RESUMEN
OBJECTIVE: The authors compared the effectiveness of fluoxetine and desipramine treatment in a prospective double-blind pharmacogenetics study in first-generation Mexican Americans and examined the role of whole-exome functional gene variations in the patients' antidepressant response. METHOD: A total of 232 Mexican Americans who met DSM-IV criteria for major depressive disorder were randomly assigned to receive 8 weeks of double-blind treatment with desipramine (50-200 mg/day) or fluoxetine (10-40 mg/day) after a 1-week placebo lead-in period. Outcome measures included the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale, and the Beck Depression Inventory. At week 8, whole-exome genotyping data were obtained for 36 participants who remitted and 29 who did not respond to treatment. RESULTS: Compared with desipramine treatment, fluoxetine treatment was associated with a greater reduction in HAM-D score, higher response and remission rates, shorter time to response and remission, and lower incidences of anticholinergic and cardiovascular side effects. Pharmacogenetics analysis showed that exm-rs1321744 achieved exome-wide significance for treatment remission. This variant is located in a brain methylated DNA immunoprecipitation sequencing site, which suggests that it may be involved in epigenetic regulation of neuronal gene expression. This and two other common gene variants provided a highly accurate cross-validated predictive model for treatment remission of major depression (receiver operating characteristic integral=0.95). CONCLUSIONS: Compared with desipramine, fluoxetine treatment showed a more rapid reduction of HAM-D score and a lower incidence of side effects in a population comprising primarily first-generation Mexican Americans with major depression. This study's pharmacogenetics approach strongly implicates the role of functional variants in antidepressant treatment response.
Asunto(s)
Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/genética , Trastorno Depresivo Mayor/tratamiento farmacológico , Desipramina/uso terapéutico , Fluoxetina/uso terapéutico , Americanos Mexicanos , Polimorfismo de Nucleótido Simple , Inhibidores de Captación Adrenérgica/uso terapéutico , Adulto , Anciano , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Antidepresivos de Segunda Generación/uso terapéutico , Antidepresivos Tricíclicos/uso terapéutico , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/psicología , Desipramina/administración & dosificación , Desipramina/efectos adversos , Método Doble Ciego , Esquema de Medicación , Epigénesis Genética , Femenino , Fluoxetina/administración & dosificación , Fluoxetina/efectos adversos , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Farmacogenética , Valor Predictivo de las Pruebas , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Proyectos de Investigación , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Resultado del TratamientoAsunto(s)
Citocromo P-450 CYP2D6/genética , Depresión/tratamiento farmacológico , Desipramina/efectos adversos , Fluoxetina/efectos adversos , Americanos Mexicanos/genética , Adulto , Depresión/etnología , Desipramina/administración & dosificación , Método Doble Ciego , Fluoxetina/administración & dosificación , Humanos , Hipotensión Ortostática/inducido químicamente , Persona de Mediana Edad , Polimorfismo Genético , Estudios Prospectivos , Taquicardia/inducido químicamente , Trastornos de la Visión/inducido químicamenteRESUMEN
Body weight change was monitored in 73 hospitalized depressed patients treated with one of four antidepressants for 1 month. After a 2-week medication-free period, patients were randomly assigned to treatment with amitriptyline, nortriptyline, desipramine, or zimelidine. By the end of 1 month, treatment with all three tricyclic compounds promoted weight gain, with the greatest increase observed during amitriptyline treatment; less weight was gained by patients treated with nortriptyline and desipramine. In contrast, most patients treated with zimelidine showed no weight gain and, in many cases, demonstrated weight loss. Weight change during treatment was not associated with age, sex, severity of depression, obesity, weight loss during depression, or clinical response.
Asunto(s)
Antidepresivos/efectos adversos , Trastorno Depresivo/tratamiento farmacológico , Aumento de Peso/efectos de los fármacos , Adulto , Amitriptilina/efectos adversos , Antidepresivos/uso terapéutico , Desipramina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nortriptilina/efectos adversos , Zimeldina/efectos adversosAsunto(s)
Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Sistema Cardiovascular/efectos de los fármacos , Desipramina/uso terapéutico , Adolescente , Presión Sanguínea/efectos de los fármacos , Niño , Desipramina/efectos adversos , Desipramina/sangre , Electrocardiografía , Sistema de Conducción Cardíaco/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Factores de TiempoRESUMEN
The results of a double blind trial of Viloxazine and Desipramine in 30 hospitalized depressives are reported. Hamilton's Rating Scale for Depression was the outcome criterion. No statistically significant differences were found between drugs in efficacy and onset of action. Patients on either drug showed a significant reduction in symptoms after one week of treatment and at the end of the trial. Side effects reported with Viloxazine were predominantly nausea and dizziness of a transient nature. Patients on Desipramine reported the usual side effects associated with antidepressant use and two of them had to be withdrawn from the trial because of an allergic rash. Laboratory values and EKG tracings did not show any trend of abnormalities. It is concluded that Viloxazine is an effective and safe antidepressive drug and seems to be particularly indicated in geriatric and cardiovascular patients with a concomitant depression.