Pα+ Psychedelic Bulletin #165: A Closer Look at a Buzzy Oral Ketamine for Depression Study; UN Weighs In on Psychedelics; Another CA Psychedelics Bill Fails

Phase 2 Study of Oral Ketamine for Depression Lauded by Media and Sponsor, Yet Closer Look Reveals Underwhelming Results

Earlier this week, a Phase 2 study of extended-release ketamine tablets for treatment-resistant depression (TRD) published in Nature Medicine (Glue et al., 2024). The study (dubbed BEDROC; ACTRN12618001042235) was sponsored by Douglas Pharmaceuticals, a New Zealand-based drug manufacturer, which is developing the 60mg ketamine tablets under the moniker R-107.

The study enrolled patients diagnosed with TRD who had failed two or more antidepressants during their current period of depression and—via a two-part design (more below)—administered various doses of its oral ketamine tablets over the course of thirteen weeks.

The study reported a mean difference of MADRS score between the 180mg group and placebo of -6.1 at week 13, a “statistically significant and clinically meaningful improvement in depressive symptoms”,

Lead author Paul Glue, speaking via a company press release, said that the study “shows that it is possible to achieve a robust anti-depressant response from ketamine without significant dissociation”, and that it “gives us confidence to proceed to pivotal registrational clinical studies.”

With a hefty Altmetric score of over 400 and coverage by more than fifty news outlets, the study has certainly made a splash in favour of this ketamine formulation’s supposed efficacy and safety.

However, a closer look at the study design, and headline results, reveals a much less flashy picture...