DSM-5 mixed specifier for manic episodes: evaluating the effect of depressive features on severity and treatment outcome using asenapine clinical trial data.

BACKGROUND: To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome. METHODS: This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items. RESULTS: Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61-43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36-37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64-67%), whereas remission decreased with increasing severity with olanzapine (63-38%) and placebo (49-25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients. LIMITATIONS: Results are from post-hoc analyses. CONCLUSIONS: These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.

Effect of asenapine on manic and depressive symptoms in bipolar I patients with mixed episodes: results from post hoc analyses.

BACKGROUND: The efficacy of agents useful for mania is largely unproven in patients with mixed episodes. METHODS: The efficacy of asenapine in the treatment of mixed episodes was assessed using post hoc analyses on pooled data from two identically designed 3-week, randomized, double-blind, flexible dose, placebo- and olanzapine-controlled trials and their 9-week, double-blind olanzapine-controlled extension study. Efficacy was measured by changes on Young Mania Rating Scale (YMRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) total scores, and was analysed through analysis of covariance on observed cases of the intent-to-treat dataset. RESULTS: In the intent-to-treat population, 295 patients had a DSM-IV-TR mixed episode (placebo: 66; olanzapine: 122; asenapine: 107) in the 3-week trials. Of these, 102 patients (olanzapine: 56; asenapine: 46) entered the 9-week extension study. At week 3, decreases in YMRS and MADRS total scores, were significantly (p<0.01) greater with asenapine (YMRS: -15.0; MADRS: -8.2) versus placebo (YMRS: -11.5; MADRS: -4.5); olanzapine did not separate from placebo (YMRS: -13.3; MADRS: -6.5). At week 12, further decreases in YMRS and MADRS total scores were observed with asenapine (YMRS: -22.4; MADRS: -11.9); non-statistically different from olanzapine (YMRS: -20.2; MADRS: -7.9). LIMITATIONS: Results are from post hoc analyses of trials that were not designed to specifically evaluate mixed episodes. CONCLUSIONS: These exploratory analyses provide supportive evidence for the efficacy of asenapine in treating the associated symptoms of mania and depression in bipolar I patients with mixed episodes.

Baseline anxiety effect on outcome of SSRI treatment in patients with severe depression: escitalopram vs paroxetine.

OBJECTIVE: To investigate if treatment outcome for severely depressed patients depends on their baseline level of anxiety. RESEARCH DESIGN AND METHODS: Patients with a primary diagnosis of severe major depressive disorder (n = 459) were randomised to 24 weeks of double-blind treatment with escitalopram (20 mg) or paroxetine (40 mg). Post hoc analyses of efficacy in patients with a baseline HAM-A total score < or =20 (n = 171) or >20 (n = 280) were based on analysis of covariance (ANCOVA) (ITT, LOCF). RESULTS: At week 24, the mean change from baseline in MADRS total scores was -24.2 for escitalopram-treated patients (n = 141) and -21.5 for paroxetine-treated patients (n = 139) (p < 0.05) in high baseline anxiety patients and the mean change from baseline in HAM-A total score was -17.4 (escitalopram) and -15.1 (paroxetine) (p < 0.05). When examining the proportion of complete remitters (CGI-S = 1) after 24 weeks of treatment, there was an increasing treatment difference as a function of baseline HAM-A total score in favour of escitalopram (ITT, LOCF). There was no treatment difference in the low baseline anxiety group. Significantly more patients (p < 0.01) withdrew from the paroxetine group (31%) than from the escitalopram group (17%), partly as the result of significantly more withdrawals due to AEs (p < 0.05). Incidence of AEs and withdrawals were not related to baseline anxiety and there were no significant differences in the incidence of individual AEs with escitalopram compared to paroxetine. LIMITATIONS: The post hoc nature of these analyses, the absence of placebo control group, and the requirement that patients should be suffering from severe depression, limit the generalisability of the results. CONCLUSION: Patients with severe depression together with comorbid anxiety symptoms responded significantly better to treatment with escitalopram 20 mg compared with paroxetine 40 mg. Contrary to paroxetine, escitalopram maintained its efficacy with increasing baseline anxiety levels.

Recurrent brief depression: A frequent syndrome in clinical practice.

Recurrent brief depression (RBD) is not a new artificial group of depression syndromes, but an important, frequently overlooked and clearly identified subcategory of depressive disorders. The symptoms do not differ from major depression; however, the duration of the brief episodes usually lasts 1 - 3 days. The patient can suffer from both brief and longer manifestations of depression and therefore qualify for both diagnoses: major depression on the one hand/or RBD on the other. If the patient suffers from both conditions the case is more severe, with higher social impairment and higher suicidal risk. Epidemiological studies carried out in different parts of the world indicated a prevalence rate of RBD of between 5% and 10% of patients seeking help in general practice. Unfortunately there is no clear treatment as yet established for RBD, although about 50% of these patients are given psychotropic drugs by practitioners. Controlled trials with antidepressants did not show a beneficial effect and there is no hint in the literature as to whether psychological therapies might be helpful. There is a need for further treatment studies in this important form of depression, which is categorizable within the depressive spectrum. ( Int J Psych Clin Pract 2000; 4: 195-199).

Prevalence and recognition of anxiety syndromes in five European primary care settings. A report from the WHO study on Psychological Problems in General Health Care.

BACKGROUND: This study explored the prevalence, socio-demographic characteristics and severity of different anxiety syndromes in five European primary care settings, as well as medical help-seeking, recognition by general practitioners (GPs) and treatment prescribed. METHOD: The data were collected as part of the WHO study on Psychological Problems in General Health Care. Among 9714 consecutive primary care patients, 1973 were interviewed using the Composite International Diagnostic Interview. Reason for contact, ICD-10 diagnoses, severity and disability were assessed. Recognition rates and treatment prescribed were obtained from the GPs. RESULTS: Anxiety syndromes, whether corresponding to well-defined disorders or to subthreshold conditions, are frequent in primary care and are associated with a clinically significant degree of severity and substantial psychosocial disability. Their recognition by GPs as well as the proportion treated are low. CONCLUSIONS: Since people with subthreshold anxiety show a substantial degree of disability and suffering, GPs may consider diagnostic criteria to be insufficient. However, their awareness of specific definitions and treatment patterns for anxiety disorders still needs a lot of improvement both for patients' well-being and for the cost resulting from non-treatment.

The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.

The Mini-International Neuropsychiatric Interview (M.I.N.I.) is a short structured diagnostic interview, developed jointly by psychiatrists and clinicians in the United States and Europe, for DSM-IV and ICD-10 psychiatric disorders. With an administration time of approximately 15 minutes, it was designed to meet the need for a short but accurate structured psychiatric interview for multicenter clinical trials and epidemiology studies and to be used as a first step in outcome tracking in nonresearch clinical settings. The authors describe the development of the M.I.N.I. and its family of interviews: the M.I.N.I.-Screen, the M.I.N.I.-Plus, and the M.I.N.I.-Kid. They report on validation of the M.I.N.I. in relation to the Structured Clinical Interview for DSM-III-R, Patient Version, the Composite International Diagnostic Interview, and expert professional opinion, and they comment on potential applications for this interview.

DSM-IH-R Psychotic Disorders: procedural validity of the Mini International Neuropsychiatric Interview (MINI). Concordance and causes for discordance with the CIDI.

OBJECTIVES: the Mini International Neuropsychiatric Interview (MINI) is a short diagnostic structured interview (DSI) designed to generate positive diagnosis for the main Diagnostic and Statistical Manual (DSM)-III-R/IV Axis I disorders and to explore the symptoms of Criterion A for Schizophrenia (Sc) to rule out the presence of Psychotic Disorders. The procedural validity of the MINI was investigated in psychiatric patients using the Composite International Diagnostic Interview (CIDI) as a gold standard in Europe and the Structured Clinical Interview for DSM-III-R (SCID-P)in the US. This paper presents the concordance and the reasons for discordance between the MINI and the CIDI for DSM-III-R Psychotic and Mood Disorders. No study had systematically analysed the sources of disagreement between DSI based on the same operational criteria in psychotic patients. METHODS: 256 consecutively recruited psychiatric patients and 50 non-psychiatric subjects passed the MINI and the CIDI. RESULTS: concordance was good for the presence of Major Depressive Episode (MDE), Manic Episode, Psychotic Disorders, syndromes or symptoms (0.65 to 0.82). Inconsistencies in evaluation of the disorder recency accounted for 25 to 40% of discordance for current diagnoses. Fifty-three percent of discordance for lifetime Manic Episode resulted from inconsistencies in the severity of the index episode. Fifty percent of discordance for the diagnosis of Psychotic Disorders was due to algorithmic differences between the two DSI. CONCLUSION: the MINI yields reliable DSM-III-R diagnoses within a short time frame (22 minutes). Depending on the quantitative and the qualitative analyses of discrepancies between the MINI and the CIDI for Psychotic Disorders and Mood Episodes, we proposed and tested modifications leading to improvements in both interviews. The procedural validity of the modified MINI according to the modified CIDI was found to be very good.

Characteristics, recognition and treatment of dysthymics in primary care.

As part of the WHO-PPGHC study aimed to better understand the form, frequency and burden of psychiatric conditions in primary care throughout the world, the clinical characteristics of dysthymic patients consulting in primary care were examined. A total of 25,916 general health care attenders at 15 sites in 14 countries were screened using the 12-item General Health Questionaire (GHQ-12). Of those screened, 5,438 were assessed in detail using a Primary Health Care version of the Composite International Diagnostic Interview (CIDI-PHC) in conjunction with among others the Brief Disability Questionnaire (BDQ) and the 28-item General Health Questionnaire (GHQ-28). General practitioners (GPs) gave their opinion on the existence of a psychological problem and indicated what therapeutic intervention was proposed to patients they recognised as psychological cases. The estimated current prevalence of dysthymia as defined by the ICD-10 was 2.1%. The social disability was found to be substantial in patients with dysthymia (52.2% of patients moderately or severely disabled) similar to that observed in patients with Depressive Episode (DE) (57.4%). When both conditions were present, the level of disability was even higher (63.6%). The symptoms presented by dysthymic patients without DE were mostly those specific for the diagnosis of dysthymia (ie, tearful, hopeless, inability to cope, pessimism) while these symptoms were less frequent when dysthymia was complicated by a DE. On the contrary, fatigue and loss of interest were more rarely observed in "pure" dysthymics. In spite of a lower symptomatic severity about half of the patients with dysthymia were recognised as cases by their GPs, a proportion similar to those with DE. However, dysthymics without DE were not, in contrast to patients with DE or with dysthymia and DE, more treated with drugs than non-depressed patients.

Comorbidities in social phobia.

In a sample of 2096 consecutive primary care patients recruited in the Paris region, social phobia was a highly prevalent disorder (5.1%). The most frequent comorbid condition was depressive episode, which affected 70% of patients with social phobia of early onset (at less than 15 years of age), while the highest association was with agoraphobia (odds ratio 10.4). No association was observed with generalized anxiety disorder. Alcohol abuse and suicidal ideation and attempts are also commonly associated with social phobia. However, when patients presented to a general practitioner with comorbid depression present, 76% were recognized as cases (though only 11% were identified as having an anxiety disorder), but in the absence of depression, only 46% were identified as cases. Given the degree of disability caused by social phobia, there is an obvious need for improved education of both doctors and patients regarding its status as a disorder, and its treatability.

Social phobia in primary care: level of recognition and drug use.

A study was conducted in Paris among primary care physicians as part of a World Health Organization study entitled Psychological Problems in General Health Care. Though social phobia is associated with significant impairment and drug use, the level of problem recognition by general practitioners was low. Social phobia (n = 38) was identified as a psychological case in 53% of the patients in whom social phobia was not comorbid with depression, and in 66% when comorbid with depression. This low level of recognition was comparable to that observed for depression where only 66% of the depressed patients (n = 121) were recognized as psychological cases. Psychotropic drug use was high: 61% of patients with social phobia had taken at least one psychotropic drug in the last month, compared to only 32% of those without social phobia. This difference was explained by a significant difference in the use of anxiolytics (45.4 versus 12.1%). The use of psychotropic drugs was twice as frequent in patients with social phobia who were depressed than in those not depressed. The results of this study emphasize the crucial need for primary care physician training in the recognition and treatment of mental disorders.

Social phobia in general health care: an unrecognised undertreated disabling disorder.

BACKGROUND: This study explored the prevalence of social phobia (SP) in general health care, sociodemographic characteristics of patients with SP, the age at onset and severity of SP, its comorbidity with other psychiatric disorders, and the recognition by general practitioners. METHOD: The study was conducted in Paris as part of the WHO study on Psychological Problems in General Health Care. Among 2096 consecutive primary care patients, 405 were interviewed using the CIDI. DSM-III-R diagnoses, severity and disability were assessed. RESULTS: The one-month prevalence of SP is high (4.9) in primary care, although underdiagnosed by GPs. It has an early onset and leads to substantial disability. Patients with SP are at risk of developing further depression, alcoholism or suicidal behaviour. CONCLUSION: SP appears to be a true and frequently severe pathological condition. The awareness of GPs and the general population should be improved.

Recurrent brief depression: clinical and epidemiological issues.

Initially based on empirical observations, the concept of RBD has led to operational diagnostic criteria allowing further studies in various and large populations. In line with the hypothesis of a continuum from normal sad mood to major depression, the spectrum of affective disorders is thus probably more in agreement with everyday clinical practice. Moreover, recurrent and so-called subthreshold conditions have been concurrently investigated in other fields of psychopathology. Nevertheless, many methodological problems and clinical implications of RBD still require further research. The question of a precise definition of the disorder, even if a consensus seems to be obtained about some key points, remains partially to be addressed, for example, concerning the problem of the reliability of assessment. The possibility of a seasonality of the episodes needs further investigations, as do the relationships between RBD and personality disorders such as borderline personality disorder. Finally, the important question of prophylactic treatment of RBD remains unsolved, as antidepressants have failed to demonstrate any efficacy and some neuroleptics have been proposed in particular conditions. Angst's prediction that clinical relevance, impairment, distress and public health impact of affective disorders could be related not only to the duration of an episode but also to the recurrence of episodes, possibly referring to a kindling model, has therefore been confirmed. His major contribution has been to underline, in various forms of affective disorders, the importance of conducting longitudinal clinical as well as epidemiologic studies to refine our psychopathological knowledge.

[Neurasthenia and thymasthenia]. / La neurasthénie et la thymasthénie.

The term of depression applies to two syndromes at least; one is associated with a reduction in interests, activities and with a withdrawal; the other consists of a moral pain, a pessimism, a guilty feeling, an irritability. In each case the depressive mood corresponds to the subjective state. A first survey concerning 3,000 outpatients in general practice allowed us to identify 16.5 of depressed subjects, with 3% showing a pure painful syndrome, 7% showing a syndrome that we described as thymasthenia, and 6% showing the two syndromes (this last group consists probably of major depressive states). This new study, organized by the WHO and concerning 2,000 consecutive patients in primary care, permitted to precise the definition of thymasthenic subjects. The prevalence of current major depressive states is 13.7% and that of dysthymic disorders is 3.6%. Thymasthenia is observed in 9.2% of patients (mean age: 38 years; 60% of women). Among them, 62% show major depressive states, 18% dysthymic disorders, 16% panic disorders, and 11% pure thymasthenia, corresponding to a prevalence of 1%. It should be noted that the prevalence of neurasthenia (according to the definition given by IDC-10) is of 2.9% and that 36% of thymasthenic subjects show also neurasthenia (according to IDC-10). The qualitative content of these two syndromes will be compared.

Prevalence of recurrent brief depression in primary care.

Descriptions of mentally ill inpatients have strongly influenced current classifications of mental disorders. Primary care patients may therefore present a substantially different pathology. Some diagnoses, infrequent in psychiatric settings but common in the general population or in primary care, have been described, such as the concept of recurrent brief depression (RBD) proposed by Jules Angst. RBD refers to frequent but short-lasting (usually only a few days) severe depressive episodes. In parallel with a study organized by the World Health Organization aimed at defining the psychological disorders encountered in primary care, we investigated the prevalence of RBD, its severity, and comorbidity with major and well-defined disorders using a structured interview (CIDI). The current prevalence of RBD in a general practice population was found to be about 10%. The average duration of the episodes is 3-4 days. Ours results confirm the severity of this disorder; in particular, a history of suicide attempts is frequent (23.3%). Among RBD patients, 26% do not present any other psychiatric disorder. When a comorbidity is reported, depressive episodes (lasting at least two weeks, according to ICD-10) and generalized anxiety disorder are the main associated disorders. Our results are in favor of the existence of RBD as a separate and original nosological entity.

The relevance of recurrent brief depression in primary care. A report from the WHO project on Psychological Problems in General Health Care conducted in 14 countries.

This report from the WHO project on Psychological Problems in General Health Care examines the relevance in primary care of the concept of recurrent brief depression (RBD) proposed by Jules Angst. RBD refers to brief, severe depressive episodes that recur frequently, i.e. nearly once a month over a 1-year period, according to Angst. Using a structured interview (CIDI), RBD was assessed in patients not meeting the criteria for depressive episodes lasting at least 2 weeks, as defined in the ICD-10 (DE). A substantial proportion of primary care seekers were identified as presenting RBD without other depressive disorders, 3.7% with a formal RBD diagnosis and 2.7% with frequent but not monthly depressive episodes. These two subgroups were found to differ very little in terms of sociodemographic characteristics, severity, disability, and comorbidity with other diagnoses. However, in patients with a formal diagnosis of RBD, a higher rate of history of suicide attempts was found (14.0%), similar to that observed in patients meeting the criteria for DE. Most of the severity and disability indicators show that RBD is a severe condition, associated with substantial impairment, even if they show a higher degree of severity for DE. About one RBD patient out of three is recognized by general practitioners as presenting a psychological disorder, a majority of whom are actually treated. Our results confirm the relevance of the concept of RBD in primary care, and the need to further explore the pertinence of the restrictive recurrence criterion proposed by Angst.

[Personality of healthy volunteers. Normality and paradox]. / La personnalité du volontaire sain. Normalité et paradoxe.

The personality characteristics of 62 subjects to be screened for eligibility in psychopharmacology studies have been assessed. The psychological screening comprised the Cattell anxiety scale (CAS), the Eysenck Personality inventory (EPI) and the Minnesota Multiphasic Personality Inventory (MMPI) in its complete version (550 items). The comparison of the results to a population matched for age and status showed that the anxiety level was not different, extraversion factor was higher (p less than 0.001) and various personality traits were different. The most striking differences were observed on the factors: Psychopathic deviation, Mania, Schizophrenia greater than controls and social introversion lower than controls. These differences may evoke several biases, such as a recruitment bias or a specific personality pattern of young healthy subjects. In order to discuss these hypothesis, further comparisons with other centers are required to conclude.

[Comparative effects of ginkgo biloba extracts on psychomotor performances and memory in healthy subjects]. / Comparaison des effets d'extraits de Ginkgo biloba sur les performances psychomotrices et la mémoire chez le sujet sain.

The effect on psychomotor and mnesic performances of acute oral dose (600 mg) of 2 Ginkgo biloba extracts were evaluated in twelve healthy female in a dummy placebo-controlled double blind study. Tests were performed comprising: objective measures of vigilance [critical flicker frequency (CFF), choice reaction time (CRT)], memory tasks (pictures and Sternberg scanning tests) and self-rating evaluation (visual analogue scales). Tests session took place before and 1 hour post-dosing. No statistically significant changes from placebo were observed on CFF, CRT or subjective rating of drug effects. No differences between treatment were evidenced on Sternberg scanning test and pictures recognition. Comparing to baseline, free recall score, while decreasing under placebo and Ginkgo, remained the same under Tanakan. As the differences between treatment are localized on one test, it appears important to examine the reproductility in healthy subjects. In order to verify the clinical relevance of these results, they need to be replicated in older healthy volunteers with age-associated memory impairment.