Pharmacokinetics and dosing requirements of digoxin in pregnant women treated for fetal supraventricular tachycardia.

BACKGROUND: The objective of this study was to characterize the pharmacokinetics (PK) of digoxin in pregnant women and its potential implications for drug dosing. METHODS: Serum digoxin concentrations (SDCs) obtained in pregnant women treated for fetal supraventricular tachycardia (SVT) was retrospectively collected. PK analysis was comparatively performed using a two-stage approach (PKS™) and a Population PK approach (NONMEM™). As clinical outcome the fetal heart rate was recorded. RESULTS: A total of 42 SDCs were obtained from 8 women in the 3rd trimester of pregnancy (mean age 33.0 years). The PK parameters estimated by both two-stage (volume of distribution (Vd) = 682.0 L, CV = 47.5%; serum clearance (CL) = 16.1 L/h, CV = 19%) and population approaches (Vd = 731.3 L, CV = 30.5%; CL = 18.7 L/h, CV = 17.8%) are very similar and show a clear trend of increasing drug disposition in the third trimester of pregnancy. An oral loading dose of 0.5 mg/8 h during 24 h followed by a maintenance regimen of 0.5 mg/12 h been recommended to start treatment. CONCLUSIONS: Despite the small population, these parameters could be used as a guide to calculate the initial dosage requirements in the third trimester of pregnancy for treating fetal SVT. In addition, maternal SDCs should be routinely monitored for dosage adjustment purposes.

Trastorno esquizofreniforme. Estudio prospectivo de 5 años de seguimiento / Schizophreniform disorder. A 5-year prospective follow-up study

Introducción: Estudio prospectivo de 5 años, cuyo objetivo es evaluar la estabilidad temporal del diagnóstico de trastorno esquizofreniforme (TE) provisional y evaluar la validez predictiva de las características de buen pronóstico que define el Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-IV). Sujetos y métodos: La muestra consta de 38 pacientes (23 varones y 15 mujeres) ingresados en el hospital, entre 1996 y 1998, por un primer episodio psicótico. Se realizaron 4 entrevistas de seguimiento: en el primer, segundo, tercer y quinto años. Los pacientes se evaluaron mediante la Brief Psychiatric Rating Scale (BPRS), la Escala de Evolución de Strauss-Carpenter, la entrevista clínica estructurada del DSM-IV (SCID) y la Escala de Evaluación de la Actividad Global (EEAG). Resultados: Completaron el seguimiento de 5 años 27 pacientes. El 25,9% mantenía el diagnóstico de TE a los 5 años y el 59,2% se clasificaron dentro del espectro esquizofrénico. La presencia en el primer ingreso de características de buen pronóstico se asoció con una mejor evolución a los 5 años, pero no se asoció al mantenimiento del diagnóstico de TE. Los pacientes que mantuvieron el diagnóstico de TE presentaron mejor evolución que los pacientes esquizofrénicos. Conclusiones: Tras 5 años de seguimiento, la mayoría de los pacientes continúan presentando síntomas y cumplen criterios de esquizofrenia o trastorno esquizoafectivo, lo que confirma la baja estabilidad del diagnóstico TE. Los hallazgos sugieren una asociación entre las características de buen pronóstico y una mejor evolución, aunque no se observa asociación con el mantenimiento del diagnóstico TE

Introduction: We performed a 5-year prospective study to evaluate the temporal stability of a provisional diagnosis of schizophreniform disorder (SFD) and evaluate the predictive value of the good prognostic features defined in the DSM-IV. Subjects and Methods: The sample consisted of 38 patients (23 men and 15 women) admitted to our hospital from 1996 to 1998 for a first psychotic episode. Four follow-up interviews were obtained: at the first, second, third and fifth years of follow-up. Patients were evaluated by means of the Brief Psychiatric Rating Scale (BPRS), the Strauss-Carpenter Scale, the Structured Clinical Interview of the DSM-IV (SCID) and the Global Assessment of Functioning Scale (GAF Scale) of the DSM-IV. Results: Twenty-seven patients completed the study. A total of 25.9% retained the diagnosis of SFD and 59.2% were classified as having a disorder of the schizophrenic spectrum. The presence of good prognostic features at the index admission was associated with better outcome, but not with maintenance of the diagnosis of SFD. After 5 years of follow-up, patients with SFD showed significantly better outcomes than did schizophrenic patients. Conclusions: After 5 years of follow-up most of the patients continued to have symptoms and met the criteria for schizophrenia or schizoaffective disorder, confirming the low stability of a provisional diagnosis of SFD. The results of this study suggest an association between good prognostic features and better outcome, but not with maintenance of a diagnosis of SFD

[Validation study of the Center for Epidemiological Studies-Depression of a Spanish population of patients with affective disorders]. / Estudio de validación del Center for Epidemiologic Studies-Depresion (CES-D) en una población española de pacientes con trastornos afectivos.

The Center for Epidemiologic Studies-Depression (CES-D) is a short self-rating scale composed of 20 items, designed to detect depressive symptomatology. It has demonstrated its sensibility in psychiatric patients and general population. The CES-D was administered to 99 patients, 33 men and 66 women with mean age of 44.14 years. The patients had been diagnosed of: Major Depressive Disorder (74%), Bipolar Disorder (10%), Adaptive Disorder with depressive mood (10%) and other mood disorders (6%) according to DSM-IIIR criteria. In order to study the validity and reliability of the CES-D, we administered the Hamilton Rating Depression Scale, the Beck Depression Inventory and analogical scales to all the patients. In the reliability analysis we obtain 0.9 alpha. The factor analysis show 4 factors who explain the 58.8% of the variance: "depresses Affect/Somatic", "Positive Affect", "Irritability/Hopelessness", "Interpersonal/Social". The scale shows a 0.95 sensibility and 0.91 specificity to depressive symptomatology detection (according to scores equal or over 9 on HRSD) taking as cutoff scores equal or over 16 on CES-D. Our results show that the CES-D is a sensitive and specify tool for depressive symptomatology detection in psychiatric population. The CES-D is easy to be completed and evaluated, therefore may be useful in epidemiologic studies in general populations.

Predicting outcome of lithium added to antidepressants in resistant depression.

This study was conducted to assess the predictive value of different variables including the response to dexamethasone suppression test (DST), in 105 patients with resistant depression after the addition of lithium (600 to 800 mg/day) for 4 weeks to antidepressant medication. Clinical remission was observed in 57 patients and no improvement in 48. A dramatic and rapid relief of depression occurred in 12 patients. Variables with significant or marginally significant differences between responders and non-responders were included in a stepwise logistic regression model. Weight loss (P = 0.0013) and depressive psychomotor activity (P = 0.045) in the Newcastle diagnostic index (NDI) scale, and overall score of the Hamilton Rating Scale for Depression (HRSD) before adding the lithium (P = 0.0039) were significantly associated with clinical remission. The difference in post-DST cortisol plasma levels between both groups was marginally significant. The logistic equation resulted in a sensitivity of 78% and a specificity of 65% and total correct classification of the lithium-added response of 72%. The clinical profile of patients who improve with the addition of lithium may include significant weight loss, psychomotor retardation and possibly, poor control of cortisol secretion. Partial remission before adding lithium as well as endogenomorphic traits according to NDI may also be considered additional criteria for response.

Ten years' experience with clozapine in treatment-resistant schizophrenic patients: Factors indicating the therapeutic response.

A prospective study in treatment-resistant schizophrenic patients was performed over 10 years to evaluate the therapeutic response to clozapine and the variables related to this treatment. Eighty schizophrenic and schizoaffective patients (according to Diagnostic and Statistical Manual [DSM]-IIIR criteria), considered as refractory (previously resistant to at least two different typical neuroleptics), were studied. The average dose of clozapine was 267 mg/d. The clinical variables considered were: Brief Psychiatric Rating Scale (BPRS), number of admissions before and after clozapine treatment and the Strauss-Carpenter scale as measures of efficacy; Premorbid Adjustment Scale (PAS), to assess personal and social adjustment before illness; Karolinska Personality Scale (KPS) to assess stable traits of personality; and the Simpson-Angus scale as a measure of extrapyramidal symptoms. Sixty percent of patients showed a significant improvement after clozapine treatment. Side-effects were mild and well tolerated, with no cases of haematological disturbance and only five withdrawals because of adverse events. The severity of the episode, according to BPRS score and anxiety as a personal trait, are related to good prognosis. Other relationships between improvement and clinical and demographic variables are discussed.

[Plasmatic concentrations of fluoxetine, pharmacokinetics, therapeutic response and side effects]. / Niveles plasmáticos de fluoxetina: farmacocinética, respuesta terapeútica y efectos secundarios.

The kinetics of fluoxetine and possible relations between the drug's plasmatic concentration and therapeutic response and side effects were evaluated in a sample of 66 depressive patients, 26 men and 40 women, average age 46.6 years (SD = 14.1), diagnosed according to DSM-III criteria and evaluated using the Hamilton scale for depression (17-item HRSD). We found no difference between plasmatic concentration of fluoxetine in weeks 3 and 6 of treatment, nor in the sum of drug plus active principle in weeks 3 and 6. There was no significant linear correlation between plasmatic concentrations of fluoxetine, norfluoxetine, or the sum of both in weeks 3 and 6 and score on the Hamilton scale in week 6. By means of serial Chi-score calculation we found a "minimum plasmatic concentration" of about 30 ng/ml below which there was less therapeutic response.