Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial.

Fernanda Palhano-Fontes,Emerson Arcoverde,Jordi Riba,Bruno Lobão-Soares,Flávia L Osório,Jessica A Pessoa,Luís Fernando Tófoli,Francisco R Santos,Heloisa Onias,Antonio A Silva-Junior,Sérgio A Mota-Rolim ,João Paulo Maia‐De‐Oliveira ,Maurı́cio Yonamine ,Rafael Faria Sanches ,Geraldo Silveira ,Jaime Eduardo Cecílio Hallak ,Dayanna Patrícia De Carvalho Barreto ,Rafael G Dos Santos ,Kátia C Andrade ,João Carlos Alchieri ,Nicole Leite Galvão-Coelho ,Morgana Menezes Novaes ,Dráulio Barros De Araújo

doi:10.1017/s0033291718001356

Abstract

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing. We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen's d = 0.84; D2: Cohen's d = 0.84; D7: Cohen's d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054). To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered at http://clinicaltrials.gov (NCT02914769).

Highlights

The World Health Organization estimates that more than 300 million people suffer from depression (World Health Organization, 2017), and about one-third do not respond to appropriate courses of at least three different antidepressants (Conway et al, 2017)
Hamilton Depression Rating scale (HAM-D) remission rate showed a trend toward significance at D7: 43% in ayahuasca v. 13% in placebo [Odds ratio (OR) 4.87; p = 0.07; number needed to treat (NNT) = 3.39]
Response rates were high for both groups at D1 and D2 and were significantly higher in the ayahuasca group at D7

Summary

Introduction

The World Health Organization estimates that more than 300 million people suffer from depression (World Health Organization, 2017), and about one-third do not respond to appropriate courses of at least three different antidepressants (Conway et al, 2017). In recent randomized placebo-controlled trials with ketamine in treatment-resistant depression, the antidepressant effects peaked 1 day after dosing and remained significant for about 7 days (Berman et al, 2000; Zarate et al, 2006; Murrough et al, 2013; Lapidus et al, 2014). Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. This study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

Methods

Results

Conclusion