A multi-centre trial across four Canadian institutions will compare intravenous ketamine infusions with electroconvulsive therapy (ECT) for treating major depressive episodes in 240 patients with major depressive or bipolar disorder. Patients are randomized to either ECT or ketamine three times per week for three to four weeks; non-responders cross over to the other treatment. Responders enter a six-month maintenance phase. The primary outcome is change in depression severity scores assessed by blinded raters. The study aims to identify clinical, molecular, and imaging predictors of response to each treatment.
Intravenous ketamine effectively treats bipolar depression, but its side-effect of dissociation can be distressing and treatment-limiting. Two patients with bipolar 1 disorder and severe depression received their first ketamine infusion without music and chose music for subsequent infusions. They reported that music improved tolerance of dissociative symptoms, reducing distress and aiding further treatments. Both achieved remission from treatment-resistant depression after six infusions. This is the first report of music's benefits with ketamine for bipolar 1 depression, building on prior research with psychedelics. Principles of music selection from that paradigm may apply to unipolar and bipolar depression, warranting further research.