Spravato - Klaudia Stajka

1
New Hope for Depression
Name Surname
Klaudia Stajka (MD. ).
2
Outline

• Definition of Depression
• Symptoms of the disease
• Pathophysiology
• New drug discovered
• Mechanism of action
• Pharmacokinetics and Pharmacodynamics
• Side effects
• Conclusion
• References

Name Surname
3
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. (2,3,4,5)
•  

Name Surname
4
Symptoms

• Depressed mood
• Loss of pleasure (anhedonia)
• Significant weight change
• Sleep disturbance
• Psychomotor agitation or retardation
• Fatigue
• Feelings of worthlessness
• Diminished ability to think
• Recurrent thoughts of death

Name Surname
5
Pathophysiology
Name Surname
This picture is adapted from McCance Huether
(2014).
6
Ketamine Special K Mechanism of action
Name Surname
This photo is adapted from Duman RS.
F1000Research 2018, 7659
7
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
8
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.

Name Surname
9
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 dose is excreted as unchanged
  drug in urine.

Name Surname
10
Pharmacodynamics

• Cardiac Electrophysiology
• A large increase in heart rate (i.e. gt10 bpm) is
  observed in intranasal and intravenous esketamine
  treatment groups.
• Evidence (nonclinical and clinical data)
  indicates a lack of clinically relevant QTc
  prolongation.

Name Surname
11
Side effects

• Dissociation
• Dizziness
• Nausea
• Sedation
• Vertigo
• Hypoesthesia
• Anxiety
• Lethargy
• Blood pressure increased
• Vomiting

Name Surname
12
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, such
  as suicide.
• Hope has never been higher in medical community.

Name Surname
13

• Thank you for your attention!
• Klaudia Stajka (MD. ).

Name Surname
14
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) 61727.  5. Kessler RC The costs of
depression. Psychiatr Clin North Am. 2012 35(1)
114. Murray CJ, Atkinson C, Bhalla K, et al.
The state of US health, 19902010 burden of
diseases, injuries, and risk factors. JAMA. 2013 
310(6) 591608. 6. Duman RS. Ketamine and
rapid-acting antidepressants a new era in the
battle against depression and suicide. F1000Resear
ch. 20187F1000 Faculty Rev-659.
doi10.12688/f1000research.14344.1. 7. Dubovsky
SL. What Is New about New Antidepressants? Psychot
herapy and Psychosomatics. 201887(3)129-139.
doi10.1159/000488945. 8. SPRAVATO Prescribing
Information. Titusville, N.J., Janssen
Pharmaceuticals, Inc. 9. Thase ME. Update on
partial response in depression. J Clin
Psychiatry. 200970suppl 64-9. 10. Duman RS,
Li N (2012). A neurotrophic hypothesis 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 20724638  
Name Surname