This phase IIa clinical trial evaluates the efficacy of using a brief intravenous infusion of dimethyltryptamine (DMT), a classic serotonergic psychedelic, for the treatment of major depressive disorder. This study is interesting because of its novelty, as it is the first clinical trial to specifically evaluate the efficacy of this intervention, although it is supported by previous evidence of its safety and robust data supporting the antidepressant effects of interventions with DMT-containing compounds, such as ayahuasca. In addition, the nature of the intervention (a brief 10-minute infusion, accompanied only by a preparation session and an integration session, with an acute duration of psychedelic effects of around 30 minutes) greatly facilitates its large-scale implementation, compared to other interventions with other psychedelics, such as psilocybin, which require the patient to remain under observation for up to eight hours, and several preparation and integration sessions. The results are promising, showing a significant improvement in depressive symptoms, which is already observed from the first week and sometimes lasts up to six months.
However, it is important to contextualise the findings, as the study has serious limitations: the sample size is small (only 17 patients per arm), and the open-label design only allowed the efficacy of the treatment to be evaluated against placebo for two weeks, as after this period all patients received a second dose. Although the subsequent improvement was maintained for up to three months, it is not possible to determine the contribution of the placebo effect or other contextual factors. It is also important to note that interesting numerical differences were observed, such as differences in improvement between patients who received one dose and those who received two, which did not reach statistical significance.
Nevertheless, the study design and reporting of results are very rigorous, reinforce previous data on the efficacy and tolerability of this intervention, and open the door to further trials with larger sample sizes. If these data are verified, they could lead to the development of brief interventions that would facilitate access to these therapies and their implementation in public health systems.