of anxiolytics have been published. In particular, more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs. The recommendations, developed by the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-traumatic Stress Disorders, a consensus panel of 30 international experts, are now based on 510 published randomized, placebo- or comparator-controlled clinical studies (RCTs) and 130 open studies and case reports. First-line treatments for these disorders are selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors (SNRIs) and the calcium channel modulator pregabalin. Tricyclic antidepressants (TCAs) are equally effective for some disorders, but many are less well tolerated than the SSRIs/SNRIs. In treatment-resistant cases, benzodiazepines may be used when the patient does not have a history of substance abuse disorders. Potential treatment options for patients unresponsive to standard treatments are described in this overview. Although these guidelines focus on medications, non-pharmacological were also considered. Cognitive behavioural therapy (CBT) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders, OCD, and PTSD to support them being recommended either alone or in combination with the above medicines.

ResumenEsta investigación naturalista prospectiva examinó el papel del temor a la evaluación negativa y el rasgo de personalidad de evitación del daño en los niveles de ansiedad de pacientes con fobia social tratada. Se evaluó a 157 pacientes con fobia social del DSM-IV antes de comenzar el tratamiento y se los mantuvo en seguimiento durante un periodo de hasta dos años. Como se esperaba, el mayor temor a una evaluación negativa y las puntuaciones más altas de evitación del daño se asociaban con mayor ansiedad en el seguimiento a los 6 meses y la evitación del daño fue un predictor significativo a los 24 meses. Sin embargo, no se encontraron datos para una interacción entre la personalidad y las variables cognitivas examinadas. Los hallazgos se analizan desde el punto de vista de la independencia relativa de estos factores, así como sus implicaciones potenciales para el tratamiento de este trastorno.

ResumenObjetivoSe analizό las relaciones entre el psicotropo (PSP), el estado clínicos, la calidad de vida (CdV), el cumplimiento del tratamiento y el tipo de antipsicόtico para ver si la satisfaccion del paciente (SP) con el PSP se podía utilizar como variable de evoluciόn orientada al paciente en la evaluaciόn de los medicamentos PSP en los estudios epidemiolόgicos clinicos. Se evaluaron también elementos de validaciόn de los PSP.MetodoEn un estudio prospectivo de 6 meses, se seleccionó a 933 pacientes ambulatorios esquizofrénicos que iniciaron un tratamiento antipsicόtico o lo cambiaron. Los psiquiatras cumplimentaron un cuestionario con las cinco escalas de la CGI-SCH (positiva, negativa, cognitiva, depresiva y global) e informacion sobre la hospitalizaciόn, el cumplimiento y variables de la prescripciόn. Los pacientes respondieron a un cuestionario con informaciόn de PSP, escalas de EuroCdV, la funciόn sexual y variables de cumplimiento.ResultadosSe obtuvo un modelo de ecuaciones estructurales satisfactorio que mostraba relaciones significativas de PSP/cumplimiento (coef. = 0,16), CdV/PSP (coef. = 0,37), estado clinico/CdV (coef. = 0,61), estado cliníco/cumplimiento (coef. = 0,09). Los pacientes que recibieron olanzapina estaban más satisfechos que los que recibieron otros antipsicόticos atípicos (coef. = 0,12) y tenían un estado clínico mejor que los pacientes tratados con antipsicόticos típicos (coef. = 0,08). La evoluciόn del PSP se relacionaba con el estado clínico, la CdV y la continuaciόn del tratamiento (todas las P < 0,001). La sensibilidad al cambio del PSP era moderada (tamano del efecto = 0,2).ConclusiόnLos PSP produjeron resultados uniformes en relaciόn con los criterios de valoraciόn validados. Sin embargo, una medida de un elemento individual no era lo suficientemente sensible al cambio. Se necesitan cuestionarios multi-elemento que evalύen dimensiones diferentes.

This naturalistic, prospective investigation examined the role of fear of negative evaluation and the personality trait of harm avoidance in the anxiety levels of treated social phobia patients. One hundred and fifty-seven patients with DSM-IV social phobia were assessed before starting treatment and were then followed for up to two years. As expected, greater fear of negative evaluation and higher scores of harm avoidance were associated with greater anxiety at the 6 month follow-up, and harm avoidance remained a significant predictor at 24 months. However, no evidence was found for an interaction between the personality and cognitive variables examined. The findings are discussed in terms of the relative independence of these factors, as well as their potential implications for the treatment of this disorder.

Symptomatic remission is an achievable goal of treatment in patients with schizophrenia.The aim of this study was to determine the frequency of symptomatic remission and baseline factors associated with symptomatic remission in previously untreated patients with schizophrenia during 2 years of antipsychotic treatment.The Schizophrenia Health Outcomes (SOHO) study is a 3-year, prospective, observational study of the treatment of schizophrenia in the outpatient setting in ten European countries. Symptomatic remission was defined as a score ofor =3 on the clinical global impression (CGI) overall severity score, CGI positive symptoms score, CGI negative symptoms score and CGI cognitive symptoms score, maintained for at least 6 months and without hospitalisation.Of the patients enrolled at baseline, 1,009 patients were never-treated and prescribed only one antipsychotic; 701 patients (69%) were included in the follow-up analysis at 24 months. Of this sample, 70% achieved symptomatic remission during 24 months of treatment. Baseline factors associated with higher symptomatic remission were: lower negative CGI, lower cognitive CGI, lower overall CGI, having hostile behaviour, lower body mass index, taking olanzapine instead of typical antipsychotics or atypical antipsychotics (except risperidone) and being employed.A high proportion of patients with schizophrenia who start antipsychotic treatment achieve remission after 2 years of treatment. Type of medication, symptom severity and previous functioning are important predictors of outcome.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

The presence of cocaine dependence is under-recognized by cocaine users and requires a careful standardized interview to be ascertained by clinicians.To test if past experiences of cue-induced physical symptoms of craving (nausea, vomiting, sweating, shaking, nervousness) before cocaine use could be a useful way to boost the diagnosis of cocaine dependence.A cross-sectional study of 221 cocaine users from several outpatient addiction treatment services in France, addressing the most severe period of cocaine use. DSM-IV cocaine dependence was determined with the MINI International Neuropsychiatric Interview (MINI). Physical symptoms before using cocaine were retrospectively assessed with a single item rated on a 0-5 scale.The prevalence of DSM-IV cocaine dependence was 84.6%. The mean score on the physical symptoms item was 1.3 (SD 1.3). A cut-off score of ≥ 1 on this item alone resulted in a sensitivity of 62%, a specificity of 88.2%, a positive predictive value of 96.6% and a negative predictive value of 29.7% to detect DSM IV cocaine dependence in this sample. Adding this item to a model with the frequency of cocaine use significantly increased the predictive power: Nagelkerke's R(2) increased from .149 to .326 (p .001).Recalling past experiences of cue-induced physical signs of cocaine craving is associated with a clinical diagnosis of lifetime cocaine dependence and could be a simple way to improve its detection in clinical settings.