From the Guidelines
Psilocybin should not be used as a treatment for depression outside of clinical trials due to limited evidence on its safety and efficacy. The most recent and highest quality study, published in 2022 in the Annals of Internal Medicine 1, recommends against the use of psilocybin for the treatment of depression, citing concerns about the risk of psychotic events and harmful behaviors in patients who do not receive appropriate guidance throughout the treatment process.
Key Considerations
- The study found that psilocybin therapy requires healthcare providers to help prepare and guide the patient through the treatment, which can last 8 to 12 hours 1.
- There is a potential for dependence and limited information on the long-term consequences of psilocybin therapy 1.
- The guideline recommends against the use of psilocybin, as well as other unapproved pharmacologic agents, in settings outside clinical trials 1.
Current Recommendations
- Ketamine and esketamine are not recommended as initial treatment for depression, but are reserved for patients for whom previous therapies have failed or who have not tolerated previous therapies 1.
- Psilocybin therapy should only be pursued through legal clinical trials or in jurisdictions where it has been approved for therapeutic use, always under professional supervision.
- Patients with psychotic disorders, severe cardiovascular disease, or those taking certain medications like SSRIs shouldn't be considered for psilocybin therapy due to potential contraindications.
From the Research
Psilocybin for Depression
- Psilocybin has been examined as a promising alternative to traditional first-line options for treating major depressive disorder (MDD) 2.
- Studies have shown that psilocybin administration can lead to a decrease in amygdala activity and a reduction in depressive symptoms 2.
- Changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, have been observed in healthy populations after psilocybin administration 2.
- Meta-analyses have found that psilocybin can be effective in reducing symptoms of depression and anxiety in patients with life-threatening diseases 3.
- The therapeutic potential of psilocybin and other psychedelics, such as MDMA, has been highlighted as a possible alternative avenue of therapy for mental health disorders, including depression 4.
Comparison to Traditional Treatments
- Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, fluoxetine, and citalopram, are commonly used to treat depression, but may have limitations, including initial lack of response, drowsiness, nausea, and sexual dysfunction 5.
- Long-term follow-up studies have shown that SSRIs may have limited prophylactic efficacy in preventing recurrence of major depressive disorder, with a recurrence rate of 82.0% for SSRI-only treatment 6.
- Concomitant cognitive behavioral therapy (CBT) may improve the prophylactic efficacy of SSRIs, with a recurrence rate of 59.0% for patients receiving both CBT and SSRI treatment 6.
Future Research Directions
- Longitudinal studies are needed to further elucidate the effects of psilocybin on MDD, its long-term effects, and the possibility of sustained therapeutic effects 2.
- Novel clinical trials are warranted to evaluate the safety, tolerability, and efficacy of psilocybin in clinically representative populations 4.