Psilocybin May Reduce Treatment-Resistant Depression in Bipolar Type II

Psilocybin with psychotherapy may be safe and effective for treatment-resistant depression among patients with bipolar type II disorder, according to a small, open-label, nonrandomized, controlled trial published in JAMA Psychiatry.

Treatment options for depressive episodes are limited for patients with bipolar type II disorder. Psilocybin is derived from psilocybin mushrooms and when ingested creates mind-altering effects that have been associated with increased associative learning, cognitive flexibility, and neuroplasticity. These effects may have a therapeutic effect in treating depression.

Read more: Bupropion for Treatment-Resistant Depression

Researchers conducted a 12-week study (ClinicalTrials.gov Identifier: NCT04433845) between 2021 and 2023 at the Sheppard Pratt Health System in the United States. Patients (N=15) with bipolar type II disorder in a current depressive episode who had documented insufficient benefit from 2 or more pharmacologic treatments underwent a 3- to 6-week run-in period to washout antidepressants, mood stabilizers, stimulants, and benzodiazepines. On the dosing day, participants received a single 25 mg synthetic psilocybin dose in attendance with a lead therapist and assistant therapist during an 8- to 9-hour day. After dosing, participants returned for 3 1-hour integration sessions at weeks 1, 3, and 12.

The primary efficacy outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 3 weeks.

Among the 15 participants (mean age, 37.8; 60% women; 80% White), 46.7% had a history of psychiatric hospitalization, 33.3% had a prior suicide attempt, and the duration of the current depressive episode was 30.2 months.

At baseline, MADRS score was 31.3. At 3 weeks, the average decrease in MADRS score was -24.00 which corresponded with a 76.3% reduction from baseline (t_[14], 10.07; P <.001). The average MADRS score did not differ significantly between weeks 1, 3, and 12 assessments, indicating stable effects posttreatment.

Psilocybin dosing also had significant effects on Quick Inventory of Depression Symptoms-Self Rating (QIDS-SR) scores (d, 2.00; P =.001) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) scores (d, 1.80; P <.001) from baseline to week 3, mania symptoms were reduced (F_[3,42], 2.85; P =.049), and no patient attempted or committed suicide.

No significant adverse events related with psilocybin dosing were reported. The most common adverse event (n=4) was headache on the day of dosing which resolved within 24 hours.

At the end of the study, 9 patients did not restart their antidepressants or mood stabilizing medications.

The major limitation of this study was the lack of a control group.

“The findings support further study of psychedelics in the [bipolar disorder type II] population. Consideration should be given as to whether administration of psilocybin affects the high risk of substance use disorders in the [bipolar disorder] population,” the researchers concluded.

Disclosures: This research was supported by COMPASS Pathways. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.