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P Vandel

Publications and source records attributed to P Vandel.

31 records · Page 2Linked to original sources
PubMedDate not supplied

Drug extrapyramidal side-effects or not: is there a dextromethorphan phenotype difference?

A recent hypothesis suggests the possible role of cytochrome P450 2D6 (CYP2D6) polymorphism (involved in the metabolism of a large number of drugs), as a potential risk factor for the development of extrapyramidal side-effects of psychotropic drugs. The CYP2D6 metabolizer phenotype (dextromethorphan test) of 31 drug treated psychiatric adult patients suffering from extrapyramidal side-effects (group 1) and of 31 matched patients without drug side effects (group 2) were compared. In the first group, 13 poor metabolizer patients (41.9 per cent) were found, characterized by a dextromethorphan metabolic ratio > 0.3, and only two patients in the second group (6.4 per cent). These data provide some support for the notion that in subjects in whom CYP2D6 is probably saturated, the risk of drug extrapyramidal side-effects may be increased. In such patients the choice of psychotropic drugs 'without' this risk must be preferred.

Adolescent↗
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↗
PubMedDate not supplied

[Fluoxetine and tricyclic antidepressants: clinical tolerance in short-term combined administration].

The tricyclic SSRI antidepressant association is often used in the treatment of resistant depressive illness. The pharmacokinetic interaction existing between these two types of drugs is well known, with as result, an increase of tricyclic antidepressant plasma levels. The aim of this work was to assess the clinical tolerance of the association of fluoxetine and tricyclic antidepressants, prescribed at usual doses. In 10 patients, having a bad response to a tricyclic antidepressant treatment, with in the therapeutic window adjusted plasma levels since 3 weeks, an association of fluoxetine (20 mg/d) to the tricyclic was prescribed. The other associated treatments were unmodified. The clinical evolution was recorded with the MADRS and the UKU scale for side effects, before the tricyclic antidepressant treatment adjustment (D-21) and just before the fluoxetine association (D1) and every 7 days after this association too. The tricyclic plasma levels (amitriptyline and clomipramine) and the patient phenotype CYP 2D6 and 2C19 were determined before and 7 days after the fluoxetine addition. A good clinical evolution was noted since the 7th day after the fluoxetine association to tricyclic (mean MADRS scores on D-21, D1, D7 and D14; 35.4, 33.1, 23.9, 16.8 respectively). In 3 patients, an anxiety increase on day 6, 14 and 16 respectively, after fluoxetine addition, induces a stop of the serotonergic antidepressant. In one patient all the treatment was stopped due to the appearance of a mood inversion. In another patient, after 14 days of antidepressant association, EC were prescribed as asked by the patient, due to an insufficient mood improvement, with a good clinical result and tolerance. The evolution of the side effects was surprising. There was no increase of the UKU score mean during the associated treatment, despite an increase of the tricyclic plasma levels that reached, in three patients, the toxic level (510, 605 and 860 ng/ml of amitriptyline + nortriptyline or clomipramine + demethylclomipramine). The UKU psychic score mean significatively decreased (7.7, 6.8, 5.3, 4 on D-21, D1, D7, D14 respectively). The fluoxetine association did not modify the neurological, neuro-endocrinologic and the skin side effects. None increase of headheck was noted. The increase of anxiety, observed in 3 patients, was not considered as a side effect of the antidepressant association, but an effect of the stimulant potency of fluoxetine in anxious patients. The pharmacogenetic results confirmed the strong inhibition potenty of fluoxetine on the CYP 2D6 isoenzyme. In 5 patients indeed, the extensive metabolizer phenotype was modified in a poor metabolizer phenotype, seven days after the association of fluoxetine. The CYP 2C19 phenotype was unchanged after this association. The patient phenotype did not seem to interfere with the clinical results. In conclusion, in this group of patients, the short-term clinical tolerance of the tricyclic antidepressant and fluoxetine association was very good, despite the pharmacokinetic interaction existing between these two types of drugs.

Adult↗