Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression

Summary & key facts

Researchers tested a single dose of a lab-made psilocybin pill for people whose depression had not improved with other treatments. About 80 people got 25 mg, 75 got 10 mg, and about 80 got 1 mg, and everyone also had psychological support. After three weeks, the highest dose (25 mg) reduced depression scores more than the tiny 1 mg dose, but the mid dose (10 mg) did not show a clear benefit. Side effects were common and included headache, nausea, and dizziness, and thoughts of suicide or self-harm occurred across all groups. The early benefit at three weeks did not clearly last to 12 weeks, and the researchers said bigger and longer studies are needed to know if psilocybin is safe and truly helpful compared with current treatments.

Key facts:

• This was a phase 2 trial of people with treatment-resistant depression who were randomly given one single dose of synthetic psilocybin at 25 mg, 10 mg, or 1 mg, plus psychological support.
• About 80 people were in the 25 mg group, 75 in the 10 mg group, and about 80 in the 1 mg group.
• At the start, average depression scores were about 32 out of 60, indicating moderate-to-severe depression.
• After three weeks, average depression scores dropped by roughly 12 points with 25 mg, 8 points with 10 mg, and 5 points with 1 mg.
• The 25 mg dose reduced scores about 7 points more than the 1 mg dose, a difference the researchers reported as unlikely to be due to chance; the 10 mg dose did not show a clear advantage over 1 mg.
• The 25 mg group had higher rates of response (at least half the improvement) and remission (low symptom score) at three weeks, but those benefits were not clearly kept at 12 weeks.
• Side effects happened in about 77% of participants and included headache, nausea, and dizziness. Reports of suicidal thoughts, suicidal behavior, or self-injury occurred in every dose group.
• The authors said larger and longer trials, and comparisons with existing treatments, are needed to decide whether psilocybin is an effective and safe option for this kind of depression.

Abstract

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

Topics

Forensic Toxicology and Drug Analysis Pain Management and Placebo Effect Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Antidepressant Anxiety Depression (economics) Economics Hallucinogen Keynesian economics Medicine Psilocybin Psychiatry Psychology Treatment-resistant depression

Substances

Psilocybin

Conditions & symptoms

Anxiety Depression Lack of energy or motivation Sadness or low mood