Selective serotonin reuptake inhibitors (SSRIs) are the dominant treatment for major depressive disorder (MDD). Recent studies with psychedelics have most often been with patients not currently taking SSRIs. SSRI withdrawal can be a disruptive experience. We previously completed a study which reported positive results with SPL026 (DMT fumarate) in patients with MDD (without SSRIs), with a mean difference between active and placebo at 2 weeks of -7.35 (Montgomery-Asberg Depression Rating scale (MADRS)) (p=0.023).

This open-label study investigated the safety, tolerability, pharmacokinetics, pharmacodynamics and exploratory efficacy of a single SPL026 intravenous dose, alone or in combination with SSRIs. The test cohort (N=12) (“SSRI-Cohort”) consisted of patients currently on a stable, but not fully effective, treatment of SSRIs. The control (N=5) (“Non-SSRI-Cohort”) consisted of patients not currently using any pharmacological antidepressant treatment. Patients were recruited with a Hamilton Depression Rating Scale score of ≥14.

We observed no drug-related SAEs, 8 drug-related AEs in SSRI-Cohort, and 3 in Non-SSRI Cohort, all of which were mild-moderate, with the majority resolving during the dosing visit. Exploratory efficacy measures at 4 weeks found: mean MADRS change in SSRI-Cohort of -25.8 and -19.4 in Non-SSRI-Cohort; % response was 100% in SSRI-Cohort and 80% in Non-SSRI-Cohort; % remission was 92% in SSRI-Cohort and 20% in Non-SSRI-Cohort.

These results suggest that patients can safety continue their use of antidepressants while undergoing psychedelic treatment and that, in fact, it may be beneficial for patients to remain on their ongoing SSRIs.