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Biomedical subjects

M F Poirier

Publications and source records attributed to M F Poirier.

At least 37 records · Page 2Linked to original sources
PubMed1999

Venlafaxine and paroxetine in treatment-resistant depression. Double-blind, randomised comparison.

BACKGROUND: About one-third of patients fail to respond to initial antidepressant therapy, which suggests a need for more effective drugs. AIMS: To compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression. METHOD: In-patients or out-patients satisfying DSM-III-R criteria for major depression in evolution for less than eight months, having a baseline HAM-D score > or = 18 and a HAM-D Item 3 score < 3 were eligible. Patients were required to have a history of resistance to two previous antidepressant treatments and a CGI improvement score of 3 at the beginning of treatment. Doses were adjusted to 200-300 mg/day for venlafaxine and 30-40 mg/day for paroxetine. RESULTS: For the observed-case analysis, the response rate was 51.9% for venlafaxine and 32.7% for paroxetine (P = 0.044), and a remission was achieved in 42.3% of venlafaxine-treated and 20.0% of paroxetine-treated patients (P = 0.01). The incidence of adverse effects was comparable between treatment groups. CONCLUSIONS: Venlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population.

Adult↗
PubMed1999

[The concept of resistant depression and therapeutic strategies, particularly, with venlafaxine].

About 30% of depressed patients exhibit depression that is resistant to antidepressant treatment. This resistance may be primary or associated with a concomitant psychiatric or somatic disease. Venlafaxine has shown potent efficacy in certain severe depressions in in-patients and in patients presenting with resistant depression in an open-label study. It was considered of interest to compare, under double-blind, the efficacy of venlafaxine (200 to 300 mg/day) and that of paroxetine (30 to 40 mg/day) (for 6 weeks) in 123 patients presenting with major depression resistant to two correctly conducted antidepressant treatments in the course of an episode of depression of duration not exceeding 8 months. The patients were required not to present with organic disease, particularly endocrine disease. After 28 days of treatment, half of the patients receiving venlafaxine and one third of the patients receiving paroxetine showed a 50% reduction in their total score on the Hamilton scale. In addition, the percentage of patients presenting with remission was significantly higher in the group receiving venlafaxine (42%) compared to that receiving paroxetine (20%). These results require confirmation over the long term and in other forms of resistant depression.

Antidepressive Agents, Second-Generation↗
PubMed1999

[Biological approaches to acute psychoses].

According to the ICD 10 only acute psychotic disorders and transitory acute disorders are specified, whereas DSM IV index, in the same class, schizophreniform disorder, schizoaffectif disorder and atypical psychosis. State biological markers of these disorders are present during the acute episode and disappear with it. A few studies concerns trait predispositional markers of these acute psychotic disorders. In addition, several studies of acute psychotic states are indexed as a partition of usual schizophrenic disorder, as a simple occurrence of that chronic disease. From the biological point of view, dysfunctions of norepinephrine and dopaminergic metabolisms are reported within these acute schizophrenic disorganisation, especially hyperdopaminergia, causality, consequence or evidence of the state syndrome. Those kinds of data are also reported in mood disorder with delusional symptoms. A hypothetic dysregulation of the balance between oxydation and antioxydation system has been searched in these acute states of schizophrenia. From the electrophysiologic perspective, no abnormalities are found for ocular movement functions during these acute psychotic disorders. Besides the clouding of consciousness of confusional states, neuropsychological abnormalities are reported: attention disorders, lack of inhibition of non relevant informations, abnormalities of working memory. Brain imaging can substantiate a diminution of the caudate nucleus size and a possible increase of D2 receptors number. Also, in these acute psychotic states abnormalities of humoral and cellular immunologic system have been found. Lastly, street drugs can originate confusional states and depersonalization, through their serotoninergic, dopaminergic and anticholinergic properties. Ethical drugs can also create an acute psychosis disorder: individual vulnerability and somatic disease cooccurrence act as risk-factors.

Acute Disease↗
PubMed1998

[Current trends in clinical psychiatric research].

SCHIZOPHRENIA: The long-standing dopaminergic hypothesis is based on well-established findings, mainly related to a dysfunction of the mesolimbic C2 and D3 receptors, negative signs of prefrontal hypodopaminergia concerning the D2 and D4 receptors. Immune disorders are also involved as well as a possible neurodevelopmental component. Finally genetic factors play an important role. DEPRESSIVE STATES: Three monoaminergic systems appear to be implicated: the catecholaminergic, serotaminergic and homovanilic systems. It is not known whether the disorder of the serotaminergic system results from pre-existing fragilization or a symptom-related modification. HYPOTHESES CONCERNING DEPRESSION: According to the chronobiology hypothesis, certain biological rhythms (cortisol, temperature, perhaps melatonin) are desynchronized, a disequilibrium which disappears after cure. The fragilization hypothesis is based on the progressive development of a stress-related pathological organization in the hippocampo-hypothalamo-adrenal axis. PERSPECTIVES: The development of new psychotropes remains a challenge to meet the unsatisfied demands in psychiatrics. Drugs with rapid action and minimal side effects are needed.

Brain Chemistry↗
PubMed1998

Plasma melatonin and cortisol in patients with obsessive-compulsive disorder: relationship with axillary temperature, physical activity, and clinical symptoms.

BACKGROUND: Many studies have found biological abnormalities in obsessive-compulsive disorder (OCD), although most of them have not been replicated. The investigation of melatonin rhythm may thus provide an indirect clue to neurotransmitter alterations, and allow a biological comparison with depression. METHODS: The circadian variations of plasma melatonin, plasma cortisol, axillary temperature, motor activity, and obsessive-compulsive symptoms have been documented on a circadian basis in 8 patients with OCD compared to 8 paired healthy volunteers. RESULTS: The circadian pattern of axillary temperature was slightly different in OCD patients when compared to control subjects. No significant difference between the two groups could be observed for any other variable studied. CONCLUSIONS: The discrepancies with previous studies are discussed on the basis of the methods used (patients and control subjects samples, biological measurement procedures). An alteration of temperature circadian rhythm hypothesis is suggested.

Adult↗
PubMed1998

Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence.

Anatomical, pharmacological and human post-mortem studies suggest the dopamine D3 receptor (DRD3) gene as a candidate for drug dependence. We thus performed an association study of the Bal I polymorphism at the DRD3 gene, including 54 opiate addicts and 70 controls. Opiate addicts had a higher sensation-seeking score (on the Zückerman scale) than controls (P = 0.001), particularly a subgroup (70%) who had a distinctly higher score, exceeding 24. There were no marked differences in genotypes between patients as a whole and controls. However, patients with a sensation-seeking score above 24 were more frequently homozygotes for both alleles than patients with a sensation-seeking score under 24 (P = 0.038) or controls (P = 0.034). Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores. This hypothesis is consistent with the role of DRD3 in mediating responses to drugs of abuse in animals and the association of homozygosity at the Bal I polymorphism with drug abuse in schizophrenic patients (see companion article by Krebs et al).

Adult↗
PubMed1998

Dopamine D3 receptor gene variants and substance abuse in schizophrenia.

In an association study of the Bal I polymorphism in the dopamine D3 receptor (DRD3) gene in a French Caucasian population, global comparison of patients with schizophrenia (n = 89, DSM-III-R criteria) and controls (n = 52) led to non-significant differences. However, the homozygosity was significantly more frequent in schizophrenic patients with lifetime substance abuse comorbidity (n = 36) as compared to patients with no history of substance abuse (P = 0.010) or to controls (P = 0.047) and in neuroleptic responder patients as compared to treatment-refractory patients (n = 19; P = 0.037). The combined characteristics treatment response and lifetime substance abuse were strongly associated with homozygosity. We propose that homozygosity for the Bal I polymorphism DRD3 gene is associated with predisposition to substance abuse and/or the pharmacosensitive characteristic of schizophrenia rather than with schizophrenia itself, an hypothesis in agreement with the positive association of this polymorphism with opiate dependence (see companion article by Duaux et al) and the involvement of DRD3 in both pharmacodependence mechanisms and antipsychotic effects of neuroleptics.

Comorbidity↗
PubMed1998

Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol.

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P < 0.03). Conjugated HVA levels slowly decreased during the following weeks (P < 0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P < 0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

Adult↗
PubMed1998

[Psychotropic drugs and behavior].

Behavioral modifications induced by psychotropic drugs result primarily from their pharmacological properties. According to classification of psychotropic drugs, sedative compounds contrast with psychostimulating medications. Behavioural effects of psychotropic drugs depend on dosing, subject's status (patient or healthy volunteer), acute or chronic administration, and environment. Some psychotropic compounds, particularly sedative drugs, decrease the level of mental alertness and cognitive functioning. But those deleterious effects tend to disappear during the course of a repeated administration. Some psychotropic drugs, especially benzodiazepines, induce a tolerance effect, eventually a psychic or a physiological dependence state evidenced by withdrawal reactions. Such similar dependence processes have been reported with other psychotropic drugs. Forensic problems have been attributed to some psychotropic compounds, like benzodiazepines: paradoxical aggressive reactions, psychomotor automatism. Psychotropic drugs usually can confer a positive effect on behaviour owing to their therapeutic action by the way of improving the illness and consequently the life of patients in the cases of depression, anxiety or schizophrenia.

Animals↗
PubMed1997

Manic depressive illness and tyrosine hydroxylase gene: linkage heterogeneity and association.

Several studies have implicated the tyrosine hydroxylase (TH) locus within the 11p15 region in susceptibility to manic depressive illness (MDI). This possibility was further investigated by both parametric (lod score) and nonparametric (affected-pedigree-member and a case-control study) methods of analysis in 11 French MDI families and in a sample of 200 unrelated subjects. Both types of analyses corroborate the implication of this locus, and positive lod scores were obtained in two families, which most likely reflects genetic heterogeneity. Statistical analyses were also performed including available data from published reports. These analyses, which allowed for genetic heterogeneity, substantiated our findings. The combined maximum lod score for all the families studied was 3.68 at theta = 0.00 (number of families: 36) assuming heterogeneity (alpha = 15%, P = 0.01). Taken together these results converge to suggest that the risk factors for MDI lie in the 11p15 region with TH being the most likely candidate gene.

Alleles↗
PubMed1997

Controlled efficacy study of fluoxetine in dysthymia.

BACKGROUND: There have been very few controlled studies of antidepressants in dysthymia, particularly in samples diagnosed reliably and with an adequate length of follow-up. In this investigation, we measured the long-term outcome in a large group of patients meeting DSM-III-R criteria for dysthymia. This study was designed to investigate whether fluoxetine is effective in the treatment of dysthymia. METHOD: This randomised study including 140 patients, compared fluoxetine (91 patients) and placebo (49 patients) on a double-blind basis in two distinct phases: a short-term end-point (3 months with 20 mg/day fluoxetine) and a medium-term end-point (6 months) where the initial responders continued double-blind treatment unchanged and non-responders received an additional treatment of 20 mg/day fluoxetine. RESULTS: After three months of treatment, response was seen more frequently in the fluoxetine group (42/72) than in the placebo group (14/39, P < 0.0001). Improved patients at 3 months were still improved at 6 months. Furthermore, 50% of the nonresponders at 3 months improved and rated as responders at 6 months, after fluoxetine was increased to 40 mg daily. CONCLUSIONS: This study showed the significant and persistent action of fluoxetine on dysthymia. The finding that 50% of the non-responders at 3 months were improved at 6 months, after fluoxetine dosage was increased to 40 mg daily, argues in favour of treating dysthymic patients for at least 6 months, and with a higher dosage if the initial doses are ineffective.

Adult↗
PubMed1996

In vivo characteristics of dopamine D2 receptor occupancy by amisulpride in schizophrenia.

The relationship between the daily oral dose of the benzamide amisulpride and the striatal D2-dopamine receptors occupancy was investigated in 11 schizophrenic patients using positron emission tomography with 76Br-bromolisuride. The patients were studied before and during chronic treatment with amisulpride over a wide range of doses. The test-retest variability of the method was estimated to be 5.8% in a group of four patients receiving placebo. A curvilinear relationship was demonstrated between the amisulpride doses and the D2-receptor occupancy. A range of 70-80% occupancy of the striatal D2 receptors, suggested as an optimal interval for therapeutic action on positive psychotic symptoms, was obtained with doses of amisulpride ranging between 630 and 910 mg per day, while an occupancy of 85%, suggested to be associated with pronounced extrapyramidal side-effects, was reached with 1,100 mg per day.

Adult↗
PubMed1996

Differences in the natural autoantibody patterns of patients with schizophrenia and normal individuals.

The expression of IgG and IgM autoantibodies directed against various autoantigens, either part of the central nervous system or not, was investigated in the sera of inpatients with schizophrenia (n = 10). An enzyme immunoassay was used to measure the levels of these autoantibodies in whole sera, IgG-depleted sera, and isolated IgG fractions. IgG and IgM antibodies, reacting with all the antigens tested, were present in the sera of patients with schizophrenia as well as in the sera of normal individuals. Among patients suffering from schizophrenia, IgM natural autoantibody reactivities could be higher (myoglobin, serotonin, tubulin), lower (dopamine), or even identical to those of normal individuals, depending on whether whole or fractionated sera were assayed and on the group of patients with schizophrenia (responders and nonresponders) considered. The isolated IgG fractions of patients suffering from schizophrenia had higher anti-DNA and antiserotonin reactivities than those detected in normal individuals.

Adult↗
PubMed1995

Sensitive assay of thyroid stimulating hormone in depressed patients.

A decreased thyroid stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) has been noted in major depression. Some authors found a positive correlation between baseline TSH levels and TSH response to TRH, especially with sensitive assays of TSH. Serum TSH was assayed by a sensitive method in 55 depressed patients and 38 healthy volunteers. Patients were subclassified according to DSM-III as suffering from major depression (n = 40) and non-major depression (n = 15). The patients' mean score on the Hamilton Rating Scale for Depression (HRSD) was 50 (SD = 10). The TSH value was significantly lower in depressed patients compared with healthy control subjects, and in major compared with non-major depression. No differences in TSH levels distinguished the various subtypes of major depression. There was a significant negative correlation between global HRSD scores and TSH concentrations. The most anxious patients tended to have significantly lower TSH values compared with the least anxious subjects. Total HRSD insomnia scores correlated negatively with TSH concentrations after log transformation. The sensitive determination of TSH may also provide an index of thyroid function in depression that is simpler to implement than measurements of the TSH response to TRH.

Adult↗
PubMed1995

[Drugs diverted from reaching drug addicts].

To divert from use of psychotropic drugs can take from of a classic toxicomania, sometimes isolated, frequently in association with other toxics: alcohol, opioids. Drugs frequently concerned are anxiolytics: benzodiazepines with a short half-life. Use during more than four months, dependent personality, are risk-factors. Among the other psychotropics, only certain stimulant antidepressants, like amineptine, justify of a particular attention. Drugs of which indication is not psychotropic can induce abuses: more than morphine itself, drugs including opioids or relating are in great demand by drug-addicts: antalgic like dextropropoxyphene or anticough like Neocodion, this one off the prescription. Anorectics, ephedrine vasoconstrictors and beta-stimulants abuse remains frequent.

Amphetamines↗
PubMed1995

A rare allele of a microsatellite located in the tyrosine hydroxylase gene found in schizophrenic patients.

We investigated the frequency of a rare variant of a common microsatellite tetrarepeat allele in the tyrosine hydroxylase gene in 2 independent ethnic groups of schizophrenic patients and their matched controls. In a French population we found the rare variant allele in 5 of 94 (5%) unrelated chronic schizophrenic patients and in none of 145 unaffected controls, thus yielding a significant association (p < 0.01) between schizophrenia and the tyrosine hydroxylase gene. Similarly, in a replication study, we found the rare allele in 4 of 44 (9%) unrelated chronic schizophrenic patients and in none of 44 unaffected controls in a Tunisian population. Albeit the reason of this association is at the moment unknown, it is possible that this polymorphism in the tyrosine hydroxylase gene may be involved in the regulation of its activity.

Adult↗