Objective:

To evaluate the tolerability, potential efficacy, and time to potential efficacy
Of Maraviroc for post-stroke depression(PSD).

Background:

Depression and anxiety affect up to 60% of stroke survivors; they play a critical role in shaping long-term stroke outcome. Currently effective therapeutic options are relatively few.
Recent studies by our group and colleagues showed that the FDA-approved HIV-drug, maraviroc, a CCR5-antagonist, improved cognitive function in a rodent stroke model. Maraviroc modulates several signaling cascades implicated in learning, memory and depression. We have recently reported that in a large clinical stroke patients cohort, carriers of a natural-occurring mutation that blocks CCR5, had reduced depressive symptoms, anxiety and cognitive deficits two-years post-stroke. Based on that we conducted the first open pilot-trial using Maraviroc as augmentation treatment in PSD patients who failed to achieve remission after adequate psychopharmacologic treatment.

Design/Methods:

A 10-week, open-label, proof-of-concept trial of daily-oral 300mg Maraviroc was conducted in treating recent subcortical stroke patients suffering from PSD. Subjects were followed for another 8-weeks after completing treatment. Response rate defined as a reduction in Montgomery-Asberg-Depression-Rating Scale(MADRS) from baseline to week-10 of >30%, and remission rate as MADRS score at week-10 of <10. Subjects completed the quick-inventory of depressive symptoms-self report(QIDS-SR16) score.

Results:

MADRS score was reduced from baseline to week-10(mean change:−16.4±9.3,p <0.001), as was the QIDS-SR16 score(mean change:−6.5±6.4,p=0.01).
At the end of 10-weeks Maraviroc augmentation, 70%(7/10) of the patients achieved response and 40%(4/10) achieved remission, with shorter time-to-response than current antidepressants in use. Some of the responders(4/7) experienced worsening of their depressive symptoms after stopping the study drug(6/7). Maraviroc was well tolerated with no reported adverse events or discontinuation due to intolerance.

Conclusions:

Our proof-of-concept study suggests that Maraviroc 300mg/day may be an effective and well-tolerated pharmacological treatment option for PSD.
Larger placebo-controlled studies are needed to evaluate the effects of Maraviroc augmentation in post-stroke depressive patients.