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Biomedical subjects

Jean-Pierre Olié

Publications and source records attributed to Jean-Pierre Olié.

At least 19 recordsLinked to original sources

A prospective study of escitalopram in the treatment of major depressive episodes in the presence or absence of anxiety.

This open, multicenter, prospective study in France assessed the efficacy and tolerability of escitalopram in patients with depression, with or without comorbid anxiety. Escitalopram was administered over a 12-week treatment period to 790 depressed patients, including 482 patients with at least one concomitant anxiety disorder. The study was completed by 649 patients. At baseline, the mean Montgomery-Asberg Depression Rating Scale (MADRS) total score was 31.5 and decreased to 12.4 at end point (last observation carried forward [LOCF]). The MADRS score decreased by 20.5 points in patients with no anxiety disorder and by 18.3 points in patients with at least one concomitant anxiety disorder. The mean Hamilton Anxiety Rating Scale (HAM-A) total score at baseline was 25.6, which decreased to 10.8 at end point (LOCF). The HAM-A score decreased by 13.8 points in patients with no anxiety disorder and by 15.5 points in patients with at least one anxiety disorder. Adverse events were reported by 246 patients (31%). The most frequent adverse events were nausea in 65 patients (8%) and headache in 38 patients (5%); 61 patients (8%) discontinued treatment due to adverse events. Escitalopram was well tolerated and efficacious in reducing symptoms of depression in patients with or without comorbid anxiety over a 12-week treatment period.

Adolescent↗

The French version of the validated short TEMPS-A: the temperament evaluation of Memphis, Pisa, Paris and San Diego.

The TEMPS developed from classical temperament concepts at the Universities of Tennessee (Memphis) and California (San Diego) in collaboration with clinical scientists in Pisa and Paris. It presently exists in 20 languages and full validation of its 110-item version has been accomplished in American English, Italian, French, German, Hungarian, Japanese, Turkish, Lebanese Arabic and Argentinean Spanish. For many studies, a shorter version is easier to use. Accordingly, the 39-item validated English version has just been rendered into French, to facilitate clinical use and research in Francophone countries.

France↗

A kinetic-pharmacodynamic model for clinical trial simulation of antidepressant action: application to clomipramine-lithium interaction.

A generic kinetic-pharmacodynamic (K-PD) model to describe the response to treatment assessed by a clinical score for depressed patients treated by antidepressants alone or combined with a drug that shortens the lag-time before effect was developed. The aims of this study were: (1) to verify model's ability to characterize clinical data, (2) to evaluate several statistics to summarize the clinical effect, (3) to compare the analysis based on these statistics to the conventional intent-to-treat analysis and (4) to determine the optimal dates of clinical assessment. The population K-PD model was fitted to the individual data from a randomized clinical trial assessing the efficacies of clomipramine and placebo or clomipramine and lithium to treat major depression in 141 patients. The K-PD model was able to fit the individual data even in the case of oscillating score profiles. The interindividual coefficient of variation of the model parameters ranged from 33 to 161%. The statistical analysis based on the secondary parameters yielded conclusions comparable to those of the conventional intent-to-treat analysis. The population model was then used for a clinical trial simulation. According to the simulation, the most sensitive summary statistics for detecting a difference between lithium and placebo were the fractional reduction of depression and the proportion of responders. The optimal dates to assess these parameters were day 9 and 11 respectively. The K-PD model might serve as a tool for clinical trial planning in the field of research on antidepressants and their facilitators.

Antidepressive Agents↗

[Legal responsibility of mentally ill persons].

In a long humanistic tradition, insanity is a cause of irresponsibility. An irresponsible patient has to be treated. Are responsibility and irresponsibility so contrasted? Where can we put the limits between judicial repression and mental care? What are the best means to treat mental patients? Debate remains open. This article is a clinical and practical reasoning.

France↗

Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study.

We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms. This multicentre, 12-week, double-blind study randomly assigned subjects with predominantly negative-symptom schizophrenia [i.e. Positive and Negative Syndrome Scale (PANSS) Negative Subscale score >or=6 points greater than Positive Subscale score] to ziprasidone (40-80 mg b.i.d.; n=60) or amisulpride (50-100 mg b.i.d.; n=63). The primary efficacy variable was the change from baseline in PANSS Negative Subscale score. Secondary efficacy variables included change in scores for PANSS Total, Global Assessment of Functioning, Brief Psychiatric Rating Scale derived from PANSS Total and Core, Clinical Global Impression (CGI)-Severity and CGI-Improvement. For the change in PANSS Negative Subscale score, a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline, with equivalence claimed if the lower limit of the 95% confidence interval of the ratio exceeded 0.60. Mean daily dose, adjusted for differential numbers of subjects and differential days between visits, was 118.0 mg for ziprasidone and 144.7 mg for amisulpride. Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects, evaluable subjects (subjects with >or=4 weeks of double-blind treatment and no protocol deviations) and completers in both treatment groups. Ziprasidone demonstrated efficacy comparable to amisulpride in improving negative symptoms and global psychopathology. The groups demonstrated comparable improvements in secondary efficacy variables. Both agents were generally well tolerated, with comparably low incidences of movement disorders. In subjects with negative symptom-prominent schizophrenia, ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity.

Adult↗

Effects of disorganization on choice reaction time and visual orientation in untreated schizophrenics.

Several preattentive mechanisms have proved to be sensitive markers of clinical change in schizophrenia. Two related studies of visuospatial orientation used cued target detection combined with choice reaction time, short/long preparation, with or without a signal/target interval ("gap"/ "no-gap," to detect attentional disengagement difficulty in schizophrenia). End points were reaction times, alertness scores, attentional cost/benefit, and validity scores. Study 1, in 13 schizophrenics receiving second-generation antipsychotics and 13 controls, found the same impairment of disengagement as with neuroleptics, but intact reaction times and processing speed, with no hemispheric asymmetry. Study 2, in 12 untreated acute schizophrenics and 12 controls, showed slower reaction times, near-zero alertness in the fixation release condition, and impaired valid/invalid discrimination versus Syndrome Scale disorganization subscore (r = -0.81; P < 0.01). Early deficits in the preattentive orientation and visual. Early deficits in the preattentive orientation and visual detection phases are useful for assessing response to psychotropic treatment and establishing clinical correlates in acute schizophrenia.

Adult↗

Validity of the CAGE questionnaire in schizophrenic patients with alcohol abuse and dependence.

The objective of the study was to assess the sensitivity and the specificity of the CAGE questionnaire in 114 schizophrenic patients. The Composite International Diagnostic Interview was used to assess the DSM-III-R diagnosis of abuse of or dependence on alcohol. The CAGE questionnaire can be reliably used to assess alcohol use disorders in schizophrenic patients: with a cutoff score of 1 or more, the sensitivity of the CAGE questionnaire was 0.91 and the specificity was 0.83. With a cutoff score of 2 or more, the sensitivity of the CAGE questionnaire was 0.82 and the specificity was 0.94. The post test probabilities (PPV) were high (PPV1=0.74; PPV2=0.85) compared to the primary probability of alcoholism (29.8%).

Adult↗

Age at onset of schizophrenia: interaction between brain-derived neurotrophic factor and dopamine D3 receptor gene variants.

One of the main features of schizophrenia is its age at onset in early adulthood. Dopaminergic dysregulation is the most documented neurobiological factor that may be involved in triggering schizophrenia. Recent findings on neurodevelopmental processes show that the brain-derived neurotrophic factor plays a critical role in the development of mesolimbic dopaminergic-related systems and regulates the expression of dopamine D3 receptors. In this study, we examine whether an interaction between dopamine D3 receptors and brain-derived neurotrophic factor gene variants influences age at onset in patients with schizophrenia. Our findings show that this gene-gene interaction was significantly associated with an earlier emergence of psychosis by 3 years.

Adult↗

[Management of bipolar disorders].

Management of the bipolar disorders is well codified and rests on the prescription of mood stabilisers and psychotherapeutic measures. Mood stabilisers have considerably improved the prognosis of bipolar disorder, in limiting the number of recurrences. Lithium is still the leader of mood stabilisers. It has a preventative and curative action that has effect on the two poles of the illness. Carbamazepine, valpromide and its derivatives, and olanzapine are indicated in the case of resistance or contra-indication to lithium therapy and are more easily handled in the curative treatment of the manic state. Other therapeutic measures have been proposed in order to optimise the medical treatment and to act in anticipation of the precipitating elements. Psycho educational measures, the roles of which have been undervalued for a long time, are today the best-evaluated psychological treatments. An elevated level of proof exists for these treatments. Their value is stressed in most of the reference texts. The benefits of this complementary approach exists on different levels: early recognition of symptoms that announce a recurrence, improvement in compliance, acceptance of the illness, better management of the social life, both professional and emotional, control of precipitating factors... Recently published studies report a reduction in the number of recurrences and relapses, a reduction in the duration of hospitalisation, a better balance in the family life and an improvement in compliance.

Antimanic Agents↗

[Schizophrenic disorders: current etiologic and clinical knowledge].

Brain anomalies associated with schizophrenic disorders may be of a cognitive, neurophysiological or neurological nature [the latter being relatively minor and nonspecific]. Brain imaging has revealed early anomalies such as cortical-subcortical atrophy and abnormal gyration. These anomalies can also be present in relatives free of schizophrenic symptoms. This raises the question of what determines the transition from vulnerability to clinical onset. There is now evidence that schizophrenic disorders are true brain diseases. This is based on neuropathological studies, brain imaging and clinical findings such as "soft" neurological signs (pyramidal and extrapyramidal symptoms, coordination difficulties, etc.). Cognitive dysfunctions such as attention and memory disorders and abnormal verbal fluency have also been described. Oculomotor pursuit and auditive evoked potentials have identified specific neurophysiological disorders such as N300 and P50 wave modifications. Schizophrenic disorders can also be associated with neuronal abnormalities, notably affecting factors involved in synaptic transmission and plasticity. For example, BDNF protein deficit is linked to certain late-onset forms of schizophrenia. Genetic studies are no longer focusing on a possible disease genotype but rather on phenotypic characteristics determined by simpler genotypes (P50 wave modulation, COMT and BDNF genes). The ultimate objective is to identify high-risk subjects, in order to shorten the treatment delay and thereby improve long-term outcome. The benefit of primary prophylaxis remains to be determined, however.

Brain↗

Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia.

Schizophrenia is associated with impairments in many cognitive domains on which the influence of antipsychotics, whether conventional or atypical, remains unclear. We conducted a study of recent-onset schizophrenic patients (DSM IV) that included unmedicated (n=19), and medicated (n=19) patients matched for age and IQ. Both groups of patients had comparably low extra-pyramidal symptoms (EPS). Cognitive tasks included attentional tasks (alertness and divided attention tests), a working memory task (a verbal n-back test) and the Wisconsin Card Sorting Test (WCST). After adjustment for the Total PANSS score, we found no significant difference between the two groups of patients in any of the cognitive tasks. When compared to a group of healthy controls (n=20) matched for IQ level, unmedicated patients performed significantly worse in all cognitive tasks, with significantly longer reaction times for alertness, divided attention and working memory. These results confirm the presence of cognitive impairments in attentional and executive functions in recent-onset patients whether or not they are medicated. There was no evidence that either conventional or atypical antipsychotics had an influence on patients when EPS were excluded. Altogether, our results further support the idea that cognitive deficits in schizophrenia are enduring features per se and cannot be considered as secondary to psychiatric symptoms or to the adverse effects of medication. In addition our results suggest that antipsychotics do not have a major effect on these impairments.

Adult↗

Nicotine use in schizophrenia and disinhibition.

The role of personality in nicotine use has been little studied in patients with schizophrenia. The objectives of the present study were to compare impulsivity, sensation seeking and anhedonia in a group of schizophrenic patients with and without current cigarette smoking. One hundred patients with schizophrenia or schizoaffective disorder (DSM-III-R criteria) were assessed with the Positive and Negative Syndrome Scale, the Fagerström Scale, the Barratt Impulsivity Scale, the Zuckerman Seeking Sensation Scale, and the Chapman Physical Anhedonia Scale. Among these patients, 67% were current smokers. The mean scores for sensation seeking were higher in the group of smokers than in the group of nonsmokers. The differences were found exclusively with the "disinhibition" subscale. No significant difference was found for impulsivity and physical anhedonia mean scores. The scores on the Sensation Seeking Scale were especially low in nonsmokers. Cigarette smoking could influence disinhibition and possibly help to normalize inhibition in schizophrenic patients.

Adult↗

Cerebellum development and schizophrenia: an association study of the human homeogene Engrailed 2.

Epidemiological data and family studies in schizophrenia show that genetic factors contribute to the vulnerability to this disorder. The homeogene Engrailed 2 (EN2) is specifically involved in patterning the region that gives rise to the cerebellum and controls the plasticity of midbrain dopaminergic neurons. We carried out an association study for a CA repeat polymorphism located in the 3' region of the homeogene EN2. The subjects consisted of 165 patients with schizophrenia and 97 controls matched for age and ethnicity from a French Caucasian population. We found no significant association of schizophrenia with this bi-nucleotide repeat polymorphism of the EN2 gene.

Adult↗

Effects of atypical neuroleptics on alertness and visual orienting in stabilized schizophrenic patients: a preliminary study.

It has been shown that schizophrenic patients treated with conventional neuroleptics display a general slowness in latency in simple reaction-time tasks and a disengagement deficit in visual-orienting tasks. Yet, the influence of atypical neuroleptics on attention is still controversial. The purpose of our study was to investigate the effect of atypical neuroleptics in tasks requiring alertness, selective attention or visual orienting. Thirteen stabilized schizophrenic patients receiving atypical neuroleptics were compared to 13 healthy controls matched for age, gender, and study level, in a choice reaction time (CRT) task and a visual-orienting task cued target detection (CTD) task. The results showed that patients and controls obtained comparable reaction times (RTs) in the CRT task. In the CTD task, both groups had comparable RTs but the presence of invalid cues caused a greater attentional cost in both visual fields for patients compared to controls, indicating a symmetrical disengagement deficit. To conclude, patients treated with atypical neuroleptics had a phasic alertness ability similar to controls. By contrast, an impairment of disengagement was present in those patients. Thus, atypical neuroleptics could have a positive influence on certain but not all attentional domains.

Adult↗

[Depression and aging].

Depression is one of the most common health disorders in elderly people. It is still often considered as a natural consequence of aging, arising in reaction to a medical disease, cognitive or functional decline, or a loss of social fabric. Many studies have highlighted the low rates of diagnosis and treatment of depression, especially in the primary care setting. Major depression in old age is characterized by the same core symptoms as in other periods of life. However, aging may accentuate some symptoms and alleviate others. Somatic concern, marked anxiety, poor subjective memory, psychotic ideation, and recurrent thoughts of death can mask sadness and anhedonia. Organic factors and adverse life events are often intricately linked with the pathogenesis of depressive states in the elderly. The role of cerebrovascular lesions has also been established, particularly in late-onset depressive disorders. The management of depressive disorders in older people, as in younger adults, involves pharmacological and psychological treatments. Electroconvulsive therapy can be beneficial in some cases. Transcranial magnetic stimulation is being evaluated in this setting.

Aged↗