A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania

• DOI: 10.1007/s00213-020-05654-1
• Publication Date: 2020-09-10T12:53:09Z
• Authors: Ann L Sharpley; Clare Williams; Adele A Holder; Beata R Godlewska; Nisha Singh; Milensu Shanyinde; Orla MacDonald; Philip J Cowen
• Keywords: Hypomania; Ebselen

Lithium is an effective prophylactic and anti-manic treatment in bipolar disorder; however, its use declining through perceived poor tolerance toxicity. inhibits inositol monophosphatase (IMPase), a probable key therapeutic mechanism. The anti-inflammatory drug, ebselen, also IMPase appears well-tolerated safe.To assess the efficacy of adjunctive ebselen mania using Young Mania Rating Scale (YMRS) (primary outcome) Altman Self-Rating (ASRM) Clinical Global Impression-Severity (CGI-S) among secondary outcomes.Randomised, double-blind, placebo-controlled, parallel-group trial conducted between October 2017 June 2019, at Oxford Health NHS Foundation Trust. Pharmacy-controlled randomisation was computer-generated, with full allocation concealment. In/outpatients (n = 68) aged 18-70, experiencing or hypomania, were assigned to 3 weeks (600 mg bd) 33) placebo 35). Participants received usual clinical care psychotropic medication.Ebselen numerically, but not statistically, superior lowering scores on YMRS (adjusted mean difference 95% confidence interval, - 1.71 (- 5.34 1.91), p 0.35) ASRM 1.36 3.75 1.17), 0.29). However, CGI-S significantly lower week ebselen-treated participants difference, 0.58 1.14 0.03), 0.04). A post hoc analysis excluding patients taking concomitant valproate magnified YMRS. Adverse events comparable groups, mild.Ebselen merits further investigation where medication better controlled are excluded. If effective, ebselen's safety could make it useful alternative lithium.Trial Registry: www.clinicaltrials.gov , Identifier: NCT03013400.