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SPRAVATO® (esketamine)

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SPRAVATO - Medications Used to Treat Depression Prior to Randomization or Study Entry into Phase 3 Trials

Last Updated: 01/17/2025

SUMMARY

Venlafaxine was the most common antidepressant used prior to randomization or study entry across the majority of the phase 3 studies in patients with treatment-resistant depression (TRD) and major depressive disorder (MDD) with active suicidal ideation and intent. Many classes of antidepressants are represented in the tables below, including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), serotonin modulators, and miscellaneous antidepressants (ie, bupropion and mirtazapine). Other medication classes include adjunctive treatments such as atypical antipsychotics and mood stabilizers.¹^-⁷
- Studies in TRD - Antidepressants and Other Drugs for Treatment of Depression Utilized by ≥5% of Patients in Any Treatment Arm Prior to Randomization or Study Entry
- Studies in MDD and Active Suicidal Ideation with Intent - Antidepressants and Other Drugs for Treatment of Depression Utilized by ≥5% of Patients in Either Treatment Arm Prior to Study Entry

CLINICAL DATA

The following tables list, by study, the antidepressants used by ≥5% of patients in any treatment arm prior to randomization or study entry.

Studies in TRD - Antidepressants and Other Drugs for Treatment of Depression Utilized by ≥5% of Patients in Any Treatment Arm Prior to Randomization or Study Entry^a,b

TRANSFORM-1¹	TRANSFORM-2²	TRANSFORM-3³	SUSTAIN-1⁴	SUSTAIN-2⁵
Venlafaxine Bupropion Escitalopram Fluoxetine Sertraline Duloxetine Citalopram Paroxetine Mirtazapine Vortioxetine Aripiprazole Quetiapine Trazodone Desvenlafaxine Lamotrigine Clomipramine Levomilnacipran Vilazodone Nortriptyline	Venlafaxine Sertraline Escitalopram Bupropion Fluoxetine Duloxetine Mirtazapine Citalopram Trazodone Paroxetine Vortioxetine Quetiapine Aripiprazole Desvenlafaxine Lamotrigine Amitriptyline Clomipramine Olanzapine Nortriptyline Lithium	Mirtazapine Sertraline Venlafaxine Bupropion Duloxetine Citalopram Escitalopram Fluoxetine Paroxetine Vortioxetine Clomipramine Quetiapine Trazodone Aripiprazole Desvenlafaxine Fluvoxamine	Venlafaxine Escitalopram Sertraline Bupropion Mirtazapine Duloxetine Vortioxetine Fluoxetine Aripiprazole Trazodone Citalopram Paroxetine Clomipramine Lamotrigine Mianserin (not available in the US)	Venlafaxine Sertraline Escitalopram Mirtazapine Duloxetine Fluoxetine Paroxetine Bupropion Quetiapine Vortioxetine Aripiprazole Citalopram Trazodone Desvenlafaxine Amitriptyline Clomipramine
Abbreviations: TRD, treatment-resistant depression; US, United States. ^aMedications are listed, by study, in the order of the most commonly used in the total population. ^bBenzodiazepines are excluded. Note: Patients were only required to fail the oral antidepressants in these lists (≥2 oral antidepressants in the current depressive episode) in order to be eligible for study entry or randomization in phase 3 trials.⁸^-¹²

Although they did not meet the above threshold (≥5% of patients in any treatment arm), monoamine oxidase inhibitors (MAOIs) were also listed among the antidepressants used prior to randomization or study entry. Those MAOIs included tranylcypromine, isocarboxazid, selegiline, and phenelzine.¹^-⁵

Studies in MDD and Active Suicidal Ideation with Intent - Antidepressants and Other Drugs for Treatment of Depression Utilized by ≥5% of Patients in Either Treatment Arm Prior to Study Entry^a,b

ASPIRE-1⁶	ASPIRE -II⁷
Escitalopram Venlafaxine Mirtazapine Duloxetine Trazodone Bupropion Sertraline Paroxetine Fluoxetine Desvenlafaxine Agomelatine Quetiapine Aripiprazole Olanzapine Lamotrigine Gabapentin	Venlafaxine Escitalopram Duloxetine Trazodone Sertraline Fluoxetine Mirtazapine Bupropion Desvenlafaxine Vortioxetine Clomipramine Quetiapine Olanzapine Aripiprazole Lithium Gabapentin
Abbreviations: MDD, major depressive disorder. ^aMedications are listed, by study, in the order of the most commonly used in the total population. ^bBenzodiazepines are excluded.

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 16 December 2024.

References

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1	Data on File. Esketamine. Clinical Study Report ESKETINTRD3001. Janssen Research & Development, LLC. EDMS-ERI-144473122; 2018.
2	Data on File. Esketamine. TRANSFORM-2 Clinical Study Report ESKETINTRD3002. Janssen Research & Development, LLC. EDMS-ERI-139094789; 2018.
3	Data on File. Esketamine. Clinical Study Report ESKETINTRD3005. Janssen Research & Development, LLC. EDMS-ERI-144748748; 2018.
4	Data on File. Esketamine. SUSTAIN-1 Clinical Study Report ESKETINTRD3003. Janssen Research & Development, LLC. EDMS-ERI-149282394; 2018.
5	Data on File. Esketamine. Clinical Study Report ESKETINTRD3004. Janssen Research & Development, LLC. EDMS-ERI-146551506; 2018.
6	Data on File. Esketamine. Clinical Study Report 54135419SUI3001. Janssen Research & Development, LLC. EDMS-ERI-187180494; 2019.
7	Data on File. Esketamine. Clinical Study Report 54135419SUI3002. Janssen Research & Development, LLC. EDMS-ERI-180130932; 2019.
8	Ochs-Ross R, Daly EJ, Zhang Y, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28(2):121-141.
9	Popova V, Daly EJ, Trivedi M, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176(6):428-438.
10	Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22(10):616-630.
11	Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891.
12	Daly EJ, Trivedi MH, Janik A, et al. Supplement to: Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019;76(9):893-903.