Treatment-Resistant Depression (TRD)Depressive DisordersAnxiety DisordersSet & Setting

Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments

This meta-review (2020) examines the therapeutic frameworks surrounding contemporary practices of psychedelic-assisted psychotherapy, with regard to the historic development of therapeutic models and contemporary insights into extra-pharmacological factors and underlying mechanisms. They highlight that these therapies entail greater environmental sensitivity from the patient's perspective, which requires more meticulous attention for the preparation of the set and setting, a considerably resource-intensive endeavor.

Authors

  • Lisa Jerome
  • Anna Feduccia
  • Kyle Greenway

Published

Expert Review of Clinical Pharmacology
meta Study

Abstract

Introduction

Combinations of psychotherapy with antidepressants are gold-standard psychiatric treatments. They operate through complex and interactional mechanisms, not unlike the reemergent paradigm of psychedelic-assisted psychotherapy, which promising research suggests may also be highly effective in even challenging populations.Areas covered: We review the therapeutic mechanisms behind both conventional and psychedelic paradigms, including the evolution of this knowledge and the associated explanatory frameworks. We explore how psychedelics have provided insights about psychiatric illnesses and treatments over the past decades. We discuss limitations to early explanatory models while highlighting and comparing the psychological and biological mechanisms underlying many psychiatric treatments.

Methods

A narrative review was conducted based on a search in Medline/Pubmed up to January 1st, 2020, and iterative retrieval of references from recent reviews and clinical trials.Expert opinion: The contextual model of the common factors of psychotherapy provides a powerful perspective on psychotherapy, antidepressants, and psychedelics, as well as 3,4-methylenedioxymethamphetamine (MDMA) and ketamine. It aligns well with key tenets of psychedelic-assisted psychotherapy. Conventional antidepressants and especially psychedelics may improve the efficacy of psychotherapy via neurochemical changes and increased environmental sensitivity. Combined treatments hold significant promise for advancing the knowledge and treatment of many forms of psychopathology.

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Research Summary of 'Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments'

Introduction

Psychiatric disorders are common and account for a growing share of global morbidity, with depression and anxiety responsible for roughly half of this burden. Existing treatments—psychotherapy and pharmacotherapy—are generally effective but many patients remain treatment-resistant, creating demand for new approaches. Recent regulatory attention and industry activity have focused on treatments that intentionally combine psychoactive compounds with structured psychotherapy, such as psilocybin-assisted psychotherapy and MDMA-assisted psychotherapy, alongside developments like intranasal esketamine for treatment-resistant depression. The terminology around these agents varies: classical psychedelics (e.g. LSD, psilocybin) are typically 5HT2A agonists, MDMA is often described as an entactogen or empathogen, and ketamine as a dissociative; all can induce temporary, profound alterations of consciousness that may be harnessed therapeutically. Greenway and colleagues set out to review the principles, history, mechanisms, and clinical results of psychedelic-assisted psychotherapy (PAP), with emphasis on LSD and psilocybin. The review also places PAP in the broader context of conventional psychotherapy and antidepressant pharmacology, aiming to clarify shared and distinct mechanisms whereby combined psychotherapeutic and pharmacological treatments may produce benefit.

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Study Details

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