The future of ketamine in psychiatry

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Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.1 NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.1 The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.1 Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

  • increased ictal time
  • augmented mid-ictal slow-wave amplitude
  • shortened post-treatment re-orientation time
  • less cognitive dysfunction.2

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.


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