Effectiveness of a Fully Automated Internet-Based Smoking Cessation Program: A Randomized Controlled Trial (STAMP).

Introduction: The Internet offers an interesting alternative to face-to-face and telephone-based support for smoking cessation. This study was designed to assess the effectiveness of a personalized and automated Internet-based program. Methods: French current adult smokers willing to quit within 2 weeks were recruited for a randomized controlled trial. The intervention consisted of an automated program of 45 e-mails ("e-coaching") sent over a 3-month period. The control group received a PDF version of a booklet on smoking cessation. Self-reported 7-day point prevalence smoking abstinence was measured at 6 months (primary outcome), at 3 and 12 months of follow-up (secondary outcomes). Results: 2478 smokers were randomized (1242 for e-coaching, 1236 for the booklet). Cessation rate in the intention-to-treat population was not significantly different between the two groups at 6 and 12 months, but was higher in the e-coaching group at 3 months than in the control group (27.5% vs. 23.5%, p = .02, odds ratio [OR] = 1.24, confidence interval [CI] = [1.03-1.49]). After adjustment for baseline conditions, the effect of the intervention in the per-protocol (PP) sample was significant at 3 months (adjusted odds ratio [aOR] = 1.72 [1.31-2.28], p < .001, N = 1042) and at 6 months (aOR = 1.27 [1.00-1.60], p = .05, N = 1082). GLM repeated measure analyses showed significant group by time interaction in the intent-to-treat and a significant group effect in the PP population. Conclusions: Analyzed intention-to-treat, e-coaching was superior to a booklet at 3 months (end of intervention) but no more superior at 6 and 12 months follow-up. Among those who actually followed the program, the effectiveness is also observed 3 months after the intervention is stopped. Implications: Analyzed intention-to-treat, our French tailored and personalized Internet-based cessation program was superior to a smoking cessation booklet at 3 months (end of intervention) but no more superior at 6 months follow-up. Among those who actually followed the program (PP population), the effectiveness is observed in the short-term but also 3 months after the intervention is stopped.

Guidelines for the use and management of long-acting injectable antipsychotics in serious mental illness.

BACKGROUND: Long-acting injectable (LAI) formulations are not widely used in routine practice even though they offer advantages in terms of relapse prevention. As part of a process to improve the quality of care, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) elaborated guidelines for the use and management of antipsychotic depots in clinical practice. METHODS: Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations concerning 3 fields: target-population, prescription and use, and specific populations. We contacted 53 national experts, 42 of whom (79%) completed the survey. The options were scored using a 9-point scale derived from the Rand Corporation and the University of California in the USA. According to the answers, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. The first-line option was defined as a strategy rated as 7-9 (extremely appropriate) by at least 50% of the experts. The following results summarize the key recommendations from the guidelines after data analysis and interpretation of the results of the survey by the scientific committee. RESULTS: LAI antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder, delusional disorder and bipolar disorder. LAI second-generation antipsychotics are recommended as maintenance treatment after the first episode of schizophrenia. LAI first-generation antipsychotics are not recommended in the early course of schizophrenia and are not usually appropriate in bipolar disorder. LAI antipsychotics have long been viewed as a treatment that should only be used for a small subgroup of patients with non-compliance, frequent relapses or who pose a risk to others. The panel considers that LAI antipsychotics should be considered and systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. Recommendations for medication management when switching oral antipsychotics to LAI antipsychotics are proposed. Recommendations are also given for the use of LAI in specific populations. CONCLUSION: In an evidence-based clinical approach, psychiatrists, through shared decision-making, should be systematically offering to most patients that require long-term antipsychotic treatment an LAI antipsychotic as a first-line treatment.

Methodological differences between pharmacological treatment guidelines for bipolar disorder: what to do for the clinicians?

OBJECTIVE: Numerous guidelines for bipolar disorder have been published. The aim of this article is to underline the main differences between consensus-based guidelines (CBG) and evidence-based guidelines (EBG) currently available for the management of bipolar disorder. METHODS: A literature search for guidelines published since 2006 was performed. A qualitative analysis was then conducted to compare the methodologies and the guidelines contents. RESULTS: Comparison between CBG and EBG found more similarities than differences. However, discordances were found in the first-line choice of treatment (monotherapy or combination, use of lamotrigine or lithium in bipolar depression), time to reassessment and duration of maintenance treatment, introduction as from the acute phase a regimen compatible with long-term use and pharmacotherapy during pregnancy. CONCLUSIONS: The choice of policy, whatever the methodology used, is up to the authors and can, therefore, depend on their interpretation of the available scientific evidence. Combining both methodologies (CBG and EBG) enables us to meet the complete definition of evidence-based medicine.

Health management of older persons with chronically medicated psychotic disorders: the results of a survey in France.

BACKGROUND: The medical care of elderly patients with psychotic disorders is a matter of major concern. The aim of the study was to investigate health conditions and treatment of elderly patients with psychotic disorders in France. METHODS: The SAGE (Schizophrenia AGEd) study (observational, cross-sectional) was a survey conducted among 123 physicians in France, regarding prescriptions of antipsychotic drugs in elderly patients (≥60 years) suffering from psychotic disorders. The survey was based on a questionnaire addressing the mental and somatic health management of the patients. RESULTS: Data from 930 patients (mean age: 70.4 years) were collected. Most patients (58.5%) suffered from schizophrenia, 20.8% had delusional disorder and 20.6% hallucinatory chronic psychosis (very-late-onset schizophrenia-like psychosis). 70.8% of them were outpatients, while 29.2% were inpatients. The severity of psychotic symptoms was assessed in 97.8% of patients, but cognitive function was only evaluated in 41.6%. Some 46.5% of patients were treated with atypical antipsychotics alone, 36.2% with classical antipsychotics alone and 17.3% received a combination of both, atypical and classical antipsychotics; 36.3% patients were given antiparkinsonian medication, of whom only 17.8% as preventive treatment; 51.1% of patients had somatic comorbidities, particularly cardiovascular disorders (34.0%). Evaluation of renal and/or liver function to adjust the dose of treatment was done in only 32.1% of patients. Over the previous 12 months, almost half of the patients had had no ECG, glycemia or creatininemia investigated and HDL-cholesterol and triglycerides were available for less than one-third of them. CONCLUSIONS: Antipsychotic and antiparkinsonian drug prescriptions in French aged psychotic patients follow only partially the clinical guidelines and recommendations of consensus conferences. Moreover, cognitive, cardiac and metabolic aspects are not fully managed as expected.

Impact of an educational program on the management of bipolar disorder in primary care.

OBJECTIVE: Government agencies and industry have recently undertaken educational programs for the management of bipolar disorder in primary care, but their medical impact is not well known. Therefore, we conducted a survey among general practitioners to evaluate the impact of the Bipolact Educational Program on the diagnosis and treatment of bipolar disorder. METHODS: A total of 45 general practitioners attending the Bipolact Educational Program (trained group) were compared with a control group of 50 untrained general practitioners on their ability to: (i) diagnose bipolar I and II disorders and (ii) treat bipolar disorder patients appropriately. RESULTS: Trained physicians, but not untrained physicians, showed a significant improvement (p < 0.0001, chi-square test) in the ability to identify patients as having bipolar I (from 10.4% to 28.8%) and bipolar II disorder (from 20.1% to 45.8%). This trend resulted in a strong decrease in nonidentified bipolar disorder patients (from 64.6% to 19.5%). Trained physicians, but not the untrained group, greatly increased the number of prescriptions for mood stabilizers for bipolar disorder patients, from 25.6% to 43.2% (p = 0.0013, chi-square test). Finally, trained physicians reduced the number of antidepressant prescriptions for bipolar disorder patients (the control group also reduced the number of antidepressant prescriptions, suggesting some bias in the survey). CONCLUSION: A well-designed education package on diagnosis and management of bipolar disorder greatly increased the likelihood of physicians correctly assigning a subtype, namely bipolar I or bipolar II disorder, to patients already perceived as having some form of bipolar illness, and to prescribing mood stabilizers instead of antidepressants to these patients.

Risk factors associated with lifetime suicide attempts in bipolar I patients: findings from a French National Cohort.

Risk factors that may be associated with suicide attempts in bipolar disorder are still a matter of debate. We compared demographic, illness course, clinical, and temperamental features of suicide attempters vs those of nonattempters in a large sample of bipolar I patients admitted for an index manic episode. One thousand ninety patients (attempters = 382, nonattempters = 708) were included in the study. Multivariate analysis evidenced 8 risk factors associated with lifetime suicide attempts as follows: multiple hospitalizations, depressive or mixed polarity of first episode, presence of stressful life events before illness onset, younger age at onset, no free intervals between episodes, female sex, higher number of previous episodes, and cyclothymic temperament. These characteristics may help identify subjects at risk for suicide attempt throughout the course of bipolar disorder. We finally propose to integrate such characteristics into a stress-diathesis model of suicidal behavior, adapted to bipolar patients.

Psychopathological correlates of lifetime anxiety comorbidity in bipolar I patients: findings from a French national cohort.

BACKGROUND: Despite numerous studies on the comorbidity of bipolar and anxiety disorders, there is no satisfactory psychopathological model for their overlap. METHOD: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode of bipolar I disorder were subtyped according to the presence or not of lifetime anxiety comorbidity and assessed for demographic, illness course, clinical, associated condition, temperament, and treatment characteristics. RESULTS: Lifetime anxiety comorbidity, defined as presence of at least one anxiety disorder in lifetime, was found in 27.2% (n = 297) of the sample. Compared to patients without such a comorbidity (n = 793), those who had it experienced a higher number of mood episodes and suicide attempts in the previous year, more stressors, organic disorders and less free intervals; furthermore, they showed more temperaments with depressive features and complex treatment. At study entry, they also experienced manic episodes with higher levels of depression, psychosis and hostility. The following independent variables were associated with lifetime anxiety comorbidity: higher scores on the Montgomery-Asberg Depression Rating Scale, depressive temperament, irritable temperament, higher scores on the Scale for the Assessment of Positive Symptoms, episodes without free intervals and at least one stressor before the index episode. CONCLUSIONS: Factors associated with lifetime anxiety comorbidity in bipolar I patients may be integrated into a comprehensive diathesis-stress model emphasizing the role of irritable temperament as a source of mood instability and stress, and interacting with other temperamental characteristics to trigger the outbreak of both anxiety and bipolar symptoms.

Predictive factors of functional remission in patients with early to mid-stage schizophrenia treated by long acting antipsychotics and the specific role of clinical remission.

BACKGROUND: Functional remission has become a major therapeutic objective in schizophrenia, but the probability of such positive outcome has a large variability, ranging from 15% to 51%. Additionally, how clinical remission constitutes a prerequisite for functional remission also remains unclear. METHODS: A prospective observational study was conducted in French schizophrenic patients who initiated treatment with a long-acting injectable (LAI) after an acute episode. Functional and clinical remissions were assessed using the FROGS and the Andreasen criteria, and the role of clinical remission and predictive factors of functional remission was evaluated. RESULTS: Three hundred three patients with schizophrenia (DSM-IV criteria) were followed for 12 months. At 12 months, 45.1% of the patients reached functional remission while 55.1% obtained clinical remission. Clinical remission facilitated functional remission (OR = 14.74), especially in patients with psychosis for less than 5 years (OR = 23.73). Other predictive factors concerned the family environment, education level, employment status, baseline functioning levels and level of insight. CONCLUSIONS: About half of patients treated with LAI reached functional remission after one year of follow-up. Reduced clinical symptoms and reaching clinical remission largely favored functional remission. These results stress the importance of continuous and appropriate symptomatic treatment to reach functional remission and maximize recovery chances.

Factors associated with rapid cycling in bipolar I manic patients: findings from a French national study.

INTRODUCTION: Despite numerous explanatory hypotheses, few studies have involved a large national clinical sample examining risk factors in the occurrence of rapid cycling during the course of bipolar illness. METHODS: From 1,090 manic bipolar I disorder inpatients included in a multicenter national study in France, 958 could be classified as rapid or nonrapid cyclers and assessed for demographic, illness course, clinical, psychometric, temperament, comorbidity, and treatment characteristics. RESULTS: Rapid cycling bipolar disorder occurred in 9% (n=86) of the study group. Compared to nonrapid cyclers (n=872), patients with rapid cycling experienced the onset of their illness at a younger age, a higher number of prior episodes, more depression during the first episode, and more suicide attempts. At study entry, they also experienced manic episodes with more depressive and anxious symptoms, but less psychotic features. The following independent variables were associated with rapid cycling: longer duration of illness, antidepressant treatment, episodes with no free intervals, cyclothymic temperament, lower scores on the Scale for Assessment of Positive Symptoms and presence of thyroid disorder. Retrospective study limited to bipolar I disorder inpatients; several factors previously associated with rapid cycling were not assessed. CONCLUSION: Our findings may confirm previous descriptions, according to which rapid cycling develops later in the course of illness following a sensitization process triggered by antidepressant use or thyroid dysfunction, in patients with a depression-mania-free interval course, and cyclothymic temperament.

Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort. Comparisons with prior cluster analytic investigations.

BACKGROUND: Knowledge about psychopathologic presentations of mania in current clinical practice has to be refined in order to improve diagnosis and treatment. METHODS: One thousand ninety manic patients included in the French National Study EPIMAN-II Mille were submitted to a cluster analysis on the basis of multiple variables related to the history of bipolar illness and symptoms of the current episode. RESULTS: Four clusters were identified: "classic mania" (29.3% of patients) with less severe mania; "psychotic mania" (22.7%) with psychotic symptoms, more severe mania, younger age and social impairment; "depressive mania" (30.4%) characterized by female gender, suicide attempts, high number of previous episodes and residual symptoms; and "dual mania" (17.6%) characterized by male gender, substance use, earlier onset and poor compliance. Patients groups also differed in manic symptoms, marital status, stressors preceding illness onset, prior diagnoses, first episode polarity and temperamental characteristics. LIMITATIONS: Cross-sectional assessment of patients. CONCLUSIONS: In comparing our findings with those of four prior cluster analytic studies, we integrate clinical characteristics of mania subtypes found in this very large representative French sample in contemporary practice, we suggest how such convergence of data may help improve earlier recognition, differential response to different treatments, and prevention of these subtypes. We finally suggest that such subtyping might provide clues to phenotype delineation suitable for pharmacogenetic investigations.

Functional remission in schizophrenia: A FROGS-based definition and its convergent validity.

Functional remission concerns only one third of schizophrenia patients who achieved symptomatic remission. We previously developed a scale devoted to functional remission, named the FROGS (Functional Remission Of General Schizophrenia). This instrument encompasses three clinically relevant dimensions. The aim of this study is to provide a threshold for functional remission relying on these three dimensions, and to compare its psychometric properties with other scales devoted to functional remission. We tested the characteristics of functional remission according to the FROGS. The FROGS was used in different European countries and compared to other valid scales (GAF, PSP and PSRS) in a sample of 295 schizophrenia patients. The association with different parameters as external validators was assessed, including clinical remission. A comparison of the classifying properties of each scale compared to the others was made. The four instruments were equally influenced by the PANSS score, the clinical remission according Andreassen's criteria, the number of past hospitalizations and the presence of a paid working activity. These findings provide a simple threshold for the FROGS, tightly linked to the definition of functional remission, with a good convergent validity. This instrument might be easily used to facilitate the assessment of functional remission in schizophrenia.

Validation of a severity threshold for the Mania Rating Scale: a receiver-operating characteristic analysis.

BACKGROUND: The aim of this study was to determine a cutoff score on the Mania Rating Scale (MRS), which easily allows identification of severe mania in a population of manic patients to be included in clinical trials of antimanic drugs. METHOD: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode were subtyped according to the specifier for severity and assessed for demographic characteristics, illness course and clinical symptomatology. Using receiver-operating characteristic (ROC) analysis, the optimal threshold for severity was determined on the MRS. RESULTS: In a French national clinical sample (n = 1,090), 851 cases were specified as severe and 239 as nonsevere (mild + moderate) mania according to DSM-IV criteria (307 without psychotic features, 544 with psychotic features). Patients with severe mania scored higher on the MRS but showed the same levels of scores on the Montgomery Asberg Depression Rating Scale compared to nonsevere cases. Many characteristics of the whole sample and of the psychotic group were found to be comparable, respectively, to those reported in recent epidemiological studies, which was particularly true for age, gender, age at onset, number of mood episodes and suicide attempts. The optimal ROC solution for separating severe from nonsevere mania was a cutoff score of 39 on the MRS. This cutoff score displayed a positive predictive value of 0.91. CONCLUSION: A cutoff score of 39 is proposed as a severity threshold for mania on the MRS by virtue of its ROC validation in a large representative sample of severe versus nonsevere manic patients whose severity was assessed according to DSM-IV subtyping.

GOSPEL 3: Management of gout by primary-care physicians and office-based rheumatologists in France in the early 21st century - comparison with 2006 EULAR Recommendations.

INTRODUCTION: In 2006, recommendations about the management of gout were issued by the European League Against Rheumatism (EULAR). The objective of this work was to compare these recommendations to practice patterns of physicians working in private practices in France. METHOD: In a prospective multicenter nationwide study conducted in France, a random sample of primary-care physicians (PCPs) and private-practice rheumatologists (PPRs) was taken in 2009. Each physician included 2 consecutive patients with gout. Each patient was evaluated twice at an interval of 3-6months. Information on EULAR 2006 management modalities were collected in a standardized manner. RESULTS: Of 1003 patients, 771 were evaluated twice. Allopurinol was prescribed to 75.1% of patients in all and was initiated at the first study visit in 44 patients, among whom 19 (43.2%) 19 patients received the recommended starting dosage of 100mg/day. Colchicine therapy to prevent flares was prescribed to 74.3% of patients. Of the 522 patients on allopurinol therapy at the first visit, only 34.5% had serum uric acid levels≤360µmoL/L (mean dosage, 173 mg/day). Excessive dietary intake by patients who were overweight or obese was recorded in 31.5% of patients seen by PCPs and in 19.7% of those seen by OBRs. This finding prompted the delivery of nutritional advice to 45.8% of patients. Discontinuation of excessive alcohol intake was recommended to only 10% of patients. Diuretic therapy discontinuation was feasible in 175 patients but was recommended in only 7 patients. CONCLUSION: Differences between practice patterns and 2006 EULAR recommendations were identified. Simplifying the recommendations and teaching them during medical training and continued medical education may deserve consideration.

Validating the bipolar spectrum in the French National EPIDEP Study: overview of the phenomenology and relative prevalence of its clinical prototypes.

BACKGROUND: Few studies have been undertaken to ascertain the feasibility of using the bipolar (BP) spectrum in clinical practice. The only systematic national study is the French EPIDEP Study of consecutive inpatients and outpatients presenting with major depressive episodes (MDE). The protocol was developed in 1994 and implemented in 1995; publication of its first data began in 1998. This report provides the complete data set of the EPIDEP. METHODS: Forty-eight psychiatrists, practicing in 15 sites in four regions of France (Paris, Besançon, Bordeaux and Marseille), were all trained on a common protocol based on DSM-IV criteria for MDE (n=537) subdivided into BP-I (history of mania), BP-II (history of hypomania), as well as extended definitions of the "softer spectrum" beyond BP-I and BP-II. Measures tapping into this spectrum included the Hypomania Checklist (HCA), the cyclothymic (CT), depressive (DT) and hyperthymic (HT) temperament scales. These measures and course permitted post-hoc assignment of MDE in the bipolar spectrum, based in part on the Akiskal, H.S., Pinto, O., 1999. [The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22, 517-534] proposal: depression with history of spontaneous hypomanic episodes (DSM-IV, BP-II), cyclothymic depressions (BP-II(1/2)), antidepressant-associated hypomania (BP-III) and hyperthymic depressions (BP-IV). <> was thereby limited to an exclusion diagnosis for the remainder of MDE. LIMITATION: In the clinical setting, psychiatrists cannot be entirely blind to the observations in the various clinical evaluations and instruments. However, the systematic multisite collection of such data tended to minimize any such biases. RESULTS: After excluding patients lost to follow-up, among 493 presenting with MDE with complete data files, the BP-II rate was estimated at index at 20%; 1 month later, systematic probing for hypomania doubled the rate of BP-II to 39%. The comparison between BP-II and UP showed differential phenomenology, such as hypersomnia, increased psychomotor activation, guilt feelings and suicidal thoughts in BP-II. Related data demonstrated the importance of CT in further qualifying of MDE to define a distinct, more severe ("darker") BP-II(1/2) variant of BP-II. Moreover, BP-III, arising from DT and associated with antidepressants, emerged as a valid soft bipolar variant on the basis of the phenomenology of hypomania and bipolar family history. Finally, we found preliminary evidence for the inclusion of BP-IV into the bipolar spectrum, its total hypomania score falling intermediate between BP-II and strict UP. Using this broader diagnostic framework, the bipolar spectrum (the combined "hard" BP-I phenotype, BP-II and the soft spectrum) accounted for 65% of MDE. CONCLUSION: The EPIDEP study achieved its objectives by demonstrating the feasibility of identifying the bipolar spectrum at a national level, and refining its phenomenology through rigorous clinical characterization and validation of bipolar spectrum subtypes, including MDE with brief hypomanias, cyclothymia and hyperthymia. The spectrum accounted for two out of three MDE, making "strict UP" less prevalent than BP as redefined herein. Our findings were anticipated by Falret, who in 1854 had predicted that many melancholic patients in the community would 1 day be classified in his circular group. We also confirmed Baillarger's observation in the same year that episodes (in this study, hypomanic episodes) could last as short as 2 days. Our findings deriving from a systematic French national database a century and a half later invite major shifts in clinical and public health services, as well as in the future conduct of psychopharmacologic trials. In this respect, the systematic training of clinicians in four regions of France represents a national resource for affective disorders and can serve as a model to effect change in diagnostic practice in other countries.

GOSPEL 2 - Colchicine for the treatment of gout flares in France - a GOSPEL survey subgroup analysis. Doses used in common practices regardless of renal impairment and age.

OBJECTIVES: The objective of this sub-study was to assess the use of colchicine for the treatment of gout flares in real life conditions in the GOSPEL cohort following the 2006 EULAR recommendations for gout management. METHODS: This national cross-sectional epidemiologic survey included outpatients with gout suffering from acute flare followed by randomly selected primary care physicians (n=398) and private practice rheumatologists (n=109) between October 2008 and September 2009 in France. Data regarding patient characteristics and treatment prescription was collected by each physician. Glomerular filtration rate (eGFR) was estimated using the Cockroft-Gault formula. Patients included in the survey for a gout flare filled in a specific self-questionnaire including colchicine effective intake and pain relief (numeric scale). RESULTS: This analysis focused on the 349 patients presenting with gout flare and treated with colchicine. Mean (±SD) prescribed dose of colchicine was 2.8 (±0.7) mg within the first 24hours and the cumulative dose over the first three days of treatment was 6.9 (±1.8) mg. Patients with mild decline in eGFR (eDFG 60-80mL/min) were prescribed an average initial dose of 2.8mg (±0.8) mg (n=58), 2.7 (±0.8) mg in chronic kidney disease (CKD) stage 3 (n=43) and 2.5 (±0.7) mg in CKD stage 4 (n=2). Cumulative doses of colchicine did not take into account either renal impairment or age. CONCLUSIONS: This study draws attention to some misuse of colchicine in daily practice and the prescription of excessive doses especially in case of renal impairment. eGFR should be enforced in daily practice.

Lazabemide, a selective, reversible monoamine oxidase B inhibitor, as an aid to smoking cessation.

BACKGROUND: Previous research has shown that smokers have reduced brain and platelet monoamine oxidase B (MAOB) activity. This is probably due to some components of tobacco smoke. When smokers quit, MAOB activity returns to normal. Reduced MAO activity may increase nicotine's addictive potential. AIMS: To assess whether lazabemide, a reversible selective MAOB inhibitor, promotes smoking cessation. STUDY DESIGN: Double-blind, randomized, placebo-controlled, multicenter phase II study. Placebo, lazabemide 100 mg/day and 200 mg/day were administered for 8 weeks. This was a dose finding, proof-of-concept, exploratory study. SETTING: General practices and anti-smoking clinics in France and Belgium. PARTICIPANTS: Smokers smoking > or=15 cigarettes per day and motivated to quit. MAIN OUTCOME MEASURE: Sustained abstinence during the last 4 weeks of the study. FINDINGS: The study was discontinued prematurely by the sponsor before randomization of the planned 420 smokers because of liver toxicity observed in other indications. Data of 330 randomized subjects could be analysed. Sustained abstinence during the last 4 weeks of treatment was 9%, 11% and 17% in the intent-to-treat population [P for trend: 0.036 (one-sided)]; 11%, 14% and 21% in the intent-to-treat population of smokers without those excluded because of discontinuation of the study [n = 262, P for trend: 0.02 (one-sided)], and 19%, 27% and 35% in completers [P for trend: 0.03 (one-sided)], in the placebo, lazabemide 100 mg/day and lazabemide 200 mg/day groups, respectively. Point prevalence abstinence (intent-to-treat population) at the end of treatment (week 8) was 17%, 19% and 30% in the placebo, lazabemide 100 mg/day and lazabemide 200 mg/day groups, respectively (placebo vs. lazabemide 200 mg/day: P = 0.01, one-sided). No treatment emergent major adverse event occurred. More nausea and insomnia were reported with lazabemide than with placebo. CONCLUSIONS: MAOB inhibitors are promising treatments as an aid in smoking cessation. There may be an interest to develop MAOB inhibitors with an acceptable toxicity profile. Further studies may associate MAOB inhibitors with nicotine replacement therapies to increase therapeutic efficacy.

The Modified Reasons for Smoking Scale: factorial structure, gender effects and relationship with nicotine dependence and smoking cessation in French smokers.

AIMS: To assess the validity of the French version of the Modified Reasons for Smoking Scale (MRSS), and to identify which smoking patterns differentiate male and female smokers, which are related to tobacco dependence (as assessed by the Fagerström Test for Nicotine Dependence, FTND), to mood (Beck Depression Inventory II), to affect (Positive and Negative Affect Schedule) and which are predictors of successful quitting. PARTICIPANTS: Three hundred and thirty smokers [(mean +/- SD) aged 40 +/- 9 years, 145 (44%) women, mean FTND score: 6.2 +/- 2], candidates for a smoking cessation programme and smoking at least 15 cigarettes/day. FINDINGS: Factor analysis of the 21-item scale gave the optimal fit for a seven-factor model, which accounted for 62.3% of the total variance. The following factors were identified: 'addictive smoking', 'pleasure from smoking', 'tension reduction/relaxation', 'social smoking', 'stimulation', 'habit/automatism' and 'handling'. The 'addictive smoking' score increased in a dose-dependent manner with number of cigarettes smoked per day; the 'habit/automatism' score was significantly higher, with more than 20 cigarettes per day than with < or = 20 cigarettes per day. The reasons for smoking were different for males and females: females scored higher on 'tension reduction/relaxation', 'stimulation' and 'social smoking'. A high level of dependence (FTND > or = 6) was associated with significantly higher scores only on 'addictive smoking', the association being stronger in females. Time to first cigarette after awakening was associated with higher 'addictive smoking' and 'habit/automatism' (P < 0.001). In a multivariate logistic regression, failed quitting was predicted by higher habit/automatism score (odds ratio = 1.44, 95% CI = 1.06-1.95, P = 0.02) and greater number of cigarettes smoked per day (odds ratio = 1.03, 95% CI = 1.01-1.06, p = 0.03). CONCLUSIONS: The questionnaire yielded a coherent factor structure; women smoked more for tension reduction/relaxation, stimulation and for social reasons than men; addictive smoking and automatic smoking behaviour were similar in both sexes and were associated strongly with a high level of nicotine dependence; the 'habit/automatism' score predicted failure to quit over and above cigarettes per day.

Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II).

BACKGROUND: According to DSM-IV and ICD-10, hypomania which occurs solely during antidepressant treatment does not belong to the category of bipolar II (BP-II). METHODS: As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 144 (29.2%) fulfilled the criteria for bipolar II with spontaneous hypomania (BP-II Sp), and 52 (10.5%) had hypomania associated solely with antidepressants (BP-H AA). RESULTS: BP-II Sp group had earlier age at onset, more hypomanic episodes, and higher ratings on cyclothymic and hyperthymic temperaments, and abused alcohol more often. The two groups were indistinguishable on the hypomania checklist score (12.2+/-4.0 vs. 11.4+/-4.4, respectively, P=0.25) and on rates of familial bipolarity (14.1% vs. 11.8%, respectively, P=0.68). But BP-H AA had significantly more family history of suicide, had higher ratings on depressive temperament, with greater chronicity of depression, were more likely to be admitted to the hospital for suicidal depressions, and were more likely to have psychotic features; finally, clinicians were more likely to treat them with ECT, lithium and mood stabilizing anticonvulsants. LIMITATION: Naturalistic study, where treatment was uncontrolled. CONCLUSION: BP-H AA emerges as a disorder with depressive temperamental instability, manifesting hypomania later in life (and, by definition, during pharmacotherapy only). By the standards of clinicians who have taken care of these patients for long periods of time, BP-H AA appears as no less bipolar than those with prototypical BP-II. We submit that familial bipolarity ('genotypic' bipolarity) strongly favors their inclusion within the realm of bipolar II spectrum, as a prognostically less favorable depression-prone phenotype of this disorder, and which is susceptible to destabilization under antidepressant treatment. These considerations argue for revisions of DSM-IV and ICD-10 conventions. BP-HAA may represent a genetically less penetrant expression of BP-II; phenotypically; it might provisionally be categorized as bipolar III.