[Psilocybin in the setting of treatment-resistant unipolar depression: A case report].

Background: Current antidepressants have shown certain limitations in the treatment of unipolar depression. Their long onset of action, interactions, and side effects are obstacles to achieving lasting remission of this prevalent, often chronic or recurrent, pathology. Faced with this clinical necessity, research efforts have intensified in recent years around psychedelic drugs, with a particular focus on the mental health benefits of psilocybin. To illustrate this promising approach, we present here the clinical vignette of a student living in France for whom psilocybin led to complete remission after recurrent depressive episodes and a two-year course of Escitalopram.

Case presentation: Juan, a Mexican student, decided to move to France in 2015 to further his education and broaden his horizons. Since his degree in physiotherapy from Mexico did not qualify him to practice in France, he began studying Biology from 2016 to 2020. Unfortunately, during this period, Juan experienced his first episode of major unipolar depression, marked by feelings of incompetence and academic stagnation. In March 2017, he started an initial course of Escitalopram at 5mg, which provided some relief from his depressive symptoms but did not completely alleviate his anxiety and ruminative thoughts. The treatment was discontinued after three months due to a summer travel plan. By January 2018, he encountered a more intense depressive episode for which he resumed Escitalopram at an increased dose of 10mg. He continued this treatment until August 2019, although it again proved insufficient for full symptom relief. In January 2020, he faced his most challenging relapse, sometimes unable to get out of bed for weeks. This led him to resume Escitalopram, this time at 15mg, but he struggled with significant side effects, including nausea, fatigue, and numbness. Seeking alternative solutions, in the summer of 2020 Juan tried a non-conventional approach in Mexico using psilocybin, a compound found in hallucinogenic mushrooms, under the supervision of a shaman. Following the first administration in July, he noticed a rapid partial improvement in his symptoms; a second administration two weeks later resulted in a full remission of his depressive symptoms. Juan described his experience as profoundly healing, gaining an inner peace and a deep understanding of his struggles. Since 2020, he has remained in full remission without the need for antidepressants. This case highlights the potential role of psilocybin in addressing treatment-resistant depression and the importance of further research into alternative therapeutic options.

Discussion: Psilocybin, a 5-HT2A serotonergic receptor agonist, affects cortical neural networks by reducing amygdala reactivity to negative emotions and altering brain connectivity. According to David Nutt's drug harm scale, psilocybin ranks among the least dangerous substances with a relatively low potential for dependence. Despite its potential benefits, responsible and supervised use is essential. Under carefully prepared conditions, psilocybin's psychedelic effects can promote healing by facilitating introspection and altering depressive brain functioning. In April 2021, a double-blind, randomized trial by a British team at Imperial College London compared psilocybin to Escitalopram, revealing higher response and remission rates for psilocybin : 70% of psilocybin-treated patients experienced a reduction of over 50 % in depression levels, compared to 48 % of those on antidepressants-a 22 % increase. However, with only 59 subjects and a 6-week Escitalopram treatment for the control group, further research with larger samples and extended treatment durations is essential.

Conclusion: The psychedelic experience appears to have significantly accelerated Juan's clinical remission, enabling him to regain control over his life after years of depression. Although multiple factors may have contributed to Juan's recovery-including his course of Escitalopram-psychedelic effects seem to have served as a powerful tool in overcoming his depression. This case suggests additional therapeutic potentials worth exploring, such as the reduction of alcohol consumption.