Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.

BACKGROUND: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).

BACKGROUND: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

Validation of a four items version of the Functional Remission of General Schizophrenia scale (the mini-FROGS) to capture the functional benefits of clinical remission.

OBJECTIVES: We previously developed the Functional Remission Of General Schizophrenia (FROGS) scale demonstrating first, reliable assessment in a cross-sectional study and second, good time-stability. The purpose of the present analysis was to propose a shorter version (mini-FROGS), more compatible with the limited time available in a psychiatric visit, focusing on the functional domains that have higher likelihood of being improved with higher and/or longer symptomatic remission in different cultural backgrounds. METHODS: We used multiple regressions to find the most informative items explaining increased length of symptomatic remission, using prospective data from a national observational multicenter survey. Then, the mini-FROGS was used in different European countries to test its between-center reliability, compared to other scales. RESULTS: Four domains were retained as capturing the maximum of symptomatic remission, namely (1) travel and communication, (2) management of illness and treatment, (3) self-esteem and sense of independence and (4) respect of biological rhythms. First, the mini-FROG was evaluated in 443 French patients with clinical remission and 22 without, and 12/18 months later in 140 patients still in clinical remission and 23 in relapse. In Europe, 295 schizophrenia patients were assessed with the mini-FROGS and other scales devoted to functional remission, allowing comparisons. The mini-FROGS showed good correlations with other scales in different countries and demonstrated good psychometric properties. CONCLUSION: These results give evidence that a 4 items-only version of the FROGS scale may be useful to assess important aspects of functional remission, tightly linked to the length of clinical remission.

[French Society for Biological Psychiatry and Neuropsychopharmacology and Fondation FondaMental task force: Formal Consensus for the management of treatment-resistant depression]. / Prise en charge des troubles dépressifs résistants : recommandations françaises formalisées par des experts de l'AFPBN et de la fondation FondaMental.

Major depression represents among the most frequent psychiatric disorders in the general population with an estimated lifetime prevalence of 16-17%. It is characterized by high levels of comorbidities with other psychiatric conditions or somatic diseases as well as a recurrent or chronic course in 50 to 80% of the cases leading to negative repercussions on the daily functioning, with an impaired quality of life, and to severe direct/indirect costs. Large cohort studies have supported that failure of a first-line antidepressant treatment is observed in more than 60% of patients. In this case, several treatment strategies have been proposed by classical evidence-based guidelines from internationally recognized scientific societies, referring primarily on: I) the switch to another antidepressant of the same or different class; II) the combination with another antidepressant of complementary pharmacological profile; III) the addition of a wide range of pharmacological agents intending to potentiate the therapeutic effects of the ongoing antidepressant medication; IV) the association with appropriate psychological therapies; and, V) the use of non-invasive brain stimulation techniques. However, although based on the most recently available data and rigorous methodology, standard guidelines have the significant disadvantage of not covering a large variety of clinical conditions, while currently observed in everyday clinical practice. From these considerations, formalized recommendations by a large panel of French experts in the management of depressed patients have been developed under the shared sponsorship of the French Association of Biological Psychiatry and Neuropsychopharmacology (AFPBN) and the Fondation FondaMental. These French recommendations are presented in this special issue in order to provide relevant information about the treatment choices to make, depending particularly on the clinical response to previous treatment lines or the complexity of clinical situations (clinical features, specific populations, psychiatric comorbidities, etc.). Thus, the present approach will be especially helpful for the clinicians enabling to substantially facilitate and guide their clinical decision when confronted to difficult-to-treat forms of major depression in the daily clinical practice. This will be expected to significantly improve the poor prognosis of the treatment-resistant depression thereby lowering the clinical, functional and costly impact owing directly to the disease.

Hypovitaminosis D and Its Associated Factors in North Algerian Postmenopausal Women: Results of a Cross-Sectional Study.

PURPOSE: As the vitamin D status of Algerian postmenopausal women was poorly described, this cross-sectional study investigated the prevalence of low vitamin D status in a sample population. Secondarily, predictive factors of this hypovitaminosis D were explored. METHODS: All the 336 selected women ≥ 45 years from Douera were interviewed to get anthropometric and lifestyle data, reproductive and medical history, medications, and calcium/vitamin D intakes. A blood sample was collected to measure 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS: Approximately 86% of subjects had low vitamin D status (<20 ng/mL). Mean 25(OH)D level was 14.4 ± 5.3 ng/mL with a clear seasonal dynamic and a significant negative correlation with PTH levels (r = -0.15, p=0.006). A multiple regression analysis using the 25(OH)D cutoff value of 17 ng/mL instead of the generally admitted level of 20 ng/mL was performed to increase statistical power. Other seasons than summer (OR 4.159 and 95% CI 2.456-7.043), obesity (≥30 kg/m2, OR 1.826, 95% CI 1.081-3.083), and veiling (OR 3.526, 95% CI 1.090-11.400) were significantly associated with 25(OH)D concentrations <17 ng/mL. CONCLUSIONS: In North Algeria, the abundant sunlight appears insufficient to fully offset hypovitaminosis D risk factors in postmenopausal women, especially obesity and veiling. It suggests the major need to increase vitamin D supplementation in this subpopulation.

[French Society for Biological Psychiatry and Neuropsychopharmacology task force. Formal consensus for the treatment of bipolar disorder: an update (2014)]. / Recommandations Formalisées d'Experts de l'Association Française de Psychiatrie Biologique et Neuropsychopharmacologie sur le dépistage et prise en charge du trouble bipolaire : mise à jour 2014.

As part of a process to improve the quality of care, the French Society for Biological Psychiatry and Neuropsychopharmacology developed in 2010 formal consensus guidelines for the treatment of bipolar disorder. The evolution of therapeutic options available in France for the treatment of bipolar disorder has justified the update of this guideline. The purpose of this work was to provide an updated and ergonomic document to promote its use by clinicians. This update focuses on two of the six thematic previously published (acute treatment and long-term treatment). Aspects of the treatment of bipolar patients sparking debate and questions of clinicians (use of antidepressant, place of the bitherapy, interest of long-acting antipsychotics…) were also covered. Finally, we proposed graded recommendations taking into account specifically the risk-benefit balance of each molecule.

[French Society for Biological Psychiatry and Neuropsychopharmacology task force: Formal Consensus for the prescription of depot antipsychotics]. / Recommandations Formalisées d'Experts de l'AFPBN : prescription des neuroleptiques et antipsychotiques d'action prolongée.

BACKGROUND: Compliance is often partial with oral antipsychotics and underestimated for patients with serious mental illness. Despite their demonstrated advantages in terms of relapse prevention, depot formulations are still poorly used in routine. As part of a process to improve the quality of care, French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) Task Force elaborated a Formal Consensus for the prescription of depot antipsychotics in clinical practice. METHODS: The Task Force recommends as first-line choice, the use of long-acting injectable (LAI) second-generation antipsychotics in patients with schizophrenia, schizoaffective disorder and delusional disorder. They can be considered as a second-line option as a monotherapy to prevent manic recurrence or in combination with mood stabilizer to prevent depressive recurrence in the maintenance treatment of bipolar disorder. LAI second-generation antipsychotics can also be used after a first episode of schizophrenia. Depot neuroleptics are not recommended during the early course of schizophrenia and are not appropriate in bipolar disorder. They are considered as a second-line option for maintenance treatment in schizophrenia. RESULTS: LAI formulations should be systematically proposed to any patients for whom maintenance antipsychotic treatment is indicated. LAI antipsychotics can be used preferentially for non-compliant patients with frequent relapses or aggressive behaviors. CONCLUSION: A specific information concerning the advantages and inconveniences of the LAI formulations, in the framework of shared-decision making must be delivered to each patient. Recommendations for switching from one oral/LAI form to another LAI and for using LAI antipsychotics in specific populations (pregnant women, elderly patients, subjects in a precarious situation, and subjects having to be treated in a prison establishment) are also proposed.

[Evaluation of functional remission in schizophrenic disorder. The FROGS Scale]. / Évaluation de la rémission fonctionnelle dans le trouble schizophrénique: l'échelle FROGS.

INTRODUCTION: Functional remission is an important treatment goal in schizophrenia, as independent living and reintegration of patients into the community is the ultimate goal of any treatment. Nevertheless, assessing functional remission in schizophrenia is problematic, as it is a multifactorial entity reflecting various aspects such as symptoms severity, personal skills and sociocultural expectancies. METHOD: The purpose of this study was to create and validate a novel scale for the evaluation of functional remission in schizophrenia. Unlike previous scales, this one was built on the basis of patients with few schizophrenia symptoms. The "Functional Remission of General Schizophrenia" (FROGS) scale was developed using the expert consensus method following a MEDLINE and standard database search. Out of the 61 initially proposed, 19 items were selected as gathering the core aspects of functional remission in schizophrenia detected in the literature. The FROGS was then evaluated in 432 patients with DSM-IV criteria of schizophrenia, all of them meeting Andreasen's symptomatic remission criteria. Such an instrument should have a stable structure over time but also be able to detect improvement in functioning with time. So we have further analysed the validity of the FROGS scale, specifically assessing time stability. We re-evaluated the initial patient sample around 1.5 years after the first evaluation (mean=17.1 months ± 1.9), restricting the analyses to patients who were still being followed-up and in clinical remission (n=140). RESULTS: Total score was highly reliable. Exploratory factor analysis after oblique rotation revealed that a three-factor solution was the most meaningful. On the basis of item content these three factors were labelled 'Social Functioning', 'Daily Life' and 'Treatment'. The FROGS total score can be used to measure a general construct for the evaluation of functional remission in schizophrenia. The mean FROGS total score was 75.8 (sd=10.8) at the second evaluation showing a significant improvement with time (3.8; P<0.0001 versus the first evaluation). The internal consistency/reliability of the FROGS scale was still very high (Cronbach's α=0.919). Significant improvement between the first and second evaluation were also apparent for all the individual items in the FROGS scale (P<0.01) as well as for the subscores for three extracted factors (P<0.0001). Statistically significant correlations were observed between the FROGS scale and other indices, including the Global Assessment of functioning (r=0.58; P<0.0001). These results provide further evidence of the solid psychometric properties of the FROGS scale. DISCUSSION/CONCLUSION: The results of these two validation studies provide further evidence of the scale's utility and its solid psychometric properties. Furthermore, it is sensitive to the duration of clinical remission. Our scale may be a step towards developing a consensual definition of functional remission in schizophrenia.

Religious involvement in major depression: protective or risky behavior? The relevance of bipolar spectrum.

BACKGROUND: Religiosity has been reported to be inversely related to depression and to suicide as well, but there is a lack of studies on its impact on bipolar disorder and especially, on depressed patients belonging to the bipolar spectrum. 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, 234 (55.2%) could be classified as with high religious involvement (HRI), and 190 (44.8%) as with low religious involvement (LRI), on the basis of their ratings on the Duke Religious Index (DRI). RESULTS: Compared to LRI, HRI patients did not differ with respect to their religious affiliation but had a later age at onset of their affective illness with more hospitalizations, suicide attempts, associated hypomanic features, switches under antidepressant treatment, prescription of tricyclics, comorbid obsessive compulsive disorder, and family history of affective disorder in first-degree relatives. The following independent variables were associated with religious involvement: age, depressive temperament, mixed polarity of first episode, and chronic depression. The clinical picture of depressive patients with HRI was evocative of chronic mixed depressive episodes described in bipolar III patients within the spectrum of bipolar disorders. LIMITATIONS: Retrospective design, recall bias, lack of sample homogeneity, no assessment of potential protective and risk factors, and not representative for all religious affiliations. CONCLUSIONS: In depressive patients belonging to the bipolar spectrum, high religious involvement associated with mixed features may increase the risk of suicidal behavior, despite the existence of religious affiliation.

Factors associated with borderline personality disorder in major depressive patients and their relationship to bipolarity.

OBJECTIVE: To analyze the interface between borderline personality disorder (BPD) and bipolarity in depressed patients comorbid with BPD. METHODS: As part of National Multi-site Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 19 (3.9%) had comorbid BPD (BPD+), whereas 474 (96.1%) did not manifest this comorbidity (BPD-). RESULTS: Compared to BPD (-), BPD (+) patients displayed higher rates of bipolar (BP) disorders and temperaments, an earlier age at onset with a family history of affective illness, more comorbidity, more stressors before the first episode which was more often depressive or mixed, as well as a greater number and severity of affective episodes. CONCLUSIONS: The hypothesis which fitted at best our findings was to consider BPD as a contributory factor in the development of BP disorder, which could have favoured the progression from unipolar major depression to BP disorder. We could not however exclude that some features of BP disorder may have contributed to the development of BPD.

[New medical device hospital assessment: what kind of clinical data?]. / Évaluation des DM innovants au sein des hôpitaux : avec quelles données cliniques ?

INTRODUCTION: Since 2003, the AP-HP medical devices committee (CODIMS) assess the therapeutic relevance of innovated medical device (MD) for the French AP-HP hospitals' group. To accomplish this task, the CODIMS asks manufacturers to bring out clinical arguments to justify the use of their MD in hospital. This work analyses retrospectively after 8years, all assessed MD until March 2011 and the scientific quality of the clinical data submitted by manufacturers to the CODIMS to purchase their MD. METHOD: All MD were classed according to their certification's level (I, IIa, IIb, III, DMIA). The quality of available clinical studies (CS) provided by manufacturers for each case was assessed and classed according to five clinical relevance levels based on the evidence-based medecine standards (1-2: high methodology; 3-5: low methodology). RESULTS: One hundred and three MD files (80 % of class IIb and III MD) were analysed by the CODIMS (630CS). Our results highlight the lack of relevance of files that are provided to assess innovated MD: 29 files without any CS; concerning class IIb (32DMS, 221CS) and III (50, 342CS) MD, only 6 % of CS presented a correct clinical relevance level. And the situation did not get better during this assessment period. DISCUSSION/CONCLUSION: The CODIMS deplore the poor clinical relevance of files provided to assess MD (wrong comparator, inappropriate ends-points, insufficient follow-up to assess long-term security, small population studied). Future legislative developments for MD assessment are expected to improve this situation.

Time-stability of the "Functional Remission of General Schizophrenia" (FROGS) scale.

Functional remission in schizophrenia is an important treatment goal, particularly for patients who have achieved symptomatic remission. The Functional Remission of General Schizophrenia (FROGS) scale has recently been developed, with the FROGS total score being reported as reliable in a cross-sectional study, with an exploratory factor analysis showing three oblique meaningful factors. As such an instrument should have a stable structure over time, but also be able to detect improvement of functioning with time, we have further analysed the validity of the FROGS scale, specifically assessing time-stability. We re-evaluated the initial patient sample around 1.5 years after the first evaluation (mean=17.1 months, standard deviation=1.9), restricting the analyses to patients who were still being followed-up and in clinical remission (n=140 patients). The mean (standard deviation) FROGS total score was 75.82 (10.85) at the second evaluation, showing a significant improvement with time (3.84; P<0.0001 versus the first evaluation). The internal consistency/reliability of the FROGS scale was still very high (Cronbach's α=0.919). Significant improvements between the first and second evaluations were also apparent for all the individual items in the FROGS scale (P<0.01) as well as for the subscores for the three extracted factors (P<0.0001). Statistically significant correlations were observed between the FROGS scale and other indices, including the Global Assessment of Functioning (r=0.58; P<0.0001). These results provide further evidence of the solid psychometric properties of the FROGS scale.

Baseline and prodromal characteristics of first- versus multiple-episode mania in a French cohort of bipolar patients.

OBJECTIVE: To identify some of the main features of bipolar disorder for both first-episode (FE) mania and the preceding prodromal phase, in order to increase earlier recognition. METHODS: One thousand and ninety manic patients (FE=81, multiple-episodes [ME]=1009) were assessed for clinical and temperamental characteristics. RESULTS: Compared to ME, FE patients reported more psychotic and less depressive symptoms but were comparable with respect to temperamental measures and comorbid anxiety. The following independent variables were associated with FE mania: a shorter delay before correct diagnosis, greater substance use, being not divorced, greater stressors before current mania, a prior diagnosis of an anxiety disorder, lower levels of depression during index manic episode, and more suicide attempts in the past year. CONCLUSION: In FE patients, the diagnosis of mania may be overlooked, as they present with more psychotic symptoms than ME patients. The prodromal phase is characterised by high levels of stress, suicide attempts, anxiety disorders and alcohol or substance abuse. Data suggest to consider these prodromes as harmful consequences of temperamental predispositions to bipolar disorder that may concur to precipitate mania onset. Their occurrence should therefore incite clinicians to screen for the presence of such predispositions, in order to identify patients at risk of FE mania.

"Folie circulaire" vs "Folie à double forme": contribution from a French national study.

OBJECTIVE: To check whether the presence or not of free intervals between episodes could help differentiate subtypes of bipolar disorder, as suggested by the seminal controversy between Falret and Baillarger. METHODS: From 1090 bipolar I patients included in a French national study, 981 could be classified as with or without free intervals and assessed for demographic and illness characteristics. RESULTS: Compared with patients with free intervals (n=722), those without (n=259) had an earlier age at onset, more episodes, suicide attempts, cyclothymic and irritable temperaments. The following independent variables were associated with no free intervals: being single or divorced, delay to mood stabilizer treatment, multiple hospitalizations, incongruent psychotic features, panic and generalized anxiety disorder. CONCLUSION: "Folie à double forme" (without free intervals) and "folie circulaire" (with free intervals) may actually refer to early and later onset bipolar subtypes, insofar as most differences we found between them were previously evidenced between the latter two. We cannot, however, exclude that they might simply be two separate subtypes, whose main characteristics could be accounted for by different explanatory factors.

[Ductal carcinoma in situ of the breast (DCIS). Histopathological features and treatment modalities: analysis of 1,289 cases]. / Carcinomes canalaires in situ (CCIS). Caractéristiques histopathologiques et traitement : analyse de 1 289 cas.

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Suicidal behaviour in a French Cohort of major depressive patients: characteristics of attempters and nonattempters.

BACKGROUND: Epidemiological and clinical studies indicate that major depressive disorder is the leading cause of suicidal behaviour and that bipolar II subjects carry the highest risk. Identification of risk factors is therefore essential to prevent suicide in this population. 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 1month apart, 155 (33.7%) were classified as suicide attempters, and 295 (66.3%) as nonattempters, after exclusion of bipolar I patients. RESULTS: Compared to nonattempters, attempters had a longer duration of illness, longer delays before seeking help and correct diagnosis and a higher number of previous episodes; they were more frequently rapid cyclers, with fewer free intervals between episodes. Lifetime suicide attempts were associated with more comorbid bulimia and substance abuse. Bipolar II spectrum disorders, depressive, cyclothymic and irritable temperaments were overrepresented in attempters, as well as family history of both affective disorder and suicide attempts. The following independent variables were associated with lifetime suicide attempts: higher number of previous depressive episodes, multiple hospitalizations, cyclothymic temperament, rapid cycling and earlier age at onset. LIMITATIONS: Retrospective design, recall bias, lack of sample homogeneity, and insufficient assessment of hypomanic features during index depression. CONCLUSIONS: In major depressive disorders, family history, age at onset, illness course, comorbidity and cyclothymic temperament alongside other indices of bipolarity may help predict suicidal behaviour. Longer delays to seeking help and diagnosis in attempters emphasize the importance of early recognition of bipolar spectrum disorders.

Breast-conserving surgery with or without radiotherapy vs mastectomy for ductal carcinoma in situ: French Survey experience.

From March 2003 to April 2004, 77 physicians throughout France prospectively recruited 1289 ductal carcinoma in situ (DCIS) patients and collected data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). Ductal carcinoma in situ was diagnosed by mammography in 87.6% of patients. Mastectomy, conservative surgery alone (CS) and CS with radiotherapy (CS+RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Thus, 89% of patients treated by CS received adjuvant RT. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients (80% tamoxifen). Median tumour size was 14.5 mm (6, 11 and 35 mm for CS, CS+RT and mastectomy, respectively, P<0.0001). Nuclear grade was high in 21% of patients, intermediate in 38.5% and low in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS+RT) of patients. Oestrogen receptors were positive in 69.8% of assessed cases (31%). Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin and grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

Is psychosis in DSM-IV mania due to severity? The relevance of selected demographic and comorbid social-phobic features.

OBJECTIVE: We tested whether factors other than episode severity contributed to psychosis in mania. METHOD: Psychiatrists collected systematic clinical data on 1090 hospitalized DSM-IV manic patients in France, and completed the Mania Rating Scale (MRS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: Using DSM-IV specifiers, 21.9% were non-severe, 28.2% severe without psychosis, and 49.9% severe with psychosis. On the MRS, patients with psychosis scored significantly higher (P < 0.0001) than non-severe, but did not differ from the severe without psychosis. We found significant correlations between both the Hallucination and the Delusion subscores of the SAPS and the MRS, as well as correlations between age, single marital status, comorbid social phobia and psychotic mania. CONCLUSION: Apart from episode severity, social isolation - associated with younger age, single marital status and social phobia - seems to make a contribution to the origin of manic psychosis largely independent from such severity.

The treatment of negative symptoms and deficit states of chronic schizophrenia: olanzapine compared to amisulpride and placebo in a 6-month double-blind controlled clinical trial.

OBJECTIVE: The aim of the study was to evaluate the efficacy of olanzapine (5 and 20 mg/day) over a 6-month period in chronic schizophrenic patients experiencing predominantly negative symptoms. METHOD: Two hundred and forty-four patients participated in a 6-month multicenter double-blind trial of placebo (n = 34), olanzapine 5 mg/day (n = 70), olanzapine 20 mg/day (n = 70), or amisulpride 150 mg/day (n = 70). Primary measure was the scale for the assessment of negative symptoms. RESULTS: Olanzapine 5 mg/day showed significantly greater improvement than placebo in negative symptoms and in the Positive and Negative Syndrome Scale total score. Baseline positive symptoms were low at baseline and changed minimally. The neurological tolerance of olanzapine, amisulpride and placebo were comparable. CONCLUSION: Olanzapine 5 mg/day was effective in treating negative symptoms in a group of schizophrenic with predominantly negative symptoms during the stabilization phase. Improvement in positive symptoms or extrapyramidal symptoms (EPS) was unlikely to explain this result while improvement in depression may have partially contributed.

Validating the soft bipolar spectrum in the French National EPIDEP Study: the prominence of BP-II 1/2.

BACKGROUND: Much of the current literature on bipolar disorder is focused on bipolar I (BP-I), and to a much lesser extent on bipolar II (BP-II). The French multi-center national EPIDEP study has, among its objectives, the feasibility of validating a broader spectrum of bipolarity (the so-called "soft spectrum") by practicing clinicians. In this report we test aspects of a bipolar schema proposed earlier by Akiskal and Pinto [Akiskal, H.S., Pinto, O., 1999. The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22: 517-534.]. METHODS: EPIDEP was scheduled in three phases: Phase 1 to recruit DSM-IV major depressives; Phase 2 to assess hypomania and affective temperaments; and Phase 3 to obtain history on course of illness, family history, and comorbidity. Comparative analyses are presented between affective subgroups constructed on a hierarchical basis: spontaneous hypomania (BP-II), cyclothymic temperament (BP-II 1/2), antidepressant-associated hypomania (BP-III), hyperthymic temperament (BP-IV), versus "strict unipolar" (UP). RESULTS: We present data on 490 patients for whom we obtained full assessment during all three phases of the study, classified as BP-II 1/2 (N=164), II (N=61), III (N=28), IV (N=22), as well as UP (N=174) as the reference nonbipolar group. Systematic inter-group comparison among the soft spectrum showed significant differences along clinical, descriptive, course, pharmacologic response and familial affective disorder patterns, which confirm the heterogeneity of the soft bipolar spectrum, with special characteristics for each of the subgroups. In terms of external validation, familial bipolar loading characterized all soft bipolar subgroups except type IV. LIMITATION: Data collection conducted in a practice setting, clinicians cannot be entirely held "blind" to all measures. This is an exploratory attempt, with many variables examined, to help characterize the clinical terrain of soft bipolarity. CONCLUSION: This is nonetheless the first systematic clinical attempt to validate the bipolar spectrum beyond mania (BP-I). BP-II 1/2, BP-III and BP-IV appeared distinct from BP-II and strict UP -- along most of the variables examined. BP-II 1/2 -- with early onset complex temperament structure, and high mood instability, rapid switching, irritable ("dark") hypomania and suicidality -- emerged as the most prevalent and severe expression of the bipolar spectrum, and accounting for 33% of all MDE. These results, which are of great public health relevance, testify to the cyclic nature of bipolarity in its softest expressions. The soft phenotypes are also of interest for genetic investigations of bipolar disorder.