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Dosage and Administration of SPRAVATO - Duration of Therapy

Last Updated: 07/06/2023


  • SPRAVATO should be administered in conjunction with an oral antidepressant in adults with treatment-resistant depression (TRD). 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 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 an ongoing, open-label, long-term, extension study evaluating the safety (primary) and efficacy (secondary) of SPRAVATO (SUSTAIN-3), the median exposure to SPRAVATO was 31.7 months (35.8 months including exposure in the preceding parent study), while 35 patients were on SPRAVATO for ≥48 months.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
  • A 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.
    • 80% of panelists agreed that the minimum total treatment duration with SPRAVATO plus an oral antidepressant should be 6 months in patients with TRD.7
    • 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 (i.e., 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 (e.g., 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 04 July 2023.


1 Center for Drug Evaluation and Research. Summary Review. NDA 211243 - SPRAVATO (esketamine) - Reference ID: 4398871. Published July 5, 2019. Accessed July 06, 2023.
2 Center for Drug Evaluation and Research. Clinical Pharmacology and Biopharmaceutics Review. NDA 211243 - SPRAVATO (esketamine) - Reference ID: 4398871. Published July 5, 2019. Accessed July 06, 2023.
3 Daly EJ,  Singh JB,  Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: results of a double-blind, doubly-randomized, placebo-controlled study. JAMA Psychiatry. 2018;75(2):139-148.
4 Zaki N,  Nash A,  Chen N, et al. Long-term safety of esketamine nasal spray in patients with treatment-resistant depression: interim results of the SUSTAIN-3 study. Poster presented at: Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP); June 2, 2021; Virtual Meeting.
5 Work Group on Major Depressive Disorder, Gelenberg, A.J., Freeman, M.P., et al. Practice Guideline for the Treatment of Patients With Major Depressive Disorder. 3rd. Washington, DC: American Psychiatric Association; 2010.
6 Department of Veterans Affairs and the Department of Defense. VA/DoD clinical practice guideline for the management of major depressive disorder, version 4.0. Published April 2022. Accessed July 06, 2023.
7 Nash AI ,  Borenstein S,  O'Hara M, et al. Treatment-resistant depression: expert consensus identified real-world experience and individualized care as considerations for novel treatments in major depressive disorder. National Network of Depression Centers (NNDC); September 21-22, 2021; Virtual Meeting.