Copyright Notice This presentation is copyrighted by the Psychopharmacology Institute. Subscribers can download it and use it for professional use. The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

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

Ketamine NMDA receptor antagonist NMDA Olney JW, Newcomer JW, Farber NB (1999). NMDA receptor hypofunction model of schizophrenia. Journal of Psychiatric Research 33, 523-33.

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, 523-33.

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, 523-33.

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, 523-33.

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, 523-33.

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, 1459-72.

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, 1459-72.

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, 1459-72.

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, 1459-72.

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

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

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

Key Points Ketamine Fast but transient antidepressant response

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

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

Next Presentation: Psilocybin