Summary

• Across the SPRAVATO phase 3 studies in treatment-resistant depression, patients receiving psychotherapy before entering the trials (including cognitive behavioral therapy [CBT]) could continue receiving psychotherapy during the trials.¹
  • CBT must have been ongoing for the last 3 months prior to the screening/prospective, observational phase. Except for new CBT, which was prohibited, new psychotherapy was allowed during these studies.¹
  • During the phase 3 program, one study removed the restriction related to CBT and allowed for all previous forms of psychotherapy to be continued or newly initiated during the study.²
• The clinical trial program in major depressive disorder with suicidal ideation and intent provided all patients with standard-of-care (SOC) treatment, which may have included psychotherapy.³
  • In the ASPIRE-II trial, 5.3% (6/115) of patients in the SPRAVATO+SOC group and 4.4% (5/115) of patients in the placebo+SOC group received psychotherapy during the double-blind treatment phase.

CLINICAL DATA

Gutiérrez-Rojas et al (2025)⁴conducted a retrospective, observational, multicentric study to assess the effectiveness and tolerability of SPRAVATO in patients with treatment-resistant depression (TRD) in a compassionate use program in Spain. Efficacy of treatment was assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment.

• 71 patients (women, 70%; mean age, 54.6) were enrolled with a mean baseline MADRS score of 38.3 ± 5.9.
• Concomitant antidepressant medications included SSRIs (38%), SNRIs (63.4%), TCAs and MAOIs (57.7%), mood stabilizers (32.4%), and atypical antipsychotics (46.5%).
• 46.5% of the patients also received cognitive behavioral therapy (not SPRAVATO-assisted CBT).
• Clinical response to SPRAVATO was observed by a significant reduction in MADRS total score (P≤0.0001 at all timepoints) from baseline (38.3 ± 5.9) at 28 days (23.4 ± 12.9), 90 days (16.9 ± 11.2), and 180 days (14.1 ± 11.5).
• CBT was significantly associated with lower MADRS scores after 90 days (13.1 vs 16.1; P=0.021) and 180 days of treatment (12.3 vs 16.1; P=0.021) compared with those who did not receive CBT.
• Overall, ≥95% of patients experienced an adverse event, with the most frequently reported being dissociation (56.3%), dizziness (36.6%), sedation (31.0%), drowsiness (28.2%), and paresthesia (28.2%). Adverse events were not analyzed for the SPRAVATO + CBT cohort.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 18 August 2025.