SUMMARY

PRODUCT LABELING

Clinical Studies

SPRAVATO Dose Distribution and Dosing Frequency in SUSTAIN-1 Study

In a phase 3, double-blind, active-controlled, multicenter, long-term, maintenance-of-effect study, starting from week 8, an algorithm (based on the Montgomery-Åsberg Depression Rating Scale [MADRS]) was used to determine the dosing frequency for SPRAVATO. Patients in remission (i.e., MADRS total score was ≤12) were dosed every other week; however, if the MADRS total score increased to >12, then the frequency was increased to weekly dosing for the next 4 weeks, with the objective of maintaining the patient on the lowest dosing frequency to maintain response/remission.¹

Of the patients randomized to SPRAVATO, 60.5% received 84 mg and 39.5% received 56 mg dose.^3,6 For dosing frequency, see Table: Dosing Frequency Used the Majority of Time During the Maintenance Phase.

In this study, 31.6% of patients received SPRAVATO for >6 months and 7.9% of patients received SPRAVATO for >1 year in the maintenance phase.³

SPRAVATO Dose Distribution and Dosing Frequency in SUSTAIN-2 Study

In a phase 3, open-label, multicenter, long-term, safety study, starting from week 9 to week 52 of the optimization/maintenance phase, SPRAVATO was administered either weekly or every other week depending on the MADRS score (every other week for MADRS total score of ≤12 and weekly for MADRS total score >12).² A dose increase was not permitted after week 8. If needed for tolerability, a dose reduction by 28 mg from the previous dose was permitted from week 9 through the end of the maintenance phase.^2,7

Of 603 patients in the optimization/maintenance phase (weeks 5-52), 24% of patients received weekly dosing, 38.1% were maintained on every-other-week dosing, and 37.8% switched back and forth between weekly and every-other-week dosing. The final SPRAVATO dose was 56 mg in 45.6%, 84 mg in 50.2%, and 28 mg in 4% of patients, and median SPRAVATO exposure was 22.9 weeks.²

Nijs et al (2020)⁸ conducted a post hoc analysis of SUSTAIN-2 to assess the effect of dosing frequency changes on efficacy assessed by Clinical Global Impression-Severity (CGIS) score. Patients worsening on every-other-week SPRAVATO dosing experienced better outcomes from weekly dosing. See Table: CGI-S Score After Change in Treatment Frequency. The authors note that the treatment protocol allowed changes in dosing frequency no more often than every 4 weeks, with a maximum of 3 changes; however, in clinical practice, they recommend a prompt increase in dosing frequency if a worsening of depressive symptoms is observed sooner than 4 weeks after switching from every week to every other week.

SPRAVATO Dose Distribution and Dosing Frequency in SUSTAIN-3 Study

In a phase 3, open-label extension study evaluating the long-term safety and efficacy of individualized, intermittently dosed SPRAVATO in patients with treatment-resistant depression (N=1148), median exposure to SPRAVATO was 45.8 months, with the duration of exposure ranging from ≥3 years (63% of patients) to ≥5 years (28% of patients); total exposure was 3777 cumulative patient-years. During the maintenance phase, SPRAVATO was most frequently administered weekly (approximately 40%-50% of patients), followed by every other week (approximately 35%-45% of patients), and every 4 weeks (approximately <10% to ~20% of patients by the end of study). The final SPRAVATO dose was 84 mg for most patients during induction (78.2%) and maintenance (64.4%).⁴

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) pertaining to this topic was conducted on 26 February 2024.