A double blind, randomized clinical trial assessing the efficacy and safety of augmenting standard antidepressant therapy with nimodipine in the treatment of 'vascular depression'

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≤10) (X²(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%) (X²(df, 1)=3.59, p=0.058). Conclusion: 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.