[Is depressive disorder linked to anxiety disorder among anorexics and bulimics?]. / L'existence d'un épisode dépressif majeur est-elle liée à la présence de troubles anxieux chez les anorexiques et les boulimiques?

UNLABELLED: The primaty objective is to determine whether the presence anxiety disorders is related to depressive comorbidity in subjects suffering from ED, while taking into account certain variables which may be related to depression [subjects' age, ED duration, prior incidents of anorexia nervosa in BN subjects, inpatient or outpatient status, nutritional state (as measured by Body Mass Index or BMI)]. Our secondary objective is to evaluate the relative chronology of the onset of anxiety disorders and depressive disorders in anorexic and bulimic subjects. METHOD: We evaluated the frequency of depressive disorders in 271 subjects presenting with a diagnosis of either anorexia nervosa or bulimia, using the Mini International Neuropsychiatric Interview (MINI), DSM IV version. RESULTS: While univariate analyses show that nearly all anxiety disorders are related to major depressive episode (MDE), a separate analysis of each anxiety disorder reveals that they do not all have the same influence in terms of risk of onset of MDE in anorexics and bulimics, when adjusted for univariate variables related to MDE (subjects' age, ED duration, prior incidents of anorexia nervosa in BN subjects, inpatient or outpatient status, nutritional state). Current generalized anxiety is significantly related to lifetime presence of MDE in AN subjects, and to current MDE in AN and BN subjects. Generalized anxiety is the most frequent disorder in AN and BN subjects to according our study; it also appears to be one of the principal predictive factors for MDE, which is 2.4 to 4.2 times more frequent when GAD is present. Diagnosis of OCD has its own particular effect on lifetime risk for MDE in AN subjects, regardless of GAD: it increases the risk of depression by 3.5. It is one of the most frequent anxiety disorders among AN subjects, present in nearly a quarter of them. In bulimics, when GAD is excluded, two factors are related to current diagnosis of MDE: panic disorder and subjects' inpatient or outpatient status. Hospitalized bulimics are diagnosed with current MDE 4.4 times more often than those seen as.

[Are anxiety or depressive disorders more frequent among one of the anorexia or bulimia nervosa subtype?]. / La fréquence des troubles anxio-dépressifs diffère-t-elle entre les types diagnostiques d'anorexie mentale et de boulimie?

UNLABELLED: Our objective was to answer the following question: are there differences between diagnostic groups of eating disorders (ED) for the prevalence of depressive and anxiety disorders, when clinical differences between the groups are taken into account (ie age of subjects, ED duration, inpatient or outpatient status, and Body Mass Index)? METHOD: We evaluated the frequency of anxiety disorders and depressive disorders in 271 subjects presenting with a diagnosis of either anorexia nervosa or bulimia, using the Mini International Neuropsychiatric Interview (MINI), DSM IV version. We compared the prevalences between sub-groups of anorexics (AN-R and AN-BN), between sub-groups of bulimics (BN-P and BN-NP) and between anorexics and bulimics while adjusting for the variables defined below. RESULTS: Current or lifetime comorbidity of anxiety and depressive disorders did not differ between AN-Rs and AN-BNs, nor between BN-Ps and BN-NPs. Only current diagnoses of agoraphobia and obsessive-compulsive disorder were significantly more frequent in anorexics than in bulimics. CONCLUSION: The greater frequency of comorbidity between obsessive-compulsive disorder and AN compared to BN, already well documented, is not questioned. The remaining anxiety disorders are equally frequent among all the diagnostic types of ED.

Mood disorders in eating disorder patients: Prevalence and chronology of ONSET.

OBJECTIVES: In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control group matched for age and gender. METHOD: The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. RESULTS: Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. LIMITATIONS: Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. CONCLUSION: Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders.

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.

Factorial structure of the 20-item Toronto Alexithymia Scale: confirmatory factorial analyses in nonclinical and clinical samples.

OBJECTIVE: The 20-item Toronto Alexithymia Scale (TAS-20) measures three intercorrelated dimensions of alexithymia: (1) difficulties identifying feelings (DIF), (2) difficulties describing feelings (DDF), and (3) externally oriented thinking (EOT). The aim of the study was to test the three-factor model of the TAS-20 using confirmatory factorial analyses (CFA). METHOD: 769 healthy subjects and 659 patients meeting the DSM-IV criteria for substance use disorders or eating disorders completed the TAS-20. The correlation matrices for each of the samples were analyzed with LISREL 7.16. RESULTS: In each sample, the three-factor model was found to be replicable. CONCLUSION: The three TAS-20 subcales can be used to explore the distinct facets of the alexithymia construct.

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.

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.

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.

[Undesirable effects of drugs. Epidemiologic study at a psychiatric service of a university hospital]. / Effets indesirables medicamenteux. Etude epidemiologique dans un service de psychiatrie hospitalo-universitaire.

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).

[Yawning and sexual excitation under clomipramine. Role of serotoninergic mechanisms. Apropos of 2 cases]. / Bâillements et excitation sexuelle sous clomipramine. Place des mécanismes sérotoninergiques. A propos de deux cas.

We report two cases of a singular side effect induced by clomipramine, one in a man, the other in a woman (both patients were beninese). This consisted of the occurring of the association of very frequent yawning and sexual excitation (sexual excitation with vaginal lubrification for the woman and hypogastric feeling of sexual pleasure for the man). It appeared after a few days of ambulatory treatment of a depression with clomipramine 75 mg/day. Clomipramine and demethylclomipramine blood levels were respectively 85 and 95 ng/ml and 70 and 80 ng/ml for the two patients. Three similar cases had been reported in the literature with this same tricyclic antidepressant. Recently a first case has been reported with fluoxetin. On this basis, it could be suggested that serotoninergic mechanisms are involved in the development of such clinical manifestations. But it seems reasonable to consider that serotoninergic mechanism could interact with a dopaminergic one. In favour of this hypothesis is the implication of dopaminergic mechanisms in yawning in man or in the association yawning--penile erections in the rat. Some others clinical arguments are discussed.

[Prediction of suicide risk]. / Prédiction du risque suicidaire.

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.

[Clinical tolerance of a new antidepressant -- milnacipran]. / Tolérance clinique d'un nouvel antidépresseur, le milnacipran.

Milnacipran is a new antidepressant which has been developed for its selective inhibition of both serotonin and noradrenaline reuptake with a good safety and tolerability profile. The efficacy and tolerance profile of this antidepressant have been compared with those of tricyclic and selective serotonin reuptake inhibitor antidepressants (SSRIs) in open-label and placebo-controlled trials. But no data in clinical practice are available. The authors studied the tolerability of milnacipran (100 to 200 mg/d) in 28 depressed inpatients receiving usual comedications during a mean period of 33 days (3 to 107 days). The incidence of adverse events was determined with the help of the Pharmacovigilance Center of the Centre Hospitalo-Universitaire (Besançon, France). Among the 28 patients, milnacipran was well tolerated by 18 of them. Side-effects were noted in 10 patients, but they led to withdrawal of the antidepressant in only 2 cases, where dyspnea, palpitations, pollakiuria in a case and headache, nausea, dysuria in the other case occurred. The most frequent adverse event observed was hypotension (n = 6), but in each case it occurred just after the addition of sedative phenothiazines (n = 5) or of a comedication with phenothiazines and valpromide (n = 1). So this side-effect could not be attributed to milnacipran alone. Treatments with heptaminol or theodrenaline and cafedrine were useful. An increase of the cardiac frequency seemed to occur with milnacipran (p < 0.06). It was observed in the 5 inpatients for whom this cardiovascular parameter was recorded before and during the milnacipran treatment. In 5 other patients, the cardiac frequency seemed to decrease when milnacipran was stopped for lack of good efficacy or adverse events. Gastrointestinal disturbances were scarce isolated (nausea n = 1), but necessitated a treatment with metopimazine. The milnacipran prescription (100 mg/d) after an other antidepressant treatment had been done without a withdrawal period and without problem, even when the previous antidepressant was a SSRIs with a long half-life and CYP450 inhibitory properties. The authors concluded to the good tolerability of milnacipran in usual clinical practice.

[Abuse of tianeptine. A case report]. / Abus de tianeptine. A propos d'un cas.

The authors report a case of tianeptine abuse in a 30 year-old woman. After a medical prescription of the recommended dosage of 12.5 mg 3 times daily of oral tianeptine for a depressive illness, the patient spontaneously increased the dosage which after two months reached 150 tablets per day. No severe toxic effects were observed. As adverse effects, the patient, in the beginning of this high treatment period suffered from nausea, vomiting, abdominal pain, anorexia with weight loss, constipation. These side effects progressively disappeared. The biological tolerance was excellent, and hepatic parameters were not affected. The patient experienced and seek a psychostimulant effect. After seven months of such a therapy, she was hospitalized to undergo a withdrawal. The discontinuation of the tianeptine treatment occurs in four days. A withdrawal syndrome marked by myalgia, and cold feeling was transient, and alleviated by sedative phenothiazine (cyamemazine) and myorelaxant benzodiazepine (tetrazepam).

[Consumption of benzodiazepines in a university hospital center]. / Consommation de benzodiazépines dans un centre hospitalo-universitaire.

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.

[Amineptin dependence. Detection of patients at risk. Report of 8 cases]. / Dépendance à l'amineptine. Détection de sujets à risques. A propos de huit cas.

The authors relate eight cases of amineptine dependency collected between 1980 and 1988 in 7 women and 1 man treated in the CHU of Besançon (France). The pharmacodependency appeared to be limited mainly to an abuse and a psychic dependence, i.e. a compulsive need to use the drug on a periodic (two cases) or continuing (six cases) basis in order to experience its psychomotor stimulant like effect. The used dosages ranged between 1,000 and 2,500 mg per day. The daily dose was divided into little doses, every hour for example. The induction modality was progressive during weeks or months and a stable dose period was then encountered. In one patient only, we observed a progressive increase of the dose without stabilisation of the dose. The withdrawal of amineptine was obtained without problem except in 2 cases where we observed clinical manifestations of anxiety, psychomotor agitation or bulimia during one day. Four years after the beginning, amineptine dependence was still present in 2 patients. In 4 patients we obtained an interruption of the amineptine pharmacodependency for one to three years. We did not see again the two remaining patients. In two cases, the main diagnosis, according to DSM III, was a major personality disorder (borderline). In the six other cases the diagnosis was a bipolar affective disorder (including four cases with only hypomanic episodes only). In these six patients the main characteristic of their affective illness was the association with other psychiatric disorders, especially personality disorders, such as borderline personality in one case and atypical personality with uncontrolled behavior as the main feature, in the 5 other patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thyroid function in depressed patients]. / Etude de la fonction thyroïdiene chez les déprimés.

This preliminary report compares the FT3, FT4, TSH basal levels and FT4/FT3 ration of depressed patients (DSM III-R criteria) with those of a healthy control group. Authors have also studied thyroid parameters in function of some clinical depression data (polarity, intensity and endogenous character) and other factors as age and sex. 81 depressed patients (31 men, 50 women), with mean age of 44.85 years were studied. 44 patients suffered of an endogenous depression and 37 of a non endogenous depression (Newcastle criteria). 60 patients had an unipolar depression while 21 patients had a bipolar depression. The control group was constituted of 36 healthy subjects (20 men, 16 women), with mean age of 40.94 years. There is no significant difference between the two groups for sex and age, besides the different size of the two groups. FT3 mean of depressed patients was 4.39 pmol/l. There was a significant difference between unipolar group FT3 mean (4.51 +/- 1.01 pmol/l) and bipolar FT3 mean (4.03 +/- 0.91 pmol/l; t = 2.02, p < 0.05). Depression intensity was correlated negatively to FT3 mean (r = -0.23; t = 2.10, p < 0.005). FT4 mean in the depressed group was 12.62 +/- 4.14 pmol/l. The only significative result for FT4 was its correlation to TSH levels (r = -0.36; t = 3.43, p < 0.001). TSH mean in depressed patients was 1.43 +/- 0.85 microIU/ml. When we have compared these results with those of control group we concluded that FT3 and TSH levels were significantly lower in the depressed group (FT3: t = 4.83, p < 0.0001; TSH; t = 2.44 p < 0.02) and that FT4 was slightly but not significantly increased in the depressed group. FT3 decrease and the slight FT4 increase in depression may be the consequence of a metabolic deviation of FT4 transformation into FT3. Its link with intensity and polarity of depression suggests that it can be considered as a biological marker of this disease.

[Indications for electroconvulsive therapy]. / La place de l'électroconvulsivothérapie.

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.

[Extrapyramidal side effects of neuroleptic and antidepressant treatment: assessment of potential risk factors through CYP2D6 genetic polymorphism]. / Effets indésirables extrapyramidaux des neuroleptiques et antidépresseurs--recherche de facteurs de risque: rôle du polymorphisme génétique du CYP2D6.

The objective of this study was to assign metabolizer phenotype (cytochrome P450 2D6 or CYP2D6) to drug treated psychiatric adult patients to assess if the CYP2D6 polymorphism could be a potential risk factor for the development of extrapyramidal side effects of psychotropic drugs. Twenty-eight unrelated in-patients (16 men and 12 women) treated with antidepressants and/or antipsychotic drug were phenotyped using dextromethorphan. Two groups of patients were considered depending on the presence (n = 14) or not (n = 14) of extrapyramidal side effects. The mean dextromethorphan/dextrorphan metabolic ratio (log10) did not differ between the two groups of patients (-1.13 +/- 0.9 and -1.56 +/- 0.5, NS). But significantly more patients with extrapyramidal side effects (n = 4) than patients without side effects (n = 0) were poor metabolizers. This result could be due to a quantitative difference between the 2 groups of drug treatment cosegregated with dextromethorphan, but several authors reported that extrapyramidal side effects seemed not to be always related to high plasma drug levels. So the authors concluded that the 2D6 polymorphism could be a risk factor of poor neurologic tolerance of psychotropic drugs, but not only through pharmacokinetic consequences. CYP 2D6 is indeed expressed in brain and seems to interfer with the metabolism of dopamine and other related neurotransmitters.

[Fluoxetine and tricyclic antidepressants: clinical tolerance in short-term combined administration]. / Fluoxétine et antidépresseurs tricycliques: tolérance clinique à court terme de l'association.

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.

[Grapefruit juice as a contraindication? An approach in psychiatry]. / Faut-il contre-indiquer le jus de pamplemousse? Une approche en psychiatrie.

The authors investigated in this preliminary study the influence of grapefruit juice on the metabolism of two tricyclic antidepressants. An increase of plasma concentrations is observed indeed for many drugs when administered concomitantly with grapefruit juice. This effect was mainly attributed to inhibition of cytochrome P450 1A2 and 3A4 enzymes by naringenin. These isoenzymes are involved too in the metabolism of many psychotropic drugs. Only two benzodiazepines (midazolam and triazolam) were studied in the conditions of grapefruit juice association. All these studies are performed in healthy subjects and with a study design very different from the clinical conditions. On the basis of these considerations, the authors hypothesized that grapefruit juice should inhibit tricyclic antidepressant metabolism and thus increase the bioavailability of these drugs. They want to precise if this possible drug plasma level increase could be clinically important for depressed patients. Fourteen depressed inpatients were selected for the study. Seven of them received amitriptyline (100 to 150 mg/d) and the seven others clomipramine (112.5 to 225 mg/d). Tricyclic antidepressant and desmethylated metabolite plasma levels were determined on four occasions. The first and second day samples were obtained to determined the plasma level intraindividual variability of antidepressants. On the third and fourth days, plasma levels were determined after an oral coadministration of the antidepressant and 250 ml of pure and fresh grapefruit juice. One patient was excluded from the study due to the coadministration of clomipramine and fluvoxamine. There is indeed a major drug-interaction between these two drugs, and the tricyclic antidepressant plasma levels of this patient were in the toxic range, without side effect. In this group of patients, there was no metabolic interaction between amitriptyline and grapefruit juice. But the mean plasma levels of clomipramine and desmethylclomipramine increased after coadministration of this juice (+4.5% and +10.5% respectively). The authors concluded that with these preliminary results, the potential clinical relevance of this interaction cannot be estimated.