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Biomedical subjects

P Bizouard

Publications and source records attributed to P Bizouard.

At least 19 recordsLinked to original sources

Tricyclic antidepressant-induced extrapyramidal side effects.

Two cases of tricyclic antidepressant-related extrapyramidal side effects are reported and, the authors review the literature describing these effects. Despite clear case reports, these side effects are not well known. Given the wide prescription of tricyclic antidepressants (TCA) and the low number of case reports, the prevalence of these side effects is indeed low, but clinical implications exist. The extrapyramidal symptoms induced by TCA alone are acute or tardive dyskinesia, akathisia, myoclonus, rabbit syndrome and dystonia. These symptoms seem to be non age-related, but often dose-related, and were responders to antiparkinsonian agents or propranolol. The factors that predispose an individual to the development of these side effects are not completely understood. Some risk factors such as prior exposure to neuroleptics and/or lithium or estrogens could facilitate the development of these side effects. In some cases, they can disappear even though the same dose of TCA is continued, and they do not seem to be a drug class reaction. The susceptibility of each individual patient to the development of these disorders may be limited to only one or a few of these agents.

Adolescent

Paroxetine and galactorrhea.

The authors report a case of galactorrhea following antidepressant treatment where paroxetine might be responsible. Paroxetine is a selective serotonergic reuptake inhibitor (SSRI). Galactorrhea occasionally is a dopamine-mediated side effect observed with neuroleptic drugs. However, the ability to produce extrapyramidal side effects is known for tricyclic as well as for SSRIs. Thus the potential of SSRIs to induce dopamine-dependent side effects is a clinical reality and it was not surprising to observe galactorrhea due to paroxetine. However, in a review of the literature no reported cases of galactorrhea associated with paroxetine were found.

Adult

[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

CYP 2D6 PM phenotype hypothesis of antidepressant extrapyramidal side-effects.

Extrapyramidal symptoms occur as side-effects of neuroleptics. For many years, case reports of such side-effects, linked to antidepressant treatments, have been published, but this phenomenon is not well known. Tricyclic and serotonergic antidepressants are both involved. The authors present an hypothesis which provides one possible neurobiochemical explanation for the aetiology of these side-effects. The proposed explanation is related to the inhibition of the CYP 2D6 isoenzyme by antidepressants (or neuroleptics) that may be involved in the genesis of the observed extrapyramidal side-effects.

Antidepressive Agents

Fluvoxamine and fluoxetine: interaction studies with amitriptyline, clomipramine and neuroleptics in phenotyped patients.

The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day(-1)) or fluoxetine (20 mg day(-1)). A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P<0.01) with fluoxetine and from 0.34 to 0.84 with fluvoxamine (P<0.05). The (dextromethorphan) 'extensive metabolizer' phenotype switched to the 'poor metabolizer' phenotype in six patients by the 10-day fluoxetine treatment, and in two patients by the fluvoxamine treatment. The mean S/R increased from 0.24 to 0.34 (P<0.05) with fluoxetine, and from 0.33 to 0.58 (P<0.002) with fluvoxamine. These results are in agreement with the observed modification of TCA plasma levels after the SSRI association. During fluvoxamine treatment, amitriptyline and clomipramine plasma levels (P<0.06 both) tendentially increased, and those of demethylclomiprarnine decreased (P<0.06). Fluoxetine addition lead to a significant increase (P<0.02) of the desmethylclomipramine plasma levels. Fluvoxamine induced a moderate augmentation of the plasma levels of haloperidol and its reduced metabolite and no change in the plasma levels of cyamemazine and levomepromazine. But patients treated with neuroleptics are to few to draw any firm conclusion. This study suggests, that fluoxetine and fluvoxamine differ in their interaction with the metabolism of some other basic psychotropic drugs, by a mechanism which implies CYP2D6 and CYPmeph and possibly other isoformes of cytochrome P-450. Moreover, the interactions produced varied with the TCA prescribed.

Adult

[Value of plasma assays of psychotropic drugs].

An increased use of determinations of psychotropic drug levels has been noted during recent years. The contribution of "biological techniques" has led to a change in the relationship between physician and patient by rationalizing medical prescription and by augmenting the medical nature of this relationship. Follow-up of plasma levels is of interest for psychotropic drugs having therapeutic and (or) side effects that are linked to blood concentrations. Such drugs include the imipraminic antidepressants and regulators of thymic function. There is no consensus concerning the benzodiazepines and neuroleptic drugs. Their clinical effect does not seem to be strictly linked to plasma levels and the range of dosages is greater. Such determinations have proved to be particularly interesting in "resistant" cases, in surveillance of drug interactions and to evaluate treatment compliance.

Causality

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

[Prediction of suicide risk].

Suicide is a great problem for public health. In France it causes more than 12,000 deaths every year, and it has been estimated that 45 to 70% of these subjects were suffering of affective disorders. Some epidemiological aspects of the links between suicide and depression are analytic and concern the risk factors of suicide among depressed patients: sociodemographic factors: risks are more important for men and for people living alone or suffering of social and affective isolation. Violent suicides increase with age; clinical and evolutive characteristics of the illness: the risk of suicide is correlated with the global severity of the depression, whatever are the nosographic subtypes, with anxiety, sleep disorders and anhedonia, with personal and familial history of suicide; among biological factors, a decrease of 5-HT transmissions has been implicated, but it seems to be more correlated with a modification of the ability to delay, with a poor impulse control. The association of several of these factors increases suicidal risk but it is impossible to describe a specific picture of the depressed suicidal patient, and clinical scales to estimate suicide risk are of limited interest. Finally, the clinical vigilance adapted to each individual case and the quality of the therapeutical relation remain the most important point for preventing suicide.

Causality

[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