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1.
Gynecol Obstet Fertil ; 32(11): 954-60, 2004 Nov.
Artículo en Francés | MEDLINE | ID: mdl-15567684

RESUMEN

OBJECTIVE: Evaluate the compliance to the national guidelines from ANDEM (1996) and AFSSAPS (2003) concerning the diagnosis of infertility, the prescription of clomiphene and the monitoring of these treatments. PATIENTS AND METHODS: Retrospective study of female patients from 16 to 50 y.o. having benefited from reimbursement of clomiphene citrate treatment between 1st April 2002 and 30th June 2002. After random sampling stratified on age, data on diagnosis procedures and treatments were extracted from the Social Security reimbursement database. These data were validated and completed by patients' interviews. RESULTS: A total of 283 women were included. 30% were subject to the basic hormonal tests (FSH, LH, estradiol). The proportion of patients explored by hysterosalpingogram, post-coital test and echography were respectively 50%, 35% and 68%. A semen analysis was found in 60% of the partners. The complete set of recommended tests before start of treatment was realised in 1.5% of women. In 7% of cases, women were treated without prior exploration. The proportion of tests performed was comparable below and above the age of 35. 77% of treatments were initiated after at least one year of waiting for a spontaneous conception. 69% of women were monitored during treatment by other methods than clinical follow-up. CONCLUSION: Prescription of clomifene citrate is too frequently realised without compliance to guidelines applicable to infertility investigations and therefore without persuasive diagnosis. These practices can lead to loss of childbearing opportunities and complications.


Asunto(s)
Atención Ambulatoria/normas , Clomifeno/administración & dosificación , Infertilidad Femenina/diagnóstico , Infertilidad Femenina/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Adulto , Femenino , Francia , Humanos , Masculino , Embarazo , Semen/fisiología
2.
J Clin Psychopharmacol ; 16(4): 307-14, 1996 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-8835706

RESUMEN

Sixty-nine depressive patients (DSM III criteria: 296.2, 296.3, 296.5, 300.4) were treated with 40 to 60 mg citalopram (CIT) daily for 4 weeks. Among them, 45 responded to treatment (improvement > 50% on the 21-item Hamilton Rating Scale for Depression [HAM-D]) and continued their treatment for another week before being released from the study. The 24 nonresponders were randomized and comedicated under double-blind conditions with lithium carbonate (Li) (2 x 400 mg/day) (CIT-Li group) or with placebo (CIT-Pl group) from days 29 to 35. For days 36 to 42, the patients of both subgroups were treated openly with Li (800 mg/day) in addition to the ongoing CIT treatment. On day 35, 6 of 10 patients responded to the CIT-Li combination, whereas 2 of 14 patients only responded to the CIT-Pl combination. This group difference reached significance (p < 0.05) on day 35 with lower HAM-D total scores in the CIT-Li group. No evidence was seen of a pharmacokinetic interaction between CIT and Li, and this combination was well tolerated. Patients were phenotyped with dextromethorphan and mephenytoin at baseline and at day 28. As evaluated at baseline, three patients (responders) were poor metabolizers of dextromethorphan and six patients (three responders and three nonresponders) of mephenytoin. On day 28, the ratio CIT/N-desmethylCIT (DCIT) in plasma was significantly higher in poor than in extensive metabolizers of mephenytoin (p = 0.0001), and there was a significant positive correlation between the metabolic ratio of dextromethorphan and the ratio DCIT/N-didesmethylCIT in plasma (p < 0.001). These findings illustrate the role of CYP2D6 and CYP2C19 in the metabolism of CIT. It can be concluded that Li addition to CIT is effective in patients not responding to CIT alone without any evidence of an accentuation or provocation of adverse events.


Asunto(s)
Antidepresivos/administración & dosificación , Hidrocarburo de Aril Hidroxilasas , Citalopram/administración & dosificación , Citalopram/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Carbonato de Litio/administración & dosificación , Oxigenasas de Función Mixta/metabolismo , Inhibidores de la Captación de Serotonina/administración & dosificación , Adulto , Citalopram/sangre , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2D6/genética , Sistema Enzimático del Citocromo P-450/genética , Trastorno Depresivo/genética , Dextrometorfano/metabolismo , Método Doble Ciego , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Humanos , Masculino , Mefenitoína/metabolismo , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética
3.
J Chromatogr ; 616(2): 221-8, 1993 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-8376503

RESUMEN

Sensitive and specific methods based on gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) for the determination of levels of citalopram, desmethylcitalopram and didesmethylcitalopram in the plasma of patients treated with citalopram are presented, as well as a GC-MS procedure for the assay of the citalopram propionic acid derivative. After addition of a separate internal standard for each drug, liquid-solvent extraction is used to separate the basic compounds from the acid compounds. The demethylated amines are derivatized with trifluoroacetic anhydride, and the acid metabolite with methyl iodide. GC-MS is performed in the electron impact mode, as mass spectrometry by the (positive-ion) chemical ionization mode (methane and ammonia) appeared to be unsuitable. The limits of quantification were 1 ng/ml for citalopram and desmethylcitalopram and 2 ng/ml for the other metabolites. The correlation coefficients for the calibration curves (range 10-500 ng/ml) were > or = 0.999 for all compounds, whether determined by GC or GC-MS.


Asunto(s)
Citalopram/sangre , Antidepresivos Tricíclicos/análisis , Cromatografía de Gases , Remoción de Radical Alquila , Desaminación , Cromatografía de Gases y Espectrometría de Masas , Humanos , Indicadores y Reactivos , Estándares de Referencia
4.
Br J Psychiatry Suppl ; (15): 66-71, 1992 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-1389025

RESUMEN

Alcohol interferes with the central metabolism of the catecholamines and especially with indolamines (5-HT). Thus, the use of an antidepressant such as tianeptine, whose main neurochemical effect is to increase the reuptake of 5-HT, seems to be particularly indicated for the continued treatment of depressed patients after alcohol withdrawal. This study evaluated the therapeutic efficacy and acceptability during long-term administration of tianeptine in depressed patients (major depressive episode or dysthymic disorder) in a multicentre trial, after withdrawal from alcohol abuse or dependence. The results relate to 130 depressed patients, who abstained from alcohol and received treatment for a year. Only one patient dropped-out because of side-effects, and medication was interrupted in 5% of subjects because of alcoholic relapses. Prescribed in the long term, tianeptine did not produce orthostatic hypotension, changes in bodyweight, or alterations in the ECG. All changes found in haematological and biochemical investigations suggested an improvement in patients' physical state. This, and other studies, indicate that tianeptine appears to have the potential to be a safe antidepressant, which might be particularly useful in those patients who are susceptible to the side-effects of psychotropic drugs.


Asunto(s)
Alcoholismo/rehabilitación , Antidepresivos Tricíclicos/administración & dosificación , Trastorno Depresivo/tratamiento farmacológico , Etanol/efectos adversos , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Tiazepinas/administración & dosificación , Adolescente , Adulto , Anciano , Alcoholismo/psicología , Antidepresivos Tricíclicos/efectos adversos , Trastorno Depresivo/psicología , Femenino , Estudios de Seguimiento , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Recurrencia , Síndrome de Abstinencia a Sustancias/psicología , Tiazepinas/efectos adversos
5.
Neuropsychobiology ; 25(4): 214-20, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1454163

RESUMEN

The pharmacokinetics and pharmacodynamics (waking EEG) of 75 mg trimipramine taken orally were determined in two healthy volunteers on two separate occasions, once without and once after comedication with 2 x 50 mg quinidine. Quinidine, a potent cytochrome P-450IID6 inhibitor, is used as a pharmacological tool to mimic a lack of this enzyme in man. In this study, it markedly altered the pharmacokinetics of trimipramine, almost doubling its plasma half-life and decreasing its apparent clearance and volume of distribution. These results strongly suggest that trimipramine is a substrate of cytochrome P-450IID6. These modifications of trimipramine metabolism were accompanied by measurable changes in some EEG variables, most notably with regard to the relative power in the alpha and theta bands, which showed higher and longer-lasting effects of trimipramine. Since cytochrome P-450IID6 is deficient in 5-10% of Caucasian subjects, this may have consequences in trimipramine-treated subjects, especially with regard to the effects of the drug on the EEG.


Asunto(s)
Nivel de Alerta/efectos de los fármacos , Electroencefalografía/efectos de los fármacos , Quinidina/farmacología , Trimipramina/farmacocinética , Administración Oral , Adulto , Corteza Cerebral/efectos de los fármacos , Potenciales Evocados/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trimipramina/administración & dosificación
6.
Ther Drug Monit ; 13(4): 356-62, 1991 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1780970

RESUMEN

The ring sulfoxidation of thioridazine (THD), a widely used neuroleptic agent, yields two diastereoisomeric pairs, fast- and slow-eluting (FE and SE) thioridazine 5-sulfoxide (THD 5-SO). Until now, studies in which concentrations of these metabolites were measured in THD-treated patients have revealed no significant differences in their concentrations. Preliminary experiments in our laboratory had shown that sunlight and, to a lesser extent, dim daylight led to racemization and probably also to photolysis of the diastereoisomeric pairs as measured by high-performance liquid chromatography. Similar results were also obtained with direct UV light (UV lamp). In appropriate light-protected conditions, THD, northioridazine, mesoridazine, sulforidazine, and FE and SE THD 5-SO were measured in 11 patients treated with various doses of THD for at least 1 week. Significantly higher concentrations of the FE stereoisomeric pair were found. The concentration ratios THD 5-SO (FE)/THD 5-SO (SE) ranged from 0.89 to 1.75 in plasma and from 1.15 to 2.05 in urine. Because it is known that the ring sulfoxide contributes to the cardiotoxicity of the drug even more potently than the parent compound does, these results justify further studies to determine whether there is stereoselectivity in the cardiotoxicity of THD 5-SO.


Asunto(s)
Luz , Tioridazina/análogos & derivados , Tioridazina/uso terapéutico , Adulto , Antidepresivos/sangre , Antidepresivos/orina , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Mesoridazina/sangre , Mesoridazina/orina , Persona de Mediana Edad , Fenotiazinas/sangre , Fenotiazinas/orina , Estereoisomerismo , Tioridazina/análisis , Tioridazina/sangre , Tioridazina/metabolismo , Tioridazina/orina
7.
Encephale ; 17(3): 213-9, 1991.
Artículo en Francés | MEDLINE | ID: mdl-1864255

RESUMEN

UNLABELLED: Citalopram, a new bicyclic antidepressant, is the most selective serotonin reuptake inhibitor. In a number of double-blind controlled studies, citalopram was compared to placebo and to known tricyclic antidepressants. These studies have shown their efficacy and good safety. The inefficacy of a psychotropic treatment in at least 20% of depressives has led a number of authors to propose original drug combinations and associations, like antidepressant/lithium (Li), antidepressant/sleep deprivation (agrypnia), antidepressant/ECT, or antidepressant/LT3. The aim of this investigation is to evaluate the clinical effectiveness and safety of a combined citalopram/lithium treatment in therapy-resistant patients, taking account of serotonergic functions, as tested by the fenfluramine/prolactin test, and of drug pharmacokinetics and pharmacogenetics of metabolism. DESIGN OF THE STUDY: A washout period of 3 days before initiating the treatment is included. After an open treatment phase of 28 days (D) with citalopram (20 mg D1-D3; 40 mg D4-D14; 40 or 60 mg D15-D28; concomitant medication allowed: chloral, chlorazepate), the nonresponding patients [less than 50% improvement in the total score on the 21 item-Hamilton Depression Rating Scale (HDRS)] are selected and treated with or without Li (randomized in double-blind conditions: citalopram/Li or citalopram/placebo) during the treatment (D29-D35). Thereafter, all patients included in the double-blind phase subsequently receive an open treatment with citalopram/Li for 7 days (D36-D42). The hypothesis of a relationship between serotoninergic functions in patients using the fenfluramine/prolactin test (D1) and the clinical response to citalopram (and Li) is assessed. Moreover, it is evaluated whether the pharmacogenetic status of the patients, as determined by the mephenytoin/dextromethorphan test (D0-D28), is related to the metabolism of fenfluramine and citalopram, and also to the clinical response. CLINICAL ASSESSMENT: Patients with a diagnosis of major depressive disorders according to DSM III are submitted to a clinical assessment of D1, D7, D14, D28, D35, D42: HDRS, CGI (clinical global impression), VAS (visual analog scales for self-rating of depression), HDRS (Hamilton depression rating scale, 21 items), UKU (side effects scale), and to clinical laboratory examens, as well as ECG, control of weight, pulse, blood pressure at D1, D28, D35. Fenfluramine/prolactin test: A butterfly needle is inserted in a forearm vein at 7 h 45 and is kept patent with liquemine. Samples for plasma prolactin, and d- and l-fenfluramine determinations are drawn at 8 h 15 (base line). Patients are given 60 mg fenfluramine (as a racemate) at 8 h 30. Kinetic points are determined at 9 h 30, 10 h 30, 11 h 30, 12 h 30, 13 h 30. Plasma levels of d- and l-fenfluramine are determined by gas chromatography and prolactin by IRNA. Mephenytoin/dextromethorphan test: Patients empty their bladders before the test; they are then given 25 mg dextropethorphan and 100 mg mephenytoin (as a racemate) at 8 h 00. They collect all urines during the following 8 hours. The metabolic ratio is determined by gas chromatography (metabolic ratio dextromethorphan/dextrorphan greater than 0.3 = PM (poor metabolizer); mephenytoin/4-OH-mephenytoin greater than 5.6, or mephenytoin S/R greater than 0.8 = PM). Citalopram plasma levels: Plasma levels of citalopram, desmethylcitalopram and didesmethylcitalopram are determined by gas chromatography--mass spectrometry. RESULTS OF THE PILOT STUDY. The investigation has been preceded by a pilot study including 14 patients, using the abovementioned protocol, except that all nonresponders were medicated with citalopram/Li on D28 to D42. The mean total score (n = 14) on the 21 item Hamilton scale was significantly reduced after the treatment, ie from 26.93 +/- 5.80 on D1 to 8.57 +/- 6.90 on D35 (p less than 0.001). A similar patCitalopram, a new bicyclic antidepressant, is the most selective serotonin reu


Asunto(s)
Citalopram/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Litio/uso terapéutico , Estudios Multicéntricos como Asunto/métodos , Adulto , Anciano , Método Doble Ciego , Quimioterapia Combinada , Humanos , Masculino , Persona de Mediana Edad
8.
Encephale ; 17(1): 37-42, 1991.
Artículo en Francés | MEDLINE | ID: mdl-1669033

RESUMEN

The clinical efficacy of a treatment with clomipramine (150 mg/day) associated with a daily dose of 50 micrograms of LT3 (CMI + LT3) compared to a treatment with clomipramine (150 mg/day) (CMI + placebo) for a period of 42 days has been examined in a pilot study, randomized in double-blind conditions, including 20 patients with a normal thyroid status, but presenting a major depressive syndrome (DSM III). The minimum including score was 30 on the Montgomery Asberg Scale (MADRS). The patients were considered as remitted when the MADRS-score was < or = 10. After 28 days of treatment, the efficacy of CMI + LT3 was found to be superior to CMI + placebo (p < 0.05). Side effects (CHESS 84) were those generally described for tricyclic antidepressants (constipation, dry mouth, lipothymia, tremor). Patients of the CMI + LT3 group experienced a slight hyperthyroidism. The determination of the plasma levels of CMI and desmethylclomipramine (DCMI) showed the presence of three non-compliant patients, but also that there was no relationship between plasma levels and clinical efficacy of the drug. Significant correlations were found between CMI and DCMI levels on day 14 compared with those of day 28 and 42, respectively. LT3 was without effect on the plasma levels of CMI and DCMI.


Asunto(s)
Clomipramina/administración & dosificación , Trastorno Depresivo/tratamiento farmacológico , Triyodotironina/administración & dosificación , Adolescente , Adulto , Clomipramina/análogos & derivados , Clomipramina/farmacocinética , Trastorno Depresivo/sangre , Trastorno Depresivo/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Pruebas de Función de la Tiroides , Hormonas Tiroideas/sangre , Triyodotironina/sangre
9.
Encephale ; 16(3): 181-7, 1990.
Artículo en Francés | MEDLINE | ID: mdl-2201514

RESUMEN

Tianeptine is a new antidepressant with a tricyclic molecular structure. Its main neurochemical effect consists in an increase in serotonine re-uptake. Its efficacy as antidepressant and its good clinical safety have been confirmed in controlled trials against reference drugs. 1,231 patients with a DSM III diagnosis of major depression or dysthymic disorder were included in a long-term trial with tianeptine. 510 patients completed the one-year treatment period. The results of a subgroup of 100 patients treated in one of the centres of south-east France will be presented. 47 of these patients completed the trial. This study allowed to evaluate the therapeutic efficacy as well as the clinical safety of tianeptine during long-term prescription. Patients were treated in an open design after a 4-7 day placebo washout period. Therapeutic effects were assessed by the C.G.I. items (1 and 2), MADRS, HARS and HSCL. For the evaluation of clinical and paraclinical safety, spontaneous complaints of the patients and CGI-3 were documented; body weight, blood pressure and blood chemistry were also measured. Homogeneity between completers and non-completers was tested before statistical analysis of the clinical effects. Results of completers were analyzed using a two-way ANOVA (time x subjects); Newman-Keuls tests were performed in the case of a significant time effect. End-point analysis was used to test the results of the total sample. Patients completing the trial had a mean MADRS baseline score of 32.8. Given high this score, the patients have to be considered genuinely depressed at inclusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Tiazepinas/uso terapéutico , Adulto , Anciano , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Recurrencia , Factores de Tiempo
10.
Encephale ; 15(6): 543-7, 1989.
Artículo en Francés | MEDLINE | ID: mdl-2612427

RESUMEN

We recently proposed the first scale for evaluating anxiety in psychotics: the "Psychotic Anxiety Scale" (PAS). The first version of this scale was tested in 45 psychotic patients. The multiple correspondence factorial analysis revealed that 4 factors account for respectively 50%, 18%, 17% and 10% of the variance. This scale thus evaluates anxiety along 4 axes: severity of the symptomatology, evolution in time, hetero-aggressiveness and self-aggressiveness. This analysis supports the hypothesis of the lack of specificity for the anxiety in psychotics, but distinguishes the nevrotic anxiety from the psychotic anxiety. The inter-rater reliability was assessed by a method which compared a rater with the others along 2 axes: the severity, and the profile of the assessment. The interrater reliability was unsatisfactory for only three items. They have been modified and a new version of the PAS is proposed.


Asunto(s)
Trastornos de Ansiedad/psicología , Escalas de Valoración Psiquiátrica/normas , Trastornos Psicóticos/psicología , Trastornos de Ansiedad/diagnóstico , Estudios de Evaluación como Asunto , Análisis Factorial , Humanos
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