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

This is a double blind RCT published on September 9 2020 in the journal of Psychopharmacology. In this RCT they investigated the efficacy of a selenium containing drug called ebselen in patients with bipolar disorder. Ebselen inhibits the inositol monophosphate pathway similar to Lithium which is an effective first line medication bipolar disorder. An earlier study indicated that a 1200 mg dose of ebselen daily is sufficient to interact with IMPase in the human brain and decrease the availability of inositol. It is also important to indicate that in addition to the inhibiting IMPase, lithium also inhibits the glycogen synthase kinase 3 pathway (GSK3). In this RCT they recruited a cohort of 60 bipolar patients, most were female with ages ranging from 18-70 years old. Of the 60 patients, 27 were given ebselen and 33 were given placebo. Both interventions were given for a total of 4 weeks. Treatment outcomes were measured using the Young Mania Rating Scale and the Altman Self-rating mania. After week 3, patients in the ebselen group were no longer given the active medication and were given placebo alongside the placebo group. Assessments made during this week were given particular attention because the researchers wanted to see if the patients felt any noticeable difference when taken off ebselen. In all, the researchers found that there was not initial statistical significance between the two groups. However, although the researchers excluded patients on lithium from participating in the trial, they did not exclude those taking valproate, which is an alternative mood stabilizer. In an additional post hoc analysis, the researchers tried to account for the participants that were on valproate. This analysis created a significant difference between the ebselen+valproate group and the placebo+valproate group. In summation this article touches on a potentially promising new medication that might be an alternative to lithium in the future, however the efficacy of this medication needs further research. In future studies they should try to limit the number of patients on ancillary mood-stabilizing medications.