RESUMO
BACKGROUND: Cerebrovascular disease may cause "vascular depression" (VaD). Calcium channel-blockers are presumed treatments for cerebrovascular disease and might be expected to improve depression and prevent recurrence. OBJECTIVE: To examine the efficacy and tolerability of the use of nimodipine as an augmentation of fluoxetine in the treatment of VaD. DESIGN: A double-blind, randomized clinical trial in which 101 patients with VaD (Alexopoulos criteria) were treated with fluoxetine at standard doses. Patients were randomized to placebo (n=51) or nimodipine (n=50). Treatment outcomes were assessed using the Hamilton Depression Rating Scale (HDRS) regularly up to 8 months after treatment initiation. RESULTS: Depression was reduced in 63% of patients, but those whose treatment was enhanced with nimodipine had greater improvements overall by repeated measures analysis of covariance (ANCOVA) (F(1.80) = 9.76, p=0.001). In addition, a greater proportion of patients treated with fluoxetine-nimodipine (54% vs. 27%) exhibited full remission (chi2(d.f. 1)= 7.3, p = 0.006), with the number needed to treat (NNT) equal to 4 (95% CI 2-12). Of those experiencing full remission in the first 61 days, fewer patients on fluoxetine-nimodipine (3.7%) developed recurrence of major depression as compared to those on fluoxetine alone (35.7%) (chi2(d.f. 1) = 7.56, p = 0.006), NNT 3 (95% CI 2-9). Side-effects were noted in 33.3% of patients in the control group and 48% of the experimental group (chi2(d.f. 1) = 2.25, p = 0.133). CONCLUSIONS: In treating VaD, augmentation of fluoxetine with nimodipine led to better treatment results and lower rates of recurrence. These findings support the argument that augmentation of antidepressant therapy might be helpful in the treatment of cerebrovascular disease, which is involved in the pathogenesis of this type of depression.
Assuntos
Antidepressivos de Segunda Geração/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Transtornos Cerebrovasculares/complicações , Transtorno Depressivo/tratamento farmacológico , Fluoxetina/administração & dosagem , Nimodipina/administração & dosagem , Idoso , Argentina , Transtornos Cerebrovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/psicologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prevenção SecundáriaRESUMO
BACKGROUND: 'Vascular depression' may be caused by cerebrovascular disease. Calcium channel blockers, which are putative treatments for cerebrovascular disease, might be expected to improve depression reduction and to prevent recurrence of depression in this patient population. This clinical trial was designed to test these hypotheses. DESIGN: This was a controlled, double blind, randomized clinical trial in which 84 patients with vascular depression (Alexopoulos criteria) were treated with antidepressants at standard doses. Patients were also randomized to nimodipine (n = 40) or an inactive comparator, vitamin C (n = 44). Treatment outcomes were assessed using the Hamilton depression rating scale (HDRS) regularly up to 300 days after treatment initiation. RESULTS: As expected, depression reduction was successful in most patients. In addition, those treated with nimodipine plus an antidepressant had greater improvements in depression overall in repeated measures ANCOVA (F(1,81) = 8.64, p = 0.004). As well a greater proportion of nimodipine-treated participants (45 versus 25%) exhibited a full remission (HDRS < or = 10) (chi(2)(df, 1) = 3.71, p = 0.054). Among those experiencing a substantial response in the first 60 days (50% reduction in HDRS), fewer patients on nimodipine (7.4%) had a recurrence of major depression when compared to those on antidepressant alone (32%) (chi(2)(df, 1) = 3.59, p = 0.058). CONCLUSIONS: In treating vascular depression, augmentation of antidepressant therapy with a calcium-channel blocker leads to greater depression reduction and lower rates of recurrence. These findings support the argument that cerebrovascular disease is involved in the pathogenesis and recurrence of depression in these patients.