Combined Treatment with Corticosteroids and Moclobemide Favors Normalization of Hypothalamo-Pituitary-Adrenal Axis Dysregulation in Relapsing-Remitting Multiple Sclerosis: A Randomized, Double Blind Trial

Abstract

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 ± 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0–6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 ± 76.8 arbitrary units in the moclobemide group vs. 225.8 ± 65.1 in the steroid alone group; mean ± sem]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 ± 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 ± 22.8 vs.177.1 ± 68.5; on day 75, 111.0 ± 46.0 vs. 199.2 ± 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.