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Actor portrayal.

About SPRAVATO® for
Treatment-Resistant Depression (TRD)

SPRAVATO® patients’ stories

Indications

SPRAVATO® is for use alone or in combination with an oral antidepressant for:

  • Adults with treatment-resistant depression (MDD patients who have had an inadequate response to 2 or more oral ADs)

SPRAVATO® is for use in combination with an oral antidepressant for:

  • Depressive symptoms in adults with MDD with acute suicidal ideation or behavior (MDSI)

Limitations of Use:

  • The effectiveness of SPRAVATO® in preventing suicide or in reducing suicidal ideation or behavior has not been demonstrated. Use of SPRAVATO® does not preclude the need for hospitalization if clinically warranted, even if patients experience improvement after an initial dose of SPRAVATO®.
  • SPRAVATO® is not approved as an anesthetic agent. The safety and effectiveness of SPRAVATO® as an anesthetic agent have not been established.

AD=antidepressant.

MDD=major depressive disorder.

SPRAVATO® (esketamine) Prescription Nasal Spray device
SPRAVATO® (esketamine) Prescription Nasal Spray device

How SPRAVATO® Works

SPRAVATO® is different because it targets glutamate, the most abundant excitatory neurotransmitter in the brain

The primary antidepressant activity of SPRAVATO® is not believed to directly involve inhibition of serotonin or norepinephrine reuptake.

The precise mechanism of action (MOA) is unknown.1,3-6

SPRAVATO® is an NMDA receptor antagonist. An NMDA receptor is an ionotropic glutamate receptor.1

NMDA=N-methyl-D-aspartate.

SPRAVATO® hypothesized MOA.

SPRAVATO® hypothesized MOA infographic
  • Clinical study results suggest that glutamate transmission is abnormally regulated in multiple areas of the brain of individuals with depression7,8
  • Antagonism of the NMDA receptor and AMPA receptor activation leads to downstream release of BDNF and activation of kinases9-11
  • BDNF expression and downstream signaling are thought to enhance neurogenesis and mediation of synaptic excitability and plasticity11,12
  • It is important to note that the relationship between this pathway and the clinical effects of depression have not been established

AMPA=α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.

BDNF=brain-derived neurotrophic factor.

How SPRAVATO® nasal spray works

When oral ADs have your patients going in circles,
it’s time for a different approach

After inadequate response to at least 2 oral ADs for MDD, the same treatment modality may not be enough

  • Oral ADs don’t work for everyone
    • - Patients are highly unlikely to achieve remission on the third line of treatment4*
  • Patients cycling through current oral medications may wait 4-6 weeks for potential relief 5
STAR*D trial: third-line treatment graphic
STAR*D trial: third-line treatment graphic

Real Stories of SPRAVATO® Patients and Caregivers

Share these stories with your patients. To learn more about these patients’ experiences with SPRAVATO®, click here.

“When I was truly in my throes of depression, I would start every day off at like a negative six versus a zero. After I started taking SPRAVATO®, I’m starting off the day waking up neutral, which is the best.”

Nicole P., St. Peters, Missouri

Nicole, 23,* is a real patient with treatment-resistant depression and has been compensated for her time and testimonial by Johnson & Johnson.

*Testimonial filmed in 2018.
Individual results may vary.

“My son is 22* now and he’s doing so much better.”

Allison F., Pikeville, Kentucky Caregiver for son with treatment-resistant depression

Allison is a real caregiver for her adult son with treatment-resistant depression. She is an employee of Janssen Pharmaceuticals Companies of Johnson & Johnson.

*Testimonial filmed in 2021. Individual results may vary.

“I am in a better place than I have been — maybe ever. I think that’s an amazing gift.”

Grace K., Colorado Springs, Colorado

Grace, 29,* is a real patient with treatment-resistant depression and has been compensated for her time and testimonial by Johnson & Johnson

*Testimonial filmed in 2021. Individual results may vary.

References:

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

2. A study of esketamine nasal spray, administered as monotherapy, in adult participants with treatment-resistant depression. ClinicalTrials.gov identifier: NCT04599855. Accessed January 19, 2025. https://clinicaltrials.gov/study/NCT03170518

3. Duman R, Aghajanian G, Sanacora G, et al. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22(3):238-249. doi:10.1038/nm.4050

4. Duman R, Li N, Liu RJ, et al. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 2012;62(1):35-41 doi:10.1016/j.neuropharm.2011.08.044

5. Sanacora G, Zarate C, Krystal J, et al. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7(5):426-437. doi:10.1038/nrd2462

6. Sanacora G, Zarate C, Krystal J, et al. Neuropharmacology. 2012;62(1):63-77. doi:10.1016/j.neuropharm.2011.07.036

7. Zarate C, Machado-Vieira R, Henter I, et al. Harv Rev Psychiatry. 2010;18(5):293-303. doi:10.3109/10673229.2010.511059

8. Musazzi L, Treccani G, Mallei A, et al. Biol Psychiatry. 2013;73(12):1180-1188. doi:10.1016/j.biopsych.2012.11.009

9.Serafini G, Gonda X, Rihmer Z, et al. Ann Clin Psychiatry. 2015;27:213-220.

10. Miladinovic T, Nashed MG, Singh G, et al. Biomolecules. 2015;5(4):3112-3141. doi:10.3390/biom5043112

11. Swanson CJ, Bures M, Johnson MP, et al. Nat Rev Drug Discov. 2005;4:131-144. doi:10.1038/nrd1630

12. Wang J, Jing L, Toledo-Salas JC, et al. Neurosci Bull. 2015;31(1):75-86. doi:10.1007/s12264-014-1484-6

13. Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one of several treatment steps: a STAR*D report. Am J Psychiatry. 2006;163(11):1905-1917. doi:10.1176/ajp.2006.163.11.1905

14. Practice guideline for the treatment of patients with major depressive disorder (revision). American Psychiatric Association. Am J Psychiatry. 2010:1-152.

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