What is the efficacy of psilocybin-containing mushrooms for treatment-resistant depression (TRD)?

From the Guidelines

Psilocybin mushrooms should not be used for treating treatment-resistant depression outside of clinical trials or approved therapeutic settings due to limited evidence and potential risks. The use of psilocybin for depression has been studied in a limited number of patients, with one study showing improved depressive symptoms at weeks 5 and 8 in patients who received immediate therapy with psilocybin compared to those who received it after an 8-week waiting period 1. However, the guideline recommends against its use due to concerns about the risk of psychotic events and harmful behaviors in patients who do not receive appropriate guidance throughout the treatment process, as well as the potential for dependence 1.

Key Considerations

• The treatment of treatment-resistant depression typically involves the use of medications such as esketamine, which has been shown to be effective in patients who have previously not responded to trials of antidepressants 1.
• Psilocybin therapy requires health care providers to help prepare and guide the patient through the treatment, which usually lasts 8 to 12 hours 1.
• The potential benefits of psilocybin therapy must be weighed against the risks of adverse effects, including temporary anxiety, confusion, elevated blood pressure, and nausea during the experience.
• Clinical trials are currently underway to further evaluate the efficacy and safety of psilocybin for treatment-resistant depression, and patients should only pursue this treatment through approved clinical trials or therapeutic settings 1.

Recommendations for Treatment-Resistant Depression

• Esketamine may be considered for patients who have previously not responded to trials of antidepressants, but it is not recommended as an initial treatment due to the risk of adverse effects and the limited information on long-term consequences 1.
• Repetitive transcranial magnetic stimulation (rTMS) may also be considered for patients with treatment-resistant depression, as it has been shown to be effective in improving symptoms and facilitating remission, with minimal and manageable adverse events 1.

From the Research

Treatment-Resistant Depression

• Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder that does not respond to traditional and first-line therapeutic options 2.
• Depression is often a chronic illness that requires a methodical, long-term approach to manage it optimally, and a single antidepressant trial is often insufficient for patients to achieve remission 3.
• Strategies that can be effective to combat treatment resistance include optimizing treatment, switching to another antidepressant, combining antidepressants, and augmenting antidepressants with nonantidepressant treatments such as buspirone, lithium, liothyronine, atypical antipsychotics, or other agents 3, 4.

Psychotherapies for Treatment-Resistant Depression

• Moderate-quality evidence shows that psychotherapy added to usual care (with antidepressants) is beneficial for depressive symptoms and for response and remission rates over the short term for patients with TRD 5.
• Psychotherapy added to usual care seems as acceptable as usual care alone, with high-quality evidence showing no differential dropout between intervention and comparator groups over the short term 5.
• Different types of psychotherapies may be used for TRD, including cognitive-behavioural therapy (CBT), intensive short-term dynamic psychotherapy (ISTDP), interpersonal therapy (IPT), and group dialectical behavioural therapy (DBT) 5.

Novel Therapeutics for Treatment-Resistant Depression

• Novel therapeutics, including ketamine and psilocybin, are being reviewed for the treatment of TRD, but further large-scale work is necessary to understand the appropriate treatment pathways and to prescribe effective therapeutic options for patients suffering from TRD 2.
• There is no mention of mushrooms specifically in the provided studies, but psilocybin, which is a naturally occurring psychedelic compound found in certain species of mushrooms, is being researched as a potential treatment for TRD 2.

Limitations and Future Directions

• Further evidence is needed on the effectiveness of different types of psychotherapies for patients with TRD, as well as the comparison of switching to a psychotherapy versus continuing an antidepressant medication regimen 5.
• The management of TRD is complex and requires a comprehensive approach, including pharmacological augmentation strategies, somatic therapies, and psychotherapeutic strategies 2.