SUMMARY  

• A subgroup analysis of a phase 3, open-label, long-term extension study (SUSTAIN-3) evaluated the safety and efficacy of SPRAVATO by dosing frequency in patients with treatment-resistant depression (TRD).¹
  • The study consisted of a 4-week induction phase and an optimization/maintenance (OP/M) phase of variable duration. Patients were able to enroll in the induction phase or the OP/M phase based on their status from the end of the previous trial.
  • During the maintenance phase, the dosing frequency could be adjusted per protocol to weekly, every other week, or every 4 weeks based on the Clinical Global Impressions-Severity (CGI-S) score.
  • Mean Montgomery–Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) total scores remained stable over the treatment course for all dosing frequency groups, with no new safety signals identified.
• There is no information on every 3-week dosing or dosing intervals greater than every 4 weeks.

CLINICAL DATA

Zajecka et al (2024)¹ conducted a subgroup analysis of a phase 3, open-label, long-term extension study (SUSTAIN-3) evaluating the safety (up to 6.5 years) and efficacy of SPRAVATO by dosing frequency in patients with TRD. The study design consisted of a 4-week induction phase followed by an OP/M phase of variable duration. Patients entered the study from 1 of 6 phase 3 trials conducted previously, including TRANSFORM-1, TRANSFORM-2, TRANSFORM-3, SUSTAIN-1, SUSTAIN-2, and TRD-3006 (US only). Patients were able to enroll in the induction phase or the OP/M phase based on their status from the end of the previous trial.

During the induction phase, patients received SPRAVATO at doses of 28 mg (age ≥65), 56 mg, or 84 mg twice weekly. Starting at week 4, dosing frequency was adjusted based on the CGI-S score. See Table: Algorithm for Adjusting Treatment Session Frequency (if applicable) Starting Week 4. Starting at week 5, investigators were allowed to adjust dose based on patient tolerability and efficacy.

Results

For baseline and clinical characteristics of the subgroups, see Table: Baseline and Clinical Characteristics by Mode Dosing Frequency. Of the 1097 patients included in the analysis in the OP/M phase, the dosing frequency for 591 (54%) patients was weekly; 369 (34%) patients, every other week; and 137 (12%) patients, every 4 weeks.

For the dosage and duration of treatment with SPRAVATO by dosing frequency in the OP/M phase, see Table: Duration and Dose of SPRAVATO in the OP/M Phase by Mode Dosing Frequency and Figure: Distribution of SPRAVATO Dosing Frequency Over Time Starting From Week 4 of the OP/M Phase.

Efficacy

The mean (standard deviation [SD]) change in MADRS and PHQ-9 total scores from the baseline of the OP/M phase to the end of the study (312 weeks) based on the last-observation-carried-forward (LOCF) for a mode dosing frequency of weekly were 2.0 (10.4) and 1.5 (6.6); every other week, -1.8 (8.7) and -0.3 (5.4); and every 4 weeks, -2.2 (9.8) and -0.8 (6.2), respectively. See Figures: Mean MADRS Total Score Over Time by Mode Dosing Frequency and Mean PHQ-9 Total Score Over Time by Mode Dosing Frequency. The proportion of patients in remission (defined by a MADRS total score of ≤12) based on LOCF data for weekly dosing was 24.7%; every other week, 75.6%; and every 4 weeks, 88.3%.

Safety

The most common TEAEs were headache, nausea, dizziness, nasopharyngitis, dissociation, and dysgeusia (see Table: Most Common TEAEs [≥10%] by Mode Dosing Frequency).

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 17 January 2025.