Adding a single 25 mg dose of psilocybin to an 8-week Mindfulness-Based Stress Reduction (MBSR) program led to a significantly larger reduction in depressive symptoms among frontline healthcare workers than MBSR alone, with no serious adverse events. In a small randomized trial of 25 physicians and nurses with depression and burnout related to the COVID-19 pandemic, the combination group showed a 4.6-point greater drop on the Quick Inventory of Depressive Symptoms at two weeks post-intervention. This advantage diminished by six months. Secondary measures of burnout, demoralization, and connectedness also favored the psilocybin group but did not survive statistical correction. Larger trials are needed to confirm durability and generalizability.
Esketamine nasal spray, a rapid-acting antidepressant for treatment-resistant depression (TRD), was not cost-effective compared with most commonly used third-line strategies in Hong Kong. A Markov model simulated adults with TRD over five years and compared esketamine plus an antidepressant against six alternatives: combination therapy (two antidepressants), augmentation (antipsychotic or lithium), psychotherapy alone, psychotherapy plus antidepressant, repetitive transcranial magnetic stimulation (rTMS) plus antidepressant, and electroconvulsive therapy (ECT) plus antidepressant. Esketamine's incremental cost-effectiveness ratios ranged from US$134,127 to US$312,750 per quality-adjusted life-year (QALY) versus augmentation, combination, psychotherapy, and psychotherapy plus antidepressant—all above a US$50,000/QALY threshold. It was more cost-effective than rTMS (dominated) and ECT (ICER: US$322,407/QALY). Combination therapy was the most cost-effective strategy. Findings rely on indirect comparisons and may not reflect real-world patients.
Among 9.3 million people in Ontario, those who had an emergency department visit or hospitalization involving hallucinogens faced a 6-fold higher risk of a first episode of mania and a nearly 4-fold higher risk of a new bipolar disorder diagnosis over three years, compared to similar individuals without such acute care. The absolute risk was low: 1.43% of those with hallucinogen-related acute care developed mania versus 0.06% in the general population. The findings apply only to people who required acute care for hallucinogen use, not to most users, and suggest caution for individuals at risk of bipolar disorder.