SPRAVATO® esketamine nasal spray adult patient
SPRAVATO® esketamine nasal spray adult patient
Actor portrayal.
Gradient

TRD Efficacy & Safety

Over 60,000 patients in the US have received treatment with SPRAVATO®. Learn more about the recent data and results from the short-term and long-term studies below.1

TRD=treatment-resistant depression in adults (for patients with MDD who have had an inadequate response to 2 or more oral ADs).

Demonstrated rapid and superior improvement in depressive symptoms at Week 4 compared to placebo + oral AD2,3

TRANSFORM-1 (Short-term)

Time course of treatment response chart with results of SPRAVATO® + oral AD versus placebo nasal spray + oral ADTime course of treatment response chart with results of SPRAVATO® + oral AD versus placebo nasal spray + oral AD
  • Most of the treatment difference between SPRAVATO® and placebo was observed at 24 hours
  • Between 24 hours and Day 28, both SPRAVATO® and placebo groups continued to improve, and the difference between these 2 groups generally remained the same

AD=antidepressant.

LS=least squares.

MADRS=Montgomery-Åsberg Depression Rating Scale.

Click here to see short-term safety data

TRD Study 1 (Short-term) study design2,3

Evaluated in a randomized, placebo-controlled, double-blind, short-term (4-week) study in adults with TRD; all patients in the trial received a new oral AD. Primary endpoint was change from baseline in the MADRS total score at 4 weeks.2,3

Demonstrated superior improvement in depression symptoms at Week 4 for adults with TRD2,3

TRD Study 1 short-term study design overview of SPRAVATO® + new oral AD and placebo nasal spray + new oral AD

Other Secondary Descriptive Endpoints

  • Response at Week 4
  • Remission at Week 4

Flexible Dosing

  • Patients (aged 18-64 years) were randomized to receive twice-weekly doses of SPRAVATO® (flexible dose; 56 mg or 84 mg) plus a newly initiated oral AD or intranasal placebo plus newly initiated oral AD
  • Dosages could be titrated to 84 mg or maintained on 56 mg, and were adjusted on Day 4, 8, 11, or 15
  • Dosages remained stable after Day 15

Oral Antidepressant

  • A newly initiated open-label oral AD (SSRIs: escitalopram, sertraline; SNRIs: duloxetine, venlafaxine extended-release) was initiated on Day 1
  • The selection of the newly initiated oral AD was determined by the investigator based on patient’s prior history

Demographics and Baseline Characteristics

  • Median age 47 years; 62% female; 93% Caucasian; 5% Black

SNRI=serotonin and norepinephrine reuptake inhibitor.

SSRI=selective serotonin reuptake inhibitor.

Key secondary efficacy results3,4
  • 7.9% of patients receiving SPRAVATO® + oral AD achieved response by Day 2 and maintained response by Day 28 vs 4.6% with placebo + oral AD
    • The difference was not statistically significant
  • Mean total SDS score change with SPRAVATO® + oral AD was -13.6 vs -9.4 with placebo + oral AD by Day 28
  • Mean total PHQ-9 score change with SPRAVATO® + oral AD was -13.0 vs -10.2 with placebo + oral AD by Day 28

*Response was defined as ≥50% improvement in MADRS total score by Day 2 that continued through to the end of the double-blind treatment phase, with 1 excursion allowed.

Given the lack of statistical significance on the first secondary endpoint, analyses of the other 2 key secondary endpoints could not be formally evaluated.†

†The 3 key secondary endpoints were analyzed sequentially and were considered significant at the 2-sided, 0.05 level only if the individual and previous endpoints in the hierarchy, including the primary endpoint, were significant.

AD=antidepressant.

MADRS=Montgomery-Åsberg Depression Rating Scale.

PHQ-9=Patient Health Questionnaire-9 (used specifically for depression).

SDS=Sheehan Disability Scale.

Secondary descriptive endpoints:
  • At Week 4, 52.5% of patients receiving SPRAVATO® + oral AD achieved remission vs 31.0% with placebo + oral AD

TRD Study 1 (Short-term)

Two bar graphs comparison of secondary descriptive endpoints between response rates at week 4 versus remission rates at week 4
  • Response was defined as an improvement of at least 50% from baseline in total MADRS score
  • Remission was defined as a MADRS total score of ≤12
  • All subjects taking SPRAVATO® started on 56 mg on Day 1. Dose adjustment was made on prespecified days based on clinical judgment
Short-term studies:
TRD safety and tolerability of SPRAVATO®

SPRAVATO® plus oral antidepressant offers your patients a consistent safety profile with a minimal risk for sexual dysfunction compared to placebo + oral antidepressant2,5

  • Sexual dysfunction was not observed in SPRAVATO® trials at a rate greater than 2%

TRD=treatment-resistant depression in adults (for patients with MDD who have had an inadequate response to 2 or more oral ADs).

Adverse events chart of SPRAVATO® + oral AD versus placebo + oral AD

Most TEAEs (93.7%) occurred and resolved on the same day of dosing6

In a 4-week study, the majority of dissociation (98.3%), blood pressure increase (86.4%), and sedation (83.3%) occurred and resolved on the same day of dosing6

*The following terms were combined:

Dissociation includes: delusional perception; depersonalization/derealization disorder; derealization; diplopia; dissociation; dysesthesia; feeling cold; feeling hot; feeling of body temperature change; hallucination; hallucination, auditory; hallucination, visual; hyperacusis; illusion; ocular discomfort; oral dysesthesia; paresthesia; paresthesia oral; pharyngeal paresthesia; photophobia; time perception altered; tinnitus; vision blurred; visual impairment

Dizziness includes: dizziness; dizziness exertional; dizziness postural; procedural dizziness

Sedation includes: altered state of consciousness; hypersomnia; sedation; somnolence

Vertigo includes: vertigo; vertigo positional

Hypoesthesia includes: hypoesthesia; hypoesthesia oral, hypoesthesia teeth, pharyngeal hypoesthesia

Anxiety includes: agitation; anticipatory anxiety; anxiety; fear; feeling jittery; irritability; nervousness; panic attack;tension

Lethargy includes: fatigue; lethargy

Blood pressure increased includes: blood pressure diastolic increased; blood pressure increased; blood pressure systolic increased; hypertension

Headache includes: headache; sinus headache

Dysgeusia includes: dysgeusia; hypogeusia

Nasal discomfort includes: nasal crusting; nasal discomfort; nasal dryness; nasal pruritus

Dysarthria includes: dysarthria; slow speech; speech disorder

Tachycardia includes: extrasystoles; heart rate increased; tachycardia

AD=antidepressant.

TEAEs=treatment-emergent adverse effects.

Click here to see long-term efficacy data
You can have the confidence that SPRAVATO® demonstrated low discontinuation rates:
4.6% of patients taking SPRAVATO® discontinued treatment due to adverse events

*Two short-term TRD studies in adults <65 years.

SPRAVATO® is administered at certified treatment centers.

Find a Center

Safety Considerations2

Click to expand each SPRAVATO® safety consideration below

Contraindications iconContraindications
Emergency iconSuicidal Thoughts and Behaviors in Young Adults
Sedation iconSedation
Blood pressure iconBlood Pressure
Timer iconDissociation
Cognitive iconCognitive Impairment
Lungs iconRespiratory Depression
No driving iconImpaired Ability to Drive and Operate Heavy Machinery
Abuse iconAbuse and Misuse
Ulcerative or Interstitial Cystitis iconUlcerative or Interstitial Cystitis
REMs iconREMS
People iconUse in Specific Populations
Pill iconDrug Interactions

References:

  1. 1.Data on File. Janssen Pharmaceuticals, Inc.

  2. 2.SPRAVATO® [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

  3. 3.Popova V, Daly E, 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. doi:10.1176/appi.ajp.2019.19020172

  4. 4.Popova V, Daly E, 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)(Suppl). https://ajp.psychiatryonline.org/doi/suppl/10.1176/appi.ajp.2019.19020172/suppl_file/appi.ajp.2019.19020172.ds001.pdf

  5. 5. Data on File. Janssen Pharmaceuticals, Inc.

  6. 6. Data on File. Janssen Pharmaceuticals, Inc.

  7. 7.Zaki N, Fu DJ, Daly E, et al. Long-term safety of esketamine nasal spray in adults with treatment-resistant depression: a subgroup analysis of the ongoing SUSTAIN-3 study. Poster presented at: Neuroscience Education Institute (NEI) Congress; November 4-7, 2021; Colorado Springs, CO.

Safety results from the long-term SUSTAIN-3 trial up to 5+ years were consistent with the safety and tolerability profile established in the pivotal trials3

During the combined Induction and Optimization/Maintenance phases, 967 patients (94.7%) experienced a treatment-emergent adverse event (TEAE)3

IND Phase=56 mg or 84 mg — twice weekly.

OP/M Phase=56 mg or 84 mg — flexibly dosed.*

*Based on CGI-S and tolerability.

Percentages of TRD long-term study results TEAEs table
Additional 5+ year safety results3
  • A total of 184 patients (18.0%) experienced serious TEAEs; serious TEAEs occurring in >5 patients included depression (n=16), suicide attempt (n=15), suicidal ideation (n=9), and COVID-19 (n=7)
  • Six deaths (0.6%) related to TEAEs occurred; investigator assessment determined none were considered to be related to SPRAVATO®
You can have the confidence that SPRAVATO® demonstrated low discontinuation rates:
4-week and 6-year TRD study percentages of patients taking SPRAVATO® who discontinued treatment due to adverse events

*Two short-term TRD studies in adults aged <65 years.

†Median duration of exposure to SPRAVATO® was 46.9 months (range, 0-79).

IND=Induction.

OP/M=Optimization/Maintenance.

TRD 5+ year MADRS Results & PHQ-9 Scores

TRD=treatment-resistant depression in adults (for patients with MDD who have had an inadequate response to 2 or more oral ADs).

In a long-term, open-label safety study, MADRS and PHQ-9 scores were consistent throughout analyses of the final data over 5.1 years3

Mean MADRS Total Scores (Observed Cases) during the induction and optimization/maintenance phases over 5 years

6.5-year safety trial was composed of 2 phases: a 4-week IND phase and a variable duration OP/M phase.2

  • Of the 1021 patients studied in this cohort, 50% were treated with SPRAVATO® for at least 46.9 months
    • Patients eligible for this subgroup analysis were 18-64 years of age and received SPRAVATO® 56 mg or 84 mg twice weekly during IND phase and flexible dosing during OP/M phase; all patients should have taken a permitted oral AD for the duration of the study

BL=baseline.

MADRS=Montgomery-Åsberg Depression Rating Scale.

PHQ-9=Patient Health Questionnaire-9 (used specifically for depression).

In a long-term, open-label safety study, MADRS and PHQ-9 scores were consistent throughout analyses of the final data over 5.1 years3

Mean PHQ-9 Total Scores (Observed Cases) during the induction and optimization/maintenance phases over 5 years

Mean change from baseline in the PHQ-9 total scores (observed cases) showed an improvement over the 4-week IND phase.

This improvement appeared to be maintained with flexibility dosed SPRAVATO® over the OP/M phase.

BL=baseline.

LOCF=last observation carried forward.

PHQ-9=Patient Health Questionnaire-9 (used specifically for depression).

TRD long-term safety extension study3

The following data is drawn from a Phase 3, open-label, long-term safety extension study in adults with treatment-resistant depression (TRD).

Limitations:

  • Results from an open-label, long-term safety study with no comparator group. Efficacy data not assessed for statistical significance
  • This is a subgroup analysis of the study population and there are low n sizes beyond 5.1 years that limit the generalizability of the results
  • Generalizability of study findings may be limited by patients who chose to continue from the parent study and by exclusion of participants with significant comorbidities (psychiatric or medical, or substance dependence)

Study Design2,3

A subgroup analysis was conducted on a cohort of 1,021 patients who met criteria consistent with the on-label population. Of the total patients, 440 (43.1%) entered the study at the Induction (IND) phase and 581 (56.9%) entered at the Optimization/Maintenance (OP/M) phase.

  • Patients eligible for this subgroup analysis were 18-64 years of age and received SPRAVATO® 56 mg or 84 mg twice weekly during the IND phase and flexible dosing during the OP/M phase; all patients should have taken a permitted oral AD for the duration of the study
TRD Study 2 (long-term) of SPRAVATO® + oral AD versus placebo + oral AD over 80 weeksTRD Study 2 (long-term) of SPRAVATO® + oral AD versus placebo + oral AD over 80 weeks

Primary objective: Characterize the long-term safety

IND Phase=56 mg or 84 mg – twice weekly.

OP/M Phase=56 mg or 84 mg – flexibly dosed.*

Based on CGI-S and tolerability.

AD=antidepressant.

CGI-S=Clinical Global Impressions-Severity scale.

IND=Induction.

OP/M=Optimization/Maintenance.

Maintenance-of-effect study

In a separate long-term maintenance-of-effect trial, patients in stable remission were less likely to relapse* when they continued SPRAVATO® vs those who discontinued and were switched to placebo5,6

SUSTAIN-1 (Long-term)

TRD Study 2 (long-term) of SPRAVATO® + oral AD versus placebo + oral AD over 80 weeks
  • Stable remission was defined as a MADRS total score of ≤12 in at least 3 of the last 4 weeks of the optimization phase

Relapse was defined as a MADRS total score of ≥22 for 2 consecutive weeks and/or hospitalization for worsening depression, or any other clinically relevant event determined per clinical judgment to be suggestive of a relapse of depressive illness.

AD=antidepressant.

MADRS=Montgomery-Åsberg Depression Rating Scale.

SUSTAIN-1 (Long-term) study design5,6

Evaluated in a long-term, randomized, double-blind, parallel-group, variable duration study in adults who were known remitters and responders. Primary endpoint was time to relapse in patients in stable remission.4,5

Significantly delayed time to relapse in a long-term maintenance trial in adults with TRD with stable remission4,5

TRD Study 2 (Long-term) study design overview of SPRAVATO® + oral AD and placebo nasal spray + oral ADTRD Study 2 (Long-term) study design overview of SPRAVATO® + oral AD and placebo nasal spray + oral AD

Enrollment

  • 437 patients (aged 18-64 years) were directly enrolled
    • Patients who were directly enrolled received SPRAVATO® (56 mg or 84 mg twice/week) plus a new oral AD in a 4-week open-label induction phase before entering a 12-week optimization phase
  • 268 patients (aged 18-64 years) were transferred from short-term studies

Demographics and Baseline Characteristics

  • Median age 48 years (range 19-64 years); 66% female; 90% Caucasian; 4% Black

SPRAVATO® is administered at certified treatment centers.

Find a Center

References:

  1. 1.Data on File. Janssen Pharmaceuticals, Inc.

  2. 2.Zaki N, Fu DJ, Daly E, et al. Long-term safety of esketamine nasal spray in adults with treatment-resistant depression: a subgroup analysis of the ongoing SUSTAIN-3 study. Poster presented at: Neuroscience Education Institute (NEI) Congress; November 4-7, 2021; Colorado Springs, CO.

  3. 3.Zajecka J, Zaki N, Fu D et al. Long-term efficacy of esketamine nasal spray dosed in accordance with US prescribing information in adults with treatment-resistant depression: a subgroup analysis of the SUSTAIN-3 study up to 6.5 years. Poster presented at: Psych Congress; September 6-10, 2023; Nashville, TN.

  4. 4. Data on File. Janssen Pharmaceuticals, Inc.

  5. 5.SPRAVATO® [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

  6. 6.Daly E, Trivedi M, Janik A, et al. Efficacy of esketamine nasal spray plus an oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2019; 76(9):893-903.

ESCAPE-TRD efficacy: primary endpoint

Patients with treatment-resistant depression (TRD) on SPRAVATO® were 65% more likely to achieve remission at Week 8 compared to
QUE XR2

SPRAVATO® vs QUE XR Primary Endpoint: Rates of Remission at Week 82,3

Graph of percentages of patients achieving remission in head-to-head study of SPRAVATO® + oral AD and QUE XR + oral AD

Remission was defined as MADRS total score ≤10.

(Remission was defined as MADRS ≤12 in SPRAVATO® pivotal data. Using this definition of remission, the remission rate at Week 8 was 40.4% for SPRAVATO® and 24.4% for QUE XR.)

CI=confidence interval.

OR=odds ratio.

QUE XR=quetiapine extended release.

No definitive conclusions can be made of superiority between treatments. Subanalysis efficacy data not assessed for statistical significance.

ESCAPE-TRD efficacy: secondary endpoint

55.7% of patients who received SPRAVATO® + oral AD were in remission at Week 32 compared to 36.3% who received QUE XR + oral AD2

Remission Over Time

Graph of percentages week-by-week remission rates of patients over 32 weeksGraph of percentages week-by-week remission rates of patients over 32 weeks

Remission was defined as MADRS total score ≤10.

(Remission was defined as MADRS ≤12 in SPRAVATO® pivotal data.)

LOCF=last observation carried forward.

OAD=oral antidepressant.

QUE XR=quetiapine extended release.

Response Over Time

3 out of 4 (75.9%) patients treated with SPRAVATO® + oral AD achieved response compared to ~2 out of 4 (55.0%) treated with QUE XR + oral AD at Week 32

Graph of percentages week-by-week response rates of patients over 32 weeks

Response at a given time point was defined as ≥50% improvement in MADRS total score from baseline or MADRS total score ≤10.

LOCF=last observation carried forward.

OAD=oral antidepressant.

QUE XR=quetiapine extended release.

No definitive conclusions can be made of superiority between treatments. Subanalysis efficacy data not assessed for statistical significance.

Safety Considerations

SPRAVATO® offers an established and consistent safety profile2,3

TEAEs2,3

Table of most common Treatment-emergent adverse events (TEAEs) compared between head-to-head SPRAVATO® + oral AD and QUE XR + oral AD
  • Safety set: all randomized patients who took ≥1 dose of treatment

*Occurring in ≥10% of patients in either study arm.

QUE XR=quetiapine extended release.

TEAE=treatment-emergent adverse event.

Discontinuation rates

SPRAVATO® discontinuation rates from the head-to-head study were consistent with previous studies in TRD

4.4% patients taking SPRAVATO® discontinued treatment due to adverse events10.6% of patients taking QUE XR discontinued treatment due to adverse events

QUE XR=quetiapine extended release.

Study design2

The following data is drawn from a head-to-head subanalysis of a study in adults with treatment-resistant depression (TRD)

Limitations:

  • This is a subanalysis of only one study and is not adjusted for multiplicity; no definitive superiority conclusions can be made between treatments
  • The study had an open-label design. A common concern is that the patients’ knowledge of treatment received might influence their view/reporting of their symptoms
  • Participants in the SPRAVATO® arm had twice-weekly visits with drug administration under supervision of an HCP for the first 4 weeks of the study; during the same time period, participants in the quetiapine extended-release (QUE XR) arm were seen once weekly
    • Differences in the frequency of study visits between groups, treatment compliance, and routes of administration could potentially introduce bias into the results
  • While inclusion was based on DSM-5 criteria for MDD, the study was conducted in an ex-US patient population and cannot unequivocally be extrapolated to a US population

Study Design2,3

  • This is a head-to-head, open-label, rater-blinded, randomized study
  • A subanalysis was conducted on a cohort of 636 adults with TRD who met criteria consistent with the US registration and labeling
    • Only patients who received dosing consistent with the US label, SPRAVATO® 56 mg or SPRAVATO® 84 mg, and <65 years of age (94% of the total study population from the original European regulatory study) were included in this analysis.
TRD Study 2 (long-term) of SPRAVATO® + oral AD versus placebo + oral AD over 80 weeksTRD Study 2 (long-term) of SPRAVATO® + oral AD versus placebo + oral AD over 80 weeks

Demographics and Baseline Characteristics2:

  • SPRAVATO® + oral AD: Mean age 42.8 years; 67.1% female
  • QUE XR + oral AD: Mean age 44.5 years; 64.7% female

*Assessed using last observation carried forward approach.

AD=antidepressant.

MADRS=Montgomery-Asberg Depression Rating Scale.

MDD=major depressive disorder.

QUE XR=quetiapine extended release.

SPRAVATO® is administered at certified treatment centers.

Find a Center

References:

  1. 1.Data on File. Janssen Pharmaceuticals, Inc.

  2. 2.Godinov Y, Buyze J, Turkoz I, et al. Esketamine nasal spray versus quetiapine extended release in patients with treatment-resistant depression: a subgroup analysis of the ESCAPE-TRD Study. Poster presented at: American Association of Psychiatric Pharmacists (AAPP); April 16-19, 2023; Atlanta, GA.

  3. 3.SPRAVATO® [Prescribing Information]. Titusville, NJ: Janssen Pharmaceuticals, Inc.

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