Banca de QUALIFICAÇÃO: DANIEL AMORIM SERAFIM

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : DANIEL AMORIM SERAFIM
DATE: 10/02/2026
TIME: 09:00
LOCAL: REMOTA
TITLE:

LONG-TERM OUTCOMES IN TREATMENT-RESISTANT DEPRESSION: A 12-MONTH FOLLOW-UP OF A PHASE 2A OPEN-LABEL TRIAL OF VAPORIZED N,N-DIMETHYLTRYPTAMINE

KEY WORDS:

N,N-dimethyltryptamine; treatment-resistant depression; psychedelic-assisted therapy; long-term follow-up; suicidality; functionality.

PAGES: 17
BIG AREA: Ciências da Saúde
AREA: Saúde Coletiva
SUMMARY:

Background: Available pharmacotherapies for treatment-resistant depression (TRD) require daily dosing and often present delayed and limited effects on symptoms and functional impairment, with no immediate anti-suicidal action. In contrast, clinical research on serotonergic psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) has shown rapid and sustained antidepressant and anti-suicidal effects following minimal dosing sessions. However, long-term follow-up studies remain scarce, a critical limitation given that approximately 70% of patients with depression relapse within three months, even under continued treatment.

Methods: This long-term follow-up work evaluated 14 participants from a phase 2a open-label clinical trial with unipolar TRD. Participants received two inhaled doses of vaporized DMT: a 15 mg dose for safety assessment and a 60 mg therapeutic dose, followed by integration sessions immediately after administration and at 1 and 7 days post-dose. Depressive symptoms, suicidal ideation, and functionality were assessed respectively by the Patient Health Questionaire (PHQ9), Beck Inventory for Suicidality (BSI) and the World Health Organization Disability Assessment Schedule (WHODAS), at baseline (D0) and multiple time points up to 12 months (M12), including a qualitative assessment exclusively at M12.

Results: Twelve participants completed the 12-month follow-up from the original trial that included 14 adults (aged 21–54). At M12, PHQ-9 scores were significantly lower than D0 (t(11)=4.33, p=0.001), with remission rates on 3/12 of participants (25%) and response on 4/12 (33%). Suicidal ideation decreased substantially: 83% of participants did not report suicidal ideation at M12 versus 28% at D0. WHODAS did not reach statistical significance for functionality, despite numerical improvement. Qualitative data describing participants’ clinical status and treatment trajectories at M12 indicated perceived improvements in depressive symptoms, including social withdrawal, cognitive impairment, and will to live, which were predominantly described as occurring within the first three months following the intervention.

Conclusion: This long-term follow-up of a phase 2a open-label trial with vaporized DMT in patients with TRD showed significant reductions in depressive symptoms and suicidality lasting up to 12 months. Although functionality scores were reduced without reaching statistical significance, integration with qualitative data suggests that long-term effects in TRD may be better understood as changes in symptom burden alongside individualized recovery trajectories. Despite limitations related to sample size, open-label design, and the absence of a control group, this study contributes novel longitudinal data on the clinical effects of vaporized DMT and supports the need for controlled and multicenter trials designed to assess durability of response.

COMMITTEE MEMBERS:
Presidente - 1243905 - DRAULIO BARROS DE ARAUJO
Externa à Instituição - GEISSY LAINNY DE LIMA ARAÚJO - UFRN
Externo ao Programa - 1323908 - JOAO CARLOS ALCHIERI - null