RESUMO
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.
Assuntos
Antidepressivos/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/genética , Transtorno Depressivo Maior/tratamento farmacológico , Desipramina/uso terapêutico , Fluoxetina/uso terapêutico , Americanos Mexicanos , Polimorfismo de Nucleotídeo Único , Inibidores da Captação Adrenérgica/uso terapêutico , Adulto , Idoso , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Antidepressivos de Segunda Geração/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Desipramina/administração & dosagem , Desipramina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Epigênese Genética , Feminino , Fluoxetina/administração & dosagem , Fluoxetina/efeitos adversos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Valor Preditivo dos Testes , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Projetos de Pesquisa , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Resultado do TratamentoAssuntos
Citocromo P-450 CYP2D6/genética , Depressão/tratamento farmacológico , Desipramina/efeitos adversos , Fluoxetina/efeitos adversos , Americanos Mexicanos/genética , Adulto , Depressão/etnologia , Desipramina/administração & dosagem , Método Duplo-Cego , Fluoxetina/administração & dosagem , Humanos , Hipotensão Ortostática/induzido quimicamente , Pessoa de Meia-Idade , Polimorfismo Genético , Estudos Prospectivos , Taquicardia/induzido quimicamente , Transtornos da Visão/induzido quimicamenteRESUMO
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.
Assuntos
Antidepressivos/efeitos adversos , Transtorno Depressivo/tratamento farmacológico , Aumento de Peso/efeitos dos fármacos , Adulto , Amitriptilina/efeitos adversos , Antidepressivos/uso terapêutico , Desipramina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nortriptilina/efeitos adversos , Zimeldina/efeitos adversosAssuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Sistema Cardiovascular/efeitos dos fármacos , Desipramina/uso terapêutico , Adolescente , Pressão Sanguínea/efeitos dos fármacos , Criança , Desipramina/efeitos adversos , Desipramina/sangue , Eletrocardiografia , Sistema de Condução Cardíaco/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Fatores de TempoRESUMO
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.