SUMMARY

• Under the direct supervision of a healthcare provider, SPRAVATO is self-administered twice a week during weeks 1-4 in the induction phase, followed by maintenance treatment once weekly during weeks 5-8, and then every 2 weeks or once weekly from week 9 forward. Evidence of therapeutic benefit should be evaluated at the end of the induction phase to determine the need for continued treatment. Dosing frequency should be individualized to the least frequent dosing to maintain remission/response.^1,2
• In a long-term, event-driven, randomized withdrawal study (SUSTAIN-1), median exposure to SPRAVATO during the maintenance phase was 17.7 weeks among stable remitters and 19.4 weeks among stable responders.³
• In the open-label, long-term extension study that evaluated the safety and efficacy of SPRAVATO (SUSTAIN-3; N=1148), the median exposure to SPRAVATO was 45.8 months (range, 0-79 months); 728 (63.4%) and 322 (28.0%) patients were exposed to SPRAVATO for ≥3 years and ≥5 years, respectively. During the parent and SUSTAIN-3 studies combined, the cumulative duration of intermittent SPRAVATO treatment was ≥3 years in 777 (67.7%) patients and ≥5 years in 432 (37.6%) patients.⁴
• Clinical practice guidelines for major depressive disorder (MDD) recommend continued treatment with an antidepressant after an initial response.
  • Per the American Psychiatric Association Practice Guideline for the Treatment of Patients with Major Depressive Disorder (2010), continuation of pharmacotherapy is strongly recommended following successful acute phase antidepressant therapy, with a recommended duration of approximately 4-9 months (assuming good and consistent control of depression symptoms).⁵
    • For patients with additional risk factors for recurrence of MDD, such as the presence of residual symptoms, ongoing psychosocial stressors, family history of mood disorders, and the severity of prior episodes, maintenance therapy should be strongly considered.
    • Many patients (ie, chronic and recurrent MDD or co-occurring medical and/or psychiatric disorders) will require some form of maintenance treatment indefinitely.
  • Per the Department of Veterans Affairs/Department of Defense Clinical Practice Guidelines for the Management of Major Depressive Disorder (2022), patients should continue to take the medication even after feeling better. To decrease the risk of relapse in patients who achieve remission after a first episode of MDD, those patients are recommended to continue antidepressant treatment for at least 6 months. Patients who have had at least 2 episodes of MDD or at a high risk of relapse or recurrence are recommended to continue pharmacotherapy for at least 12 months and possibly indefinitely.⁶
• Two Delphi panel studies were conducted to obtain a consensus on the length of SPRAVATO treatment for patients with treatment-resistant depression (TRD).^7,8
  • In one study, 83% of panelists reached consensus to consider the severity of relapse consequences when determining the duration of SPRAVATO maintenance therapy.⁷
  • In the other study, 80% of panelists agreed that the minimum total treatment duration with SPRAVATO plus an oral antidepressant should be 6 months in patients with TRD.⁸

DELPHI PANEL STUDIES

A study was conducted to obtain expert clinical opinions on patient profiles and various clinical scenarios regarding the continuation or discontinuation of SPRAVATO treatment for patients with TRD, using a Delphi panel consisting of 30 psychiatrists and neurologists from 5 countries in Europe over 3 rounds.⁷

• The panel was asked questions about their caseload⁷:
  • On average, 55 patients managed by panelists had failed at least 2 antidepressant therapies in the past 3 months, including 23, 36, and 40 patients who had failed 2, 3, and ≥4 pharmacological antidepressant therapies, respectively.
  • Panelists prescribed SPRAVATO to 36% of patients they managed.
  • The average duration of SPRAVATO treatment for a patient experiencing benefit was 8 months.
  • During the acute phase of SPRAVATO treatment, patients achieved remission or a clinical response in an average of 7 weeks.
  • 32% of patients were receiving SPRAVATO as maintenance therapy for longer than 6 months following remission.
• The interim results from the first round are as follows⁷:
  • 83% of panelists reached consensus on early dose optimization of SPRAVATO to 84 mg to improve remission or achieve a stable response during the acute phase.
  • 83% of panelists reached consensus on prioritizing the monitoring of residual depressive symptoms to prevent relapse during the continuation phase.
  • 93% of panelists reached consensus on the use of nonpharmacological interventions, and 90% agreed on optimizing the SPRAVATO dose and frequency to sustain remission gains and/or symptomatic improvement during the continuation phase.
  • 83% of panelists reached consensus to consider the severity of relapse consequences (eg, loss of functioning, suicide attempts, inability to work) when determining the duration of SPRAVATO maintenance therapy.
  • 80% of panelists reached consensus on using augmentation strategies (including psychotherapy, mood stabilizers, anxiolytics, and antipsychotics) for patients who relapsed during SPRAVATO maintenance treatment.

Another study was conducted to obtain expert clinical opinion on the appropriate duration of SPRAVATO treatment for patients with TRD using a Delphi panel comprised of up to 11 psychiatrists from the United States, European Union, and United Kingdom.⁸

• 80% of panelists agreed that the minimum total treatment duration with SPRAVATO plus an oral antidepressant should be 6 months in patients with TRD.
• A consensus could not be obtained regarding the duration for continuing treatment in patients who achieved remission (modal response: 6-12 months; 50% agreement).
• 100% of panelists agreed that the minimum duration of maintenance treatment (ie, the phase of treatment that aims to prevent the onset of a new major depressive episode (recurrence) following recovery (the period when the current major depressive episode has ended based on clinical judgment and the patient has minimal to no depressive symptoms) of the current episode should be 6 months.
• A consensus could not be reached for the recommended maximum duration of maintenance treatment due to insufficient evidence (modal response: 24 months; 60% agreement).
• 80% of panelists agreed that the decision to discontinue SPRAVATO should be based on individual patient factors (eg, number and severity of prior depressive episodes and number of treatment failures) and according to clinical judgment.
• 80% of panelists also agreed that those who achieve recovery with SPRAVATO require maintenance treatment with oral antidepressants to prevent recurrence.

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 22 May 2025.