Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Controlled Trial.

Importance: Bipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression. Objective: To establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode. Design, Setting, and Participants: This was a 12-week, open-label nonrandomized controlled trial conducted at Sheppard Pratt Hospital. Participants aged 18 to 65 years with BDII, a current depressive episode longer than 3 months, and documented insufficient benefit with at least 2 pharmacologic treatments during the current episode were invited to participate. Of 70 approached, 19 met inclusion criteria and were enrolled. The trial was conducted between April 14, 2021, and January 5, 2023. Interventions: A single dose of synthetic psilocybin, 25 mg, was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing. Therapists met with patients for 3 sessions during pretreatment, during the 8-hour dosing day, and for 3 integration sessions posttreatment. Main Outcomes and Measures: The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures included MADRS scores 12 weeks posttreatment, the self-rated Quick Inventory of Depression Symptoms-Self Rating (QIDS-SR), and the self-rated Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), each completed at baseline and all subsequent visits. Safety measures included the Columbia Suicide Severity Rating Scale (CSSRS) and the Young Mania Rating Scale (YMRS) completed at each visit. Results: Of the 15 participants in this study (6 male and 9 female; mean [SD] age, 37.8 [11.6] years), all had lower scores at week 3, with a mean (SD) change of -24.00 (9.23) points on the MADRS, (Cohen d = 4.08; 95% CI, -29.11 to -18.89; P < .001). Repeat measures analysis of variance showed lower MADRS scores at all tested posttreatment time points, including the end point (Cohen d = 3.39; 95% CI, -33.19 to -16.95; adjusted P < .001). At week 3, 12 participants met the response criterion (50% decrease in MADRS), and 11 met remission criterion (MADRS score ≤10). At the study end point, 12 patients met both response and remission criteria. QIDS-SR scores and Q-LES-Q-SF scores demonstrated similar improvements. YMRS and CSSRS scores did not change significantly at posttreatment compared to baseline. Conclusions and Relevance: The findings in this open-label nonrandomized controlled trial suggest efficacy and safety of psilocybin with psychotherapy in BDII depression and supports further study of psychedelics in this population.

Optimizing outcomes in psilocybin therapy: Considerations in participant evaluation and preparation.

Recent studies have demonstrated the promise of psilocybin therapies in creating positive changes for those with poor mental health across multiple diagnostic categories, including major depressive disorder (MDD), end-of-life anxiety, and obsessive-compulsive disorder (OCD). While there may be a large population that is eligible to participate in psilocybin therapy based on psychiatric diagnosis and medical clearance, little attention has been given to intrapersonal and interpersonal factors that might influence patient's readiness (i.e., eligibility and capacity) for psychedelic interventions. This paper proposes that readiness assessment includes both intrapersonal and interpersonal factors in order to improve safety, patient care, and treatment outcomes. While at the present time a reliable and valid instrument has not been developed, we propose that three specific areas of focus - patient presentation, therapeutic alliance, and patient safety - may be used to establish a patient's readiness for psilocybin therapy, thus increasing therapy optimization and personalization.

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

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.).

Beyond Pills: Acupressure Impact on Self-Rated Pain and Anxiety Scores.

Objectives: To determine impact of an acupressure protocol on self-rated pain and anxiety scores. Design: Retrospective database analysis of self-rated pain and anxiety scores before and immediately after administration of stress release acupressure protocol. Participants: Participants include hospitalized patients, nurses, and public. Intervention: Involves a 16-point stress release acupressure protocol. Outcome measures: Outcome measures involve pre- and post-treatment self-rated pain scores (0-10) with the Wong-Baker Faces Scale and pre- and post-treatment self-rated anxiety scores (0-10) on a visual analog scale. Results: Five hundred and nineteen acupressure treatments were retrospectively analyzed with pre- and post-treatment self-rated pain and anxiety scores, where 0 represented no pain or anxiety and 10 represented the worst pain and anxiety. Overall, participants demonstrated a two-point decrease in pain scores and a four-point decrease in anxiety scores post-treatment. Hospitalized patients demonstrated a four-point decrease in pain scores and a five-point decrease in anxiety scores post-treatment. Nurses demonstrated a three-point decrease in pain scores and four-point decrease in anxiety scores post-treatment. Public population demonstrated a one-point decrease in pain scores and two-point decrease in anxiety scores post-treatment. Seventy-five percent of participants were highly satisfied with acupressure treatments, and 96% of treatments were administered in less than 30 minutes. Conclusions: Acupressure is a highly satisfactory complementary therapy that can demonstrate a clinically significant decrease in self-rated pain and anxiety scores.

Causes of uveitis in dogs: 102 cases (1989-2000).

Uveitis is one of the most common ocular diseases and one of the most common causes of blindness in dogs. The purpose of this retrospective study was to correlate the signalment, history, clinical signs and ophthalmic findings of dogs with uveitis with the underlying etiology. We conducted a retrospective study of 102 dogs presented to the NCSU-VTH from 1989 to 2000 with clinical signs of uveitis. Medical records of dogs presented for uveitis were reviewed. Dogs were included in the study only if a complete diagnostic work-up database was collected, if sufficient follow-up was documented, and if the uveitis was not secondary to trauma or a hypermature cataract. The mean age +/- SD of all dogs in this study was 6.2 +/- 3.6 years. There were 33 intact and 16 castrated males, and 14 intact and 27 neutered females. Fourteen breeds were represented, with the Golden Retriever (n = 14) most common. Fifty-nine dogs (58%) were diagnosed with idiopathic/immune-mediated uveitis, neoplasia was diagnosed in 25 dogs (24.5%) and 18 dogs (17.6%) were diagnosed with infectious causes of uveitis. Aqueous flare was the most common clinical sign, occurring in 88 dogs (86%). The most common infectious organisms associated with uveitis in the dogs of this study were Ehrlichia canis (n = 7). Lymphosarcoma (n = 17) was the most common neoplasm. In approximately 60% of dogs presenting for uveitis an underlying cause was not found, and a diagnosis of immune-mediated or idiopathic uveitis was made. However, approximately 25% of dogs had ocular and/or systemic neoplasia (with 17% of cases having lymphosarcoma) and 18% with an underlying infectious cause for uveitis. Because of the high percentage of systemic disease associated with uveitis in dogs, extensive diagnostic testing is recommended before instituting symptomatic anti-inflammatory therapy.