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 (χ2(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%) (χ2(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 (χ2(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.