SUMMARY

• Phase 3 clinical trials of SPRAVATO in patients with treatment-resistant depression (TRD)^1-4 excluded patients who were nonresponsive to an adequate course of electroconvulsive therapy (ECT) in the current major depressive episode, defined as ≥7 treatments with unilateral/bilateral ECT.^5-8
• Phase 3 clinical trials of SPRAVATO in patients with moderate to severe major depressive disorder and active suicidal ideation with intent,^9,10 allowed for the inclusion of ECT non-responders at imminent risk for suicide.^11,12 However, no subgroup analyses were performed to assess efficacy or safety in these patients.
• A real-world, prospective study in Spain evaluating the effectiveness, tolerability, and safety of SPRAVATO in 16 patients with TRD, including 6 with prior ECT, reported no significant differences in Montgomery-Åsberg depression rating scale (MADRS) scores between those who received prior ECT and those who did not.¹³
• A real-world, retrospective study in Israel evaluating the effectiveness of SPRAVATO in 62 adult patients with TRD, including 15 with prior ECT, reported that significantly more patients with prior ECT responded to treatment with SPRAVATO vs patients without prior ECT during the acute phase (8 weeks) of treatment (P<0.05).¹⁴

Clinical Data

Real-world Studies

Vendrell-Serres et al (2024)¹³ conducted a single-center, real-world, prospective study in Spain from February 2020 to November 2022 to evaluate the effectiveness, tolerability, and safety of SPRAVATO in adult patients with TRD enrolled in an expanded use program prior to commercial availability of SPRAVATO. To be eligible for treatment, patients were required to have failed ≥2 oral antidepressants during the current episode, ≥1 combination/augmentation treatment, and have refused or failed ≥1 nonpharmacological treatment, such as ECT. The study also explored the effect of prior ECT on treatment response.

Study Design/Methods

• SPRAVATO (dose range, 28 mg to 84 mg) was administered twice-weekly in the 4-week induction phase, followed by once-weekly to every 2 weeks in the 6-month maintenance phase, based on individual clinical response and tolerability. The follow-up period was up to 4 months.
• Depressive symptoms using the MADRS were assessed at baseline (T1), and after 48 hours (T2), 8 days (T3), 15 days (T4), 22 days (T5), 29 days (T6), 2 months (T7), 3 months (T8), and 4 months (T9).
• Response was defined as ≥50% reduction in the baseline MADRS score, and remission was defined as a MADRS score of ≤12.

Results

• 16 patients were included (mean age, 53.1 years; age range, 27 to 71 years; female, 56.3%; mean baseline MADRS score, 36.7), of which 6 (37.5%) were treated with prior ECT.
• The mean MADRS scores at T1, T6, and T9 were 26.7, 19.1, and 16.0, respectively (P<0.00001).
• At the end of the induction phase, 50.5% of patients responded, while 31.3% remitted at the end of the study.
• Mixed model analysis of the influence of prior ECT on MADRS scores reported no significant differences between patients who previously received ECT and those who did not (coefficient, -1.75; confidence interval [CI], -6.88 to 3.37; P=0.503).
• Two patients discontinued treatment prematurely due to a worsening of depressive symptoms.
• Adverse events (AEs) included dissociation (37.5%), sleepiness (25.0%), nausea (18.8%), anxiety (12.5%), blurry vision, paresthesia, high blood pressure and headache, and metallic taste (6.25% each).
• All AEs were mild and did not require treatment, except for 1 moderate case of high blood pressure and headache, which was treated with captopril 25 mg.
• No AEs were specified for the group of patients who had prior ECT.

Dvorak et al (2024)¹⁴ conducted a single-center, real-world, retrospective study in Israel from January 2021 to January 2023 to evaluate the effectiveness of SPRAVATO in adult patients with TRD, including the influence of prior ECT on SPRAVATO treatment.

Study Design/Methods

• The recommended dosing of SPRAVATO was administered twice weekly during the first 4-8 weeks of treatment, followed by weekly in the maintenance phase for 4 weeks, and then continued once every two weeks for at least 6 months.
• Assessments were made using the Quick Inventory of Depressive Symptomatology (QIDS) score at baseline, weekly during the acute phase, and monthly during the maintenance phase (4-6 months).
• In the acute phase, response was defined as a 30% improvement in the baseline QIDS score; partial response, a 9-30% improvement; nonresponse, a <9% improvement.
• In the maintenance phase, response was defined as >45% improvement in the baseline QIDS score; partial response, 25-45% improvement; nonresponse, <25% improvement.

Results

• 62 patients were included (mean age, 43.2 years; female, 54.1%), in which 15 received prior ECT.
• In the acute phase, 22 patients (35.5%) were responders, 17 patients (27.4%) were partial responders, and 23 patients (37.1%) were non-responders.
• In the maintenance phase, 17 patients (51.5%) were responders, 11 patients (33.3%) were partial responders, and 5 patients (15.2%) were non-responders; 33 patients completed the maintenance phase.
• QIDS scores significantly decreased from the baseline in the acute and maintenance phases (baseline, 22.73±4.8; acute phase, 16.55±6.5; and maintenance phase, 12.15±6.37; P<0.001).
• During the acute phase, significantly more patients with prior ECT responded to treatment with SPRAVATO vs patients without prior ECT (53.3% vs 31.8%; P<0.05).

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 31 January 2025.

This response excludes case reports.^15-20