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Biomedical subjects

Y Lecrubier

Publications and source records attributed to Y Lecrubier.

At least 73 records · Page 4Linked to original sources

[Methodological constraints in evaluating anti-deficit effects].

Several types of limitations are inherent in the evaluation of changes in negative symptoms during clinical trials. Some of these limitations can be listed as follows: the need to select homogeneous study populations (use of a standardized diagnosis), identification of negative dimensions which feature deficitary forms of schizophrenia (qualitative criteria and threshold scores using negative symptom rating tables), strict control of variables which may induce secondary negative symptoms (treatments, other associated disorders particularly of a depressive type, lack of environmental stimulus), follow-up of stability of negative symptoms and, finally, an adequate time interval for evaluation in order to exclude spontaneous and non-specific fluctuations of symptomatology.

Antipsychotic Agents↗

Depression comorbid with anxiety: results from the WHO study on psychological disorders in primary health care.

The World Health Organization collaborative study on "Psychological Problems in General Health Care" investigated the form, frequency, course and outcome of common psychological problems in primary care settings at 15 international sites. The research employed a two-stage case-finding procedure. GHQ-12 was administered to 25916 adults who consulted health-care services. The second-stage assessment (n = 5438) consisted of the Composite international Diagnostic Interview (CIDI), the Social Disability Schedule, and questionnaires. Possible cases or borderline cases of mental disorder, and a sample of known cases, were followed up at three months and one year. Using standard diagnostic algorithms (ICD-10), prevalence rates were calculated for current disorder (one-month) and lifetime experience disorder. Well-defined psychological problems are frequent in all the general health-care settings examined (median 24.0%). Among the most common were depression anxiety, alcohol misuse, somatoform disorders, and neurasthenia. Nine per cent of patients suffered from a "subthreshold condition" that did not meet diagnostic criteria but had clinically significant symptoms and functional impairment. The most common co-occurrence was depression and anxiety. Comorbidity increases the likelihood of recognition of mental disorders in general health care, and the likelihood of receiving treatment.

Adolescent↗

Dysthymia in neurological disorders.

Dysthymia is characterized by long-lasting periods of lowered mood. Epidemiological studies in the USA and Europe have demonstrated that the prevalence of dysthymia is at least 3% of the general population. Its pervasive occurrence makes dysthymia a public health problem worldwide. One feature of this disorder is its co-occurrence with medical and neurological disorders. A World Health Organization meeting on dysthymia in neurological disorders was held in Geneva, 1-3 July 1996 to address this topic. Some of the major goals of this meeting were to clarify the definition of dysthymia in the presence of neurological disorders and to evaluate current research in the field, to point out new areas for investigation, and to discuss current psychological and pharmacological treatments for dysthymia in neurological disorders. The potential roles of neuroendocrine and molecular mechanisms in dysthymia were identified through specific problems related to dysthymia occurring in disorders such as Parkinson's disease, Alzheimer's disease, stroke, multiple sclerosis and epilepsy. This meeting provided direction and opportunity for future studies in the under-recognized and under-investigated relationship between dysthymia and neurological disorders.

Dysthymic Disorder↗

A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers.

OBJECTIVE: To assess the effectiveness of moclobemide on smoking cessation and abstinence in heavy, dependent smokers. There is a strong association between smoking and depression, especially in dependent smokers. It was hypothesized that smoking is a self-medication to treat depression. Cigarette smoke has monoamine oxidase (MAO)-inhibitory properties, and smokers have lower MAO activity than non-smokers. METHODS: We used a randomized, double-blind, placebo-controlled parallel-group study. Placebo or moclobemide, 400 mg/day for 2 months and 200 mg/day during the third month, was given. Main outcome measures were self-reported and biochemically verified (plasma cotinine levels, < 20 ng/ml) abstinence rate. Secondary outcome measures were withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, Hamilton anxiety rating scores, platelet MAO-B activity, and plasma dihydroxyphenylglycol as a measure of MAO-A activity. RESULTS: Eighty-eight smokers were randomized to receive moclobemide (n = 44) or placebo (n = 44). The continuous self-reported abstinence rate was higher with moclobemide than with placebo (intention-to-treat analysis until the end point, 6 months: p < 0.05; until the end of follow-up, 1 year: p = 0.09). The abstinence rate according to plasma cotinine levels showed a trend to effectiveness of moclobemide (end point: p = 0.13; follow-up: p = 0.12). Platelet MAO-B activity increased after smoking cessation but without a significant difference. Plasma dihydroxyphenylglycol levels did not change in the placebo group but decreased dose dependently in the moclobemide group. No difference occurred for withdrawal symptoms, Montgomery-Asberg Depression Rating Scale, and Hamilton anxiety scores. Cessation of moclobemide had no adverse effect. More subjects reported insomnia with moclobemide (n = 16) than with placebo (n = 3). CONCLUSION: In this preliminary study, the reversible, selective MAO inhibitor moclobemide facilitated smoking cessation in highly dependent smokers. Further studies with substantially more smokers are needed to evaluate the role of MAO inhibitors in smoking cessation and abstinence in smokers with high nicotine dependence.

Adult↗

Clinical utility of venlafaxine in comparison with other antidepressants.

The newer antidepressants have clearly shown themselves to be safer and to have a more acceptable side effect profile than the traditional antidepressants. Greater patient acceptability has important consequences in relation to efficacy, in that compliance is likely to be better in the long term. One of the newest antidepressants, the serotonin- noradrenaline reuptake inhibitor venlafaxine, has neurobiologic properties that recommend it for clinical use by both the psychiatrist and the general practitioner. Controlled studies have confirmed the overall utility of this agent in treating a range of depressive subtypes, such as moderate depression and severe endogenous depression, with a low risk of serious adverse events and an excellent tolerability profile. In addition, venlafaxine has shown a dose-response relationship for efficacy, offering the possibility of a wide dose range, which may be suitably employed in different clinical situations.

Antidepressive Agents↗

Moclobemide versus clomipramine in nonmelancholic, nonpsychotic major depression. A Study group.

The efficacy and the safety of moclobemide (400-600 mg/day), a reversible and selective inhibitor of monoamine oxidase-A (RIMA) and of clomipramine (100-150 mg/day) were compared respectively in 98 and 93 nonmelancholic, nonpsychotic out-patients with a DSM-III major depressive episode over 6 weeks and up to 3 months, in a multi-center double-blind trial. No statistically significant difference between the treatments was found on the number of responders, at 6 weeks and 3 months, to the Hamilton Depression Rating Scale (HDRS), which was the main criterion for efficacy. The sample size was sufficient to detect a difference of approximatively 20% in response rates. Reduction of the total scores on HDRS and Covi anxiety scale was comparable for both treatments, but the reduction on the Retardation Depressive Scale (RDS) was significantly higher with moclobemide at the 1- and 2-week assessments. According to the RDS as well as the global impression of both patient and physician, a somewhat earlier onset of antidepressant action was evident in the moclobemide group. Tolerance was significantly better in the moclobemide group, mainly due to a lower frequency of weight gain, sedation and anticholinergic effects.

Adolescent↗

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.

Comorbidity↗

Improvement of some schizophrenic deficit symptoms with low doses of amisulpride.

OBJECTIVE: The authors assessed the effects on primary negative symptoms of low doses of amisulpride, a substituted benzamide neuroleptic with high affinity for D2 and D3 dopamine receptors. METHOD: Young, drug-free schizophrenic patients with pure negative symptoms participated in a 6-week double-blind trial of placebo (N = 10) or low-dose amisulpride (N = 10). They were assessed with the Scale for the Assessment of Negative Symptoms. RESULTS: Amisulpride significantly improved negative symptoms. Improvement in avolition, attentional impairment, and retardation was significantly greater with amisulpride than with placebo. CONCLUSIONS: These findings suggest that some primary negative symptoms may be directly affected by low doses of benzamide neuroleptics.

Adult↗

Treatment of negative symptoms in schizophrenia with amisulpride.

BACKGROUND: The efficacy of low doses of certain neuroleptics in improving negative symptoms is still controversial. This study assessed the efficacy of amisulpride, a benzamide which increases dopaminergic transmission at low doses via presynaptic dopamine receptor blockade, on negative symptoms of schizophrenia. METHOD: The study was designed as a parallel-group, double-blind, placebo-controlled trial. Patients had to fulfil DSM-III criteria for schizophrenia, Andreasen's criteria for negative schizophrenia, and to have a total score of at least 75 on the SANS; those treated with neuroleptics or antidepressants underwent a six-week placebo wash-out. One hundred and four in-patients were randomly assigned to amisulpride 100 mg/d, amisulpride 300 mg/d, or placebo for six weeks; 85 patients completed the study. RESULTS: Both amisulpride doses were significantly more effective than placebo on the primary evaluation criterion (SANS total score, MANOVA P < 0.02). No significant changes were found in positive symptoms or in extrapyramidal symptoms. CONCLUSIONS: Negative symptoms can be improved by low doses of amisulpride, favouring the hypothesis of dopaminergic hypofunction as one of the causes of negative symptoms.

Adult↗

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.

Adolescent↗

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.

Adolescent↗

Central D2 receptors and negative symptoms of schizophrenia.

Most in vivo studies of striatal D2 receptor (SD2R) density with positron emission tomography in schizophrenia have attempted to relate this variable to the diagnosis of the illness. In the present study, a relationship between SD2R and clinical dimensions of this psychosis was searched for in a highly selected group of young negative schizophrenics (8 drug-naïve and 2 drug-free). The SD2R density index measured in vivo using 76Br-bromolisuride and PET correlated negatively (r = 0.80, P < 0.01) with a psychomotor dimension of schizophrenia involving blunted affect and alogia. The mean SD2R index of the patients did not differ from that of age-matched control subjects. Therefore, this behavioural dimension accounts for the variance of the SD2R, suggesting that the striatal dopamine system modulates symptoms such as flattened affect and alogia.

Adolescent↗

Risk-benefit assessment of newer versus older monoamine oxidase (MAO) inhibitors.

The first generation of monoamine oxidase (MAO) inhibitors fell into disuse because of poor efficacy in major depression with melancholia and/or endogenous depression, and because of poor tolerability (drug interactions and the 'cheese' effect). New MAO inhibitors, reversible inhibitors of MAO-A (RIMAs), are able to induce a reversible and specific inhibition of MAO-A. Consequently, the inhibition of MAO is quicker and the dose-response relationship improved, such that dosage adjustment is easier. Also, no carry-over effect once treatment is terminated is observed. The frequency and severity of drug interactions with RIMAs is reduced, although coadministration with pethidine (meperidine) or dextromethorphan should still be avoided. No specific subgroup of patients with depression has shown a better or worse response to RIMAs. The presence of melancholia in major depression, or the existence of endogenous depression, are not predictive of reduced efficacy compared with tricyclic antidepressant (TCA) reference compounds. Dysthymic patients have shown a good response to both RIMAs and TCAs independent of the co-existence of a major depressive episode. Older MAO inhibitors are more effective than TCAs in the treatment of atypical depression, and further studies are needed to confirm if this is true for RIMAs. Long term studies to evaluate the effects of RIMAs on disease recurrence are also required. RIMAs are better tolerated than older MAO inhibitors, including use in subgroups particularly at risk of adverse effects such as the elderly. Overall, RIMAs appear to represent therapeutic progress in the treatment of depression in terms of both efficacy and tolerability.

Depression↗

[Neurasthenia and thymasthenia].

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.

Adult↗

An international study of psychological problems in primary care. Preliminary report from the World Health Organization Collaborative Project on 'Psychological Problems in General Health Care'.

This article describes a large longitudinal multicenter collaborative study that investigated the form, frequency, course, and outcome of psychological problems that were seen in primary health care settings in 15 different sites around the world. The research employed a two-stage sampling design in which the 12-item General Health Questionnaire was administered to 26,422 persons aged 18 to 65 years who were consulting health care services. Of these persons, 5604 were selected for detailed examinations using standardized instruments and were followed up at 3 months and 1 year to provide information on course and outcome. All assessment instruments have been translated into 13 different languages. The project has produced a database that allows for the exploration of the nature of psychological disorders experienced by patients in general medical care and their association with physical illness, illness behavior, and disability over time.

Adolescent↗

A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder.

The selective 5HT3 antagonist tropisetron was studied in 91 outpatients meeting DSM-III criteria for Generalized Anxiety Disorder. Following a placebo washout period of up to 1 week, one of three active treatments (tropisetron 0.5 mg, 5 mg, or 25 mg daily) or placebo was given for a further 3 weeks. After 7 days treatment termination rates due to inefficacy showed a statistically significant dose-related therapeutic effect of tropisetron. Similar effects were seen on the Hopkins Symptom Check List total score and the Global Impression Scale. The Hamilton Anxiety Scale showed a similar trend which, however, failed to reach statistical significance. At day 21 tropisetron showed significant dose-dependent effects on all anxiety-related outcome measures. The incidence of adverse events was low and the severity generally mild. Most frequent complaints were headache, nausea, constipation and nervousness. Laboratory tests and physical examination performed at baseline and study end showed no significant treatment effects.

Adolescent↗