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Biomedical subjects

S Nezelof

Publications and source records attributed to S Nezelof.

16 recordsLinked to original sources
PubMed2004

Clomipramine, fluoxetine and CYP2D6 metabolic capacity in depressed patients.

Cytochrome P450-2D6 may be involved in the metabolism of many drugs such as psychotropic drugs and its genetic polymorphism is responsible for inter-individual differences in the therapeutic effect and toxicity of these drugs. Moreover with the same genetic basis, CYP2D6 metabolic capacity variations are observed. Different factors of variation may be involved, among them the prescribed drugs. The aim of this study was to compare the influence of two types of antidepressants, tricyclic (clomipramine) and serotonergic specific recapture inhibitor (SSRI) (fluoxetine), on the CYP2D6 metabolic capacity of depressed inpatients. The CYP2D6 phenotype (dextromethorphan test) was determined in 56 genotyped (PCR-SSCP) depressed caucasian inpatients with a heterozygous genotype. Forty-five subjects were treated with clomipramine and eleven received fluoxetine. The dextromethorphan metabolic ratio (MR) median was significantly higher in the fluoxetine group (0.255) than in the clomipramine group (0.083, p < 0.014). In this study, fluoxetine involved a greater decrease of CYP2D6 metabolic capacity than clomipramine. Clinical implications and the possible connection between a decreased CYP2D6 activity and adverse drug effects were discussed. Caution should be taken when drugs with a low therapeutic index must be coprescribed in such patients.

Adolescent↗
PubMed2001

Psychoactive substance consumption in eating disorders.

Research investigating the comorbidity between eating disorders and substance-use disorders have reported positive but contrasting results. The aim of this study was to further explore this association by studying patterns of consumption of the entire range of psychoactive substances (alcohol, specific drugs, prescribed psychotropics) in a large sample (N=271) of eating-disorder DSM-IV subtypes. Results show that subjects suffering from anorexia of the restrictive type show significantly less drug-consumption behaviors and alcohol abuse and/or dependence disorders than purging anorexic and bulimic subjects. No difference was found in the total consumption of psychotropics among the four groups of eating disorders. However, more than half of eating-disorder subjects are regular consumers of psychotropics. Among these regular consumers, bulimics self-prescribe and increase their doses of psychotropics significantly more than anorexics. Features of impulsivity that are associated with purging and bulimic behaviors could play a specific role in these patterns of comorbidity and account for such differences.

Journal Article↗
PubMed2001

[Psychoactive drug use in a declared non-addicted control sample and comorbidity. Results of a study in 860 French-speaking subjects].

AIMS: This study, conducted within the framework of a broader research program of the INSERM 494013 Dependence Network, was designed to estimate illicit drug use and tobacco smoking in a declared non-addicted sample and to determine whether illicit drug users differ from non-users in terms of comorbidity. METHODS: The study was conducted in an "all and sundry" sample of subjects. Patterns of drug use and comorbid factors (psychiatric disorders, suicide attempts, repeated accidents, social inadaptation) were assessed using a semi-structured interview (heteroevaluation, MINI DSM IV interview, Gröningen). RESULTS: Among 860 subjects, 107 (12.4%) used illicit drugs and 26 of these 107 (24.3%) were dependent users or abusers. Specific analysis of non-dependent non-abuser subjects who had used illicit drugs (70 occasional and 11 regular users) showed a higher rate of use in younger subjects (12.7% in the 15-24 year group, 5.7% in the 24-49 year group) and men. Except for repeated accidents (OR=5.5 [1.6-18.5]), comorbid disorders were not more frequent in non-users than in users. CONCLUSION: Besides use for recreational purposes, the rate of use of illicit drugs with abuse or dependence was high in our non-clinical sample. Although no specific comorbid psychiatric disorders were identified among non-dependent non-abuser subjects who had used illicit drugs, the frequency of repeated accidents evidenced the ill-fated side effects of illicit drugs and/or the specific biopsychological vulnerability of these subjects. This highlights the importance of not neglecting drug abuse.

Accidents↗
PubMed2000

[Pertinence of the addiction concept in eating behavior disorders].

From a psychodynamic perspective, dependence disorders, irrespective of the object of addiction, can be seen as the expression of the subject's neurobiological, psychopathological, cultural and social vulnerability. Since vulnerability strengthens and reorganizes the personality, it can drive these subjects to perpetuate pathological behaviors. In this light, behavior disorders belong to the field of addiction diseases, especially considering that the underlying psychopathological structures are close to those observed in addiction, that depression plays a central role, and that their development into toxic addictive behavior (drugs, alcohol, psychotrope) is frequent.

Adolescent↗
PubMed1999

Drug extrapyramidal side effects. CYP2D6 genotypes and phenotypes.

OBJECTIVE: Among Caucasians, a lack of cytochrome P450 enzyme CYP2D6 is observed in 5-10% of individuals, named poor metabolizers (PMs). A consequence may be an impaired metabolism of many drugs such as most of the psychotropic drugs with an increased risk of drug side effects. This enzyme is also involved in the metabolism of endogenous compounds, including neurotransmitters such as dopamine and dopamine-related neurotransmitters which play a role in the mechanism of action of extrapyramidal drug side effects. The present study investigates whether patients who have developed and those who have not developed extrapyramidal drug side effects differ in their CYP2D6 genotypes and phenotypes. METHODS: The CP2D6 genotype (method involving restriction length fragment polymorphism and polymerase chain reaction-single strand conformation polymorphism) was determined in 65 drug-treated in-patients, and the CYP2D6 phenotype (with dextromethorphan probe) in 62 of them. Two groups were constituted, one with 22 patients who had developed extrapyramidal drug side effects, and the second with 43 patients without such side effects. RESULTS: In the whole population, there was an over-representation of PM phenotypes--more marked in the first group than the second (45% vs 14%). Concerning the genotypes, we observed that the percentage of functional alleles (with extensive metabolic capacity) was higher in group 2, whereas the percentage of nonfunctional alleles (without metabolic activity) was higher in group 1; this frequency difference was only marginally significant (chi 2 5.95; P < 0.0509; degrees of freedom = 2). Consequently, there was a higher percentage of genotypes with no (extensive) functional alleles in the group of patients suffering from extrapyramidal side effects than in the other group (P < 0.00001). CONCLUSION: CYP2D6-impaired metabolic capacity may be a contributory factor in extrapyramidal drug side effects.

Adolescent↗
PubMed1997

[Indications for electroconvulsive therapy].

ECT, in which first experiments were made by the italian Cerletti more than half a century ago, underwent, in the seventies, a definite decline, as it was less and less applied to patients, a result of the influence of anti psychiatry. During the last fifteen years, there has been a legitimate renewal of the interest for this therapy; its indications seem now well codified and its techniques and practises have evolved considerably. Actually, in order to carry out ECT under general anaesthesia, it is necessary to have a pluridisciplinary team, assembling nurses, anaesthesists and psychiatrists that will use more and more effective appliances and adequate anaesthetics. Many of the parameters able to influence ECT's effectiveness are now well known and can be used and adapted according the individual characteristics of each patient. These parameters are: the lateralisation of the electrodes, the intensity of the electric current, the duration of the epileptic fit, the modification that appear in electroencephalography and the frequence of the sessions. According to different investigations, it seems that we must systematically question the medical treatments we associate to ECT. For instance, it is highly recommended not to prescribe with ECT benzodiazepines or antiepileptic mood stabilizers, while antidepressants or neuroleptics do not seem to exert any influence on the effectiveness of the treatment. Some authors think caffeine and triiodothyronin (T3) could have an interesting effect when combined with ECT. As to the indications of shock therapy, they can be now more and more precisely defined making of this treatment an indispensable instrument in the cure of depressive disorders. But ECT is also appropriate in maniac disorders once neuroleptic treatment has failed or else in the very beginning in highly acute cases, and mainly in mixed episodes for which medical treatment is often difficult to adapt. In schizophrenia, ECT can also be prescribed in definite circumstances as catatonia, paranoid states or schizoaffective episodes. Therefore, ECT constitutes a safe and comfortable therapy for the patient since its side effects are essentially characterized by cognitive disorders, and its main contraindications consist of severe cardiovascular diseases. ECT is also an essential tool in some definite cases.

Antidepressive Agents↗
PubMed1992

Tricyclic antidepressant plasma levels after fluoxetine addition.

After a review of a pharmacokinetic interaction between tricyclic antidepressants (TCA) and fluoxetine the authors report their own data. They confirm the existence of an interaction of TCA with fluoxetine, in clinical practice, but the fluoxetine was not associated in all cases with a marked increase of TCA plasma levels. The increase appeared especially high with clomipramine (n = 4) and imipramine (n = 3), and lower or dose-dependent with amitriptyline (n = 4). The pharmacokinetic change did not induce side effects in the patients, even when the total TCA plasma level increased to 965 (clomipramine) or 785 (imipramine) ng/ml. The authors then discuss the clinical implication and the possible mechanism of action.

Adult↗
PubMedDate not supplied

[Consumption of benzodiazepines in a university hospital center].

Benzodiazepine consumption has been studied in an inpatient population of a hospitalo-universitary center. The different user wards were classified by their cost or the importance of their benzodiazepine use. In a second step, the authors studied the prescription in the 6 most consumer medical wards. The most prescribed benzodiazepines were lorazepam and dipotassium clorazepate (27 and 23% respectively). In these six wards, on the day of the study, 48% of the 227 inpatients were taking benzodiazepines. Fourteen out of them were taking more than one of these drugs. In 80% of the cases, the patient was asking for the prescription. Out of the 110 inpatients found to have taken a benzodiazepine on the day of the study, 74 had already regularly used it during the years before hospital admission, mainly women (64%) and old people. Finally, out of the 227 inpatients studied, the hospitalization is a possible inducer of the benzodiazepine intake and dependence in 16% of the patients. The results are discussed against the background of other studies concerning benzodiazepine consumption.

Adult↗
PubMedDate not supplied

[Undesirable effects of drugs. Epidemiologic study at a psychiatric service of a university hospital].

The authors reviewed the drug side effects observed in their ward during the 5 last years (1988-92). These alleged effects occurred at a very low incidence, 3 per cent, (116 cases on 3809 hospitalizations). As mentioned in the literature, the occurrence was higher in females (60 per cent), than in males. The age seemed not to be a risk factor in that population, the mean age being 44 for the men and 45 for the women. All side effects disappeared after decreasing or stopping the suspected drug. In 6 cases the suspected drug was not a psychotropic agent. The authors presented some of the more often reported cases, and some of the more recently known, such as extrapyramidal side effects with antidepressants, increase of the libido with serotonergic antidepressants. The problem fo polytherapy is discussed. In half (59/116) of the cases there was a psychotropic association. The side effect may be due to a pharmacokinetic interaction in 16 cases, either with enzymatic inhibitors like dextropropoxyphene, valpromide, valproic acid, fluvoxamine and fluoxetine, or with enzymatic inducers like carbamazepine. The authors compared the side effects of the antidepressants mainly used in their ward (amitriptyline, clomipramine, fluvoxamine and fluoxetine).

Adult↗