Spravato - Klaudia Stajka
                     New Hope for Depression
Name Surname:
Klaudia Stajka (MD. ).
Outline 
• Definition of Depression 
• Symptoms of the disease
• Pathophysiology 
• New drug discovered 
•    Mechanism of action
•    Pharmacokinetics and Pharmacodynamics
•    Side effects 
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•    Conclusion 
•    References 
Depression
• Depression (MDD) – a serious medical illness that negatively affects 
how you feel, the way you think and how you act.
• MDD affects nearly 20% of the population at some point during the 
life span.
• It is estimated to be the number one cause of disability by 2020. 
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(2,3,4,5)
 
Symptoms 
• Depressed mood
• Loss of pleasure (anhedonia)
• Significant weight change 
• Sleep disturbance 
• Psychomotor agitation or retardation
• Fatigue 
• Feelings of worthlessness
• Diminished abilitNya mteo S utrhnaimnek:
• Recurrent thoughts of death
Pathophysiology 
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This picture is adapted from McCance & Huether (2014).
Ketamine – “Special  K”
Mechanism of action
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This photo is adapted from Duman RS. F1000Research 2018, 7:659 
Spravato- Esketamine CIII
•   Brand name: SPRAVATO.
•   Generic name: Esketamine. 
•   Approved by FDA on 5 March 2019.
•   Janssen Pharmaceutical Companies of Johnson & Johnson.
•   First major advance in depression drugs.
•   Uses the first new mechanism of action in 30 years, to treat MDD 
and TRD. (6,7) Name Surname:
Esketamine chemical structure
Mechanism of action
•   Esketamine - antagonist of the NMDA receptor.
•   The mechanism of action -  unknown. 
  •   It is different from current therapies.
•   Noresketamine demonstrated activity at the same receptor with 
less affinity. 
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Pharmacokinetics 
•  Administered as a nasal spray.
• Absorbed by the lining of the nasal passages into the blood stream (8). 
• Protein binding of esketamine -  43% to 45%.
• Esketamine - metabolized to Noresketamine metabolite via P450 (CYP) 
enzymes (CYP2B6, CYP3A4, CYP2C9 and CYP2C19). 
• Noresketamine - metabolized via CYP-dependent pathways.
• Less than 1% of a doNasmee  Siusr neamxec:reted as unchanged drug in urine. 
Pharmacodynamics 
Cardiac Electrophysiology 
•  A large increase in heart rate (i.e. >10 bpm) is observed in intranasal 
and intravenous esketamine treatment groups. 
•  Evidence (nonclinical and clinical data) indicates a lack of clinically 
relevant QTc prolongNaamtieo Sunrn.ame:
Side effects
•  Dissociation •  Lethargy
•  Dizziness •  Blood pressure increased
•  Nausea •  Vomiting
•  Sedation
•  Vertigo
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•  Hypoesthesia
•  Anxiety
Conclusion
•  SPRAVATOTM is the newest prescription medicine for Depression in 
adults.
•  Offers new hope to people with MDD and TRD who have not 
responded to existing therapies.(9)
•  70% of patient feel ease of symptoms in one day and potentially 
avoid self-injury, suNcahm ea Ssur nsaumei:cide.
• Hope has never been higher in medical community. 
Thank you for your attention!
Klaudia Stajka (MD. ).
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References 
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5), Fifth edition. 2013.
2. Garcia-Arocena, D. (n.d.). Happy or SAD: The chemistry behind depression. Retrieved October 29, 2018.
3. WHO: WHO | Depression [Internet]. Depression. 2017.
4. Kessler RC, Chiu WT, Demler O, et al.: Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National 
Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6): 617–27. 
5. Kessler RC: The costs of depression. Psychiatr Clin North Am. 2012; 35(1): 1–14. Murray CJ, Atkinson C, Bhalla K, et al.: The 
state of US health, 1990–2010: burden of diseases, injuries, and risk factors. JAMA. 2013; 310(6): 591–608.
6. Duman RS. Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide. F1000Research. 
2018;7:F1000 Faculty Rev-659. doi:10.12688/f1000research.14344.1.
7. Dubovsky SL. What Is New about New Antidepressants? Psychotherapy and Psychosomatics. 2018;87(3):129-139. 
doi:10.1159/000488945.
8. SPRAVATO™ [Prescribing Information]. Titusville, N.J., Janssen Pharmaceuticals, Inc.
9. Thase ME. Update on partial response in depression. J Clin Psychiatry. 2009;70[suppl 6]:4-9.
10. Duman RS, & Li N (2012). A neurotNroapmheic S huyrpnoatmhes: is of depression: role of synaptogenesis in the actions of NMDA receptor 
antagonists. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 367 (1601), 2475-84 PMID: 
22826346 
11. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, & Duman RS (2010). mTOR-dependent synapse 
formation underlies the rapid antidepressant effects of NMDA antagonists. Science (New York, N.Y.), 329 (5994), 959-64 PMID: 
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