Promovido por:
https://orcid.org/0009-0000-3229-5614
El trastorno depresivo mayor (TDM), la depresión resistente al tratamiento (DRT) y la sintomatología depresiva en pacientes con cáncer potencialmente mortal se asocian con una elevada carga de discapacidad y con una respuesta limitada a los tratamientos farmacológicos y psicoterapéuticos estándar. El objetivo de esta revisión narrativa es sintetizar y analizar críticamente la evidencia clínica y neurobiológica reciente sobre la psicoterapia asistida con psilocibina (PAP) en estos cuadros. Se llevó a cabo una búsqueda exhaustiva de la bibliografía (2010–2025) en PubMed, PsycINFO y Scopus, con el fin de identificar estudios clínicos (ensayos abiertos y controlados) y trabajos de síntesis (revisiones sistemáticas, metaanálisis), complementados con evidencia preclínica y de neuroimagen relevante. Los estudios clínicos revisados muestran que una o dos sesiones de psilocibina en dosis moderadas-altas, integradas en un protocolo psicoterapéutico estructurado, producen reducciones rápidas y clínicamente significativas de los síntomas de depresión y ansiedad, con mantenimiento de la respuesta en una proporción de pacientes durante varios meses y, en algunos casos, más de un año. La acción de la psilocibina se basa en el agonismo 5-HT₂A, el incremento de la plasticidad sináptica y la modulación de redes de alto orden, como la red neuronal por defecto (RND). Respecto a la seguridad, se considera aceptable bajo condiciones controladas (cribado, apoyo y terapia), si bien persisten reportes de experiencias desafiantes y riesgo suicida en pacientes con DRT. Se discuten las principales limitaciones metodológicas (tamaños muestrales reducidos, dificultades de enmascaramiento, muestras altamente seleccionadas) y se proponen prioridades para futuras investigaciones clínicas.
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