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Study Findings Support Esketamine and Psilocybin as Effective TRD Treatments

Meagan Thistle

To address the challenges and “inadequate outcomes” with monoamine-based therapies, a Toronto-based research team investigated the novel alternatives for the treatment of treatment-resistant depression (TRD). The systematic review of 65 randomized controlled trials compared the effects of oral psilocybin and intranasal esketamine in conjunction with oral antidepressants on adults with TRD. Review findings were published in The Journal of Affective Disorders.

“Relatively few pharmacologic agents are proven safe and effective in adults with TRD,” researchers wrote in the study. “We delimit our scrutiny to the foregoing 2 agents as both have received ‘breakthrough’ status by the FDA and are highly mechanistically dissimilar interventions to each other and to existing monoaminergic treatments in MDD.” 
Currently, esketamine is FDA-approved for adults living with TRD. while psilocybin remains under clinical investigation in the United States.

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Results revealed that an oral 25-mg dose of psilocybin significantly reduced depressive symptoms 21 days after administration, with a Number Needed to Treat (NNT)— the number of patients needed to treat to prevent one bad outcome—of 5. Psilocybin-induced nausea was notable, with a Number Needed to Harm (NNH)—the number of patients that must receive a treatment for 1 additional patient to experience an adverse outcome—of 5 after day 1. This study set a value of <10 as clinically meaningful or efficacious.

Fixed-dose esketamine at 56-mg and 84-mg demonstrated efficacy at 28 days post-administration, with an NNT of 7. Esketamine-induced headache, nausea, dizziness, and dissociation, had NNHs of <10. 

Despite the promising results, the study authors acknowledged limitations, including that “the preliminary results may only reflect a small portion of the patient population” and that “these results require replication and longer-term studies investigating maintenance therapy.”

Nevertheless, these findings underscore the clinical relevance of esketamine and psilocybin as potential treatment options for adults with TRD. TRD affects about 30% of people diagnosed with major depressive disorder (MDD).1

With relatively few pharmacological agents proving effective in this population, the study provides valuable insights for practicing psychiatrists navigating treatment options for TRD patients, researchers concluded.

Reference

 

Wong S, Kwan ATH, Teopiz KM, et al. A comparison between psilocybin and esketamine in treatment-resistant depression using number needed to treat (NNT): A systematic review. J Affect Disord. 2024;350:698-705. doi:10.1016/j.jad.2024.01.142

1Johns Hopkins Medicine. Mood disorders: treatment-resistant depression. Accessed May 14, 2024.