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The effect of intravenous, intranasal, and oral Psychedelic Therapy in mood disorders: A meta-analysis

Background: Psychedelic Therapy is established as a rapid and effective treatment in adults with treatment-resistant de-pression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes.

Methods: Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2–6 days, 7–20 days, 21–28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral
routes of administration. Analysis was also conducted evaluating the effect size of racemic Psychedelic Therapy to eske-tamine.

Results: The pooled effect size for intranasal Psychedelic Therapy/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591–1.903, p < 0.01). At 2–6 days, the pooled effect size for intravenous Psychedelic Therapy/esketamine was g = 0.949 (n = 14, 95% CI: −0.308–2.206, p = 0.139). At 7–20 days, intranasal Psychedelic Therapy had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499–1.538, p < 0.01). At 21–28 days, oral Psychedelic Therapy had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368–0.898, p < 0.01). Limitations: Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery.

Conclusions: The short-term efficacy of intravenous and intranasal Psychedelic Therapy/esketamine for adults with TRD was established. Interpreting the efficacy of oral Psychedelic Therapy was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD.

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