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2. Ketamine for TRD Prof. Philip Cowen Professor of Psychopharmacology
Department of Psychiatry
University of Oxford, UK

3. Ketamine NMDA receptor antagonist NMDA
Olney JW, Newcomer JW, Farber NB (1999). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research 33,

4. Ketamine NMDA receptor antagonist General dissociative anesthetic NMDA
Olney JW, Newcomer JW, Farber NB (1999). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research 33,

5. Ketamine NMDA receptor antagonist General dissociative anesthetic
Pharmacological model of schizophrenia
Olney JW, Newcomer JW, Farber NB (1999). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research 33,

6. Ketamine NMDA receptor antagonist General dissociative anesthetic
Pharmacological model of schizophrenia
Transient symptoms of psychosis and cognitive impairment
Olney JW, Newcomer JW, Farber NB (1999). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research 33,

7. Ketamine NMDA receptor antagonist General dissociative anesthetic
Pharmacological model of schizophrenia
Transient symptoms of psychosis and cognitive impairment
NMDA receptor hypofunction hypothesis of schizophrenia
Olney JW, Newcomer JW, Farber NB (1999). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research 33,

8. Ketamine for TRD Amelioration of depressive symptoms
Sub-anesthetic doses: 0.5 mg/kg
Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU (2016). Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychological Medicine 46,

9. Ketamine for TRD Effects emerge as dissociative effects wane
Amelioration of depressive symptoms
Sub-anesthetic doses: 0.5 mg/kg
Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU (2016). Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychological Medicine 46,

10. Ketamine for TRD Effects emerge as dissociative effects wane
Amelioration of depressive symptoms
40 mins post-injection
Sub-anesthetic doses: 0.5 mg/kg
Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU (2016). Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychological Medicine 46,

11. Ketamine for TRD 30% to 40% of patients: effects last for several days
Effects emerge as dissociative effects wane
Amelioration of depressive symptoms
40 mins post-injection
Sub-anesthetic doses: 0.5 mg/kg
Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU (2016). Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories. Psychological Medicine 46,

12. Ketamine: future treatments
Intranasal ketamine
Administered on a sub-chronic basis

13. Ketamine: future treatments
Intranasal ketamine
Administered on a sub-chronic basis
Will effects be long term?
Tolerance or adverse effects?

14. Ketamine: future treatments
Intranasal ketamine
Administered on a sub-chronic basis
Will effects be long term?
Tolerance or adverse effects?
Understanding MOA of ketamine to develop new drugs

15. Key Points
Ketamine
Fast but transient antidepressant response

16. Key Points Ketamine Fast but transient antidepressant response
New forms are being studied in clinical trials

17. Key Points Ketamine Fast but transient antidepressant response
New forms are being studied in clinical trials
MOA is being explored: role of hydroxy- metabolite

18. Next Presentation: Psilocybin