Rather than inhibiting serotonin, noradrenaline and dopamine as do current antidepressants, ketamine is a non-competitive NMDA (N-methyl-D-aspartate) antagonist. Its effect on glutamate enhances α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor throughput relative to NMDA in critical neuronal circuits, offering new insights into the mechanisms involved in depression.
Animal studies show that ketamine reverses the atrophy of parts of the brain which is observed in depression, and promotes the growth of new nerve projections and synapses.
Ketamine is a short acting injectable anaesthetic which is useful as the sole anaesthetic agent for procedures that don’t need skeletal muscle relaxation, as an induction agent prior to other general anaesthetics, or as a supplement to low-potency agents, such as nitrous oxide.
Paramedics use it because the airway reflexes and respiratory drive are preserved, and there is minimal haemodynamic compromise. Disassociation, hallucinations, and the changed perception of reality also make it a popular party drug.
The Black Dog Institute is currently collaborating with the University of Adelaide and the University of Otago in the first Australian trial to investigate ketamine for depression.