Dosing and Pharmacokinetics of Ketamine

The dose and desired effects of ketamine greatly depends on the bioavailability of ketamine which is dependent on the route of administration.

Ketamine can be administered in the following ways:

  • Intravenous Infusion

  • Intramuscular Injection

  • Intranasal spray

  • Sublingual troche lozenge

  • Sublingual rapid dissolve tablet

  • Rectal suppository (PR)

  • Oral liquid tablets (PO) (Chong et al., 2009; Glue et al., 2021; Peltoniemi et al., 2016)

Video: Methods and Routes of Administration of Ketamine

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In this video, Dr. Reid provides some key considerations when selecting the methods and routes of administration. He also explains how bioavailability plays into treatment planning.

All of these methods use the racemic mixture of ketamine except the intranasal spray which can either be the racemic mixture or the S-(+) enantiomer which is branded as Spravato®.

Dose Quantities

Health professionals should be mindful of how the bioavailability of ketamine can vary significantly depending on the route of administration. Below are the recommended doses to achieve the desired effects.

Please ensure that you scroll all the way to the right to see the full content of the table before proceeding.

Bioavailability Peak Effect Dose Equivalent (0.5mg/kg IV in 70kg adult) Dose Equivalent (1mg/kg IV in 70kg adult)
IV infusion

100%

1 min

35mg

70mg
IM injection

93%

5 mins

33mg

75mg
Racemic intranasal spray

40-50%*

15 mins

~75mg

~150mg
Esketamine intranasal spray

40-50%*

(~1.8x)**

15 mins

~2 devices = 56mg

~3 devices - 84mg
Lozenge

25-40%*

20-30 mins

~100mg

~200mg
Rapid dissolve tablet

25-40%*

15-30 mins

~100mg

~200mg
PR suppository

25-40%*

20-45 mins

~100mg

~200mg
PO liquid

15-25%*

1-2 hours

~200mg

~400mg

Adapted from Chong et al., 2009; Glue et al., 2021; and Peltoniemi et al., 2016.

Note

Blood pressure should be monitored while the client is under the effects of ketamine, especially prior to providing an additional dose.

Ketamine as an Antidepressant

One strategy to prolong ketamine’s antidepressant response is to administer repeated IV doses (McMullen et al., 2021). Preliminary data suggests that the administration of both intramuscular and IV repeated doses of ketamine is safe and efficacious in treating depression (aan het Rot et al., 2010; Cusin et al., 2012). However, the need for maintenance in the pure IV model may relate to only harnessing the biological effect of the drug.

Thus, a different approach to prolonging ketamine’s effects, such as ketamine-assisted therapy, might be a more appropriate treatment rather than simply a pharmacological therapy (Greenway et al., 2020; Guidi & Fava, 2021; Hasler, 2020).

Video: What is Spravato?

m:ss

In this video, we will learn about the key differences between Spravato and generic ketamine and how these are used in ketamine therapy and ketamine-assisted therapy.

References

aan het Rot, M., Collins, K. A., Murrough, J. W., Perez, A. M., Reich, D. L., Charney, D. S., & Mathew, S. J. (2010). Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biol Psychiatry, 67(2), 139-145.

Chong, C., Schug, S. A., Page-Sharp, M., Jenkins, B., & Ilett, K. F. (2009). Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: Preliminary findings from a three-way randomized, crossover study. Clin Drug Investig, 29(5), 317-324. https://doi.org/10.2165/00044011-200929050-00004

Cusin, C., Hilton, G. Q., Nierenberg, A. A., & Fava, M. (2012). Long-term maintenance with intramuscular ketamine for treatment-resistant bipolar II depression. Am J Psychiatry, 169(8), 868-869. https://doi.org/10.1176/appi.ajp.2012.12020219

Glue, P., Russell, B., & Medlicott, N. J. (2021). Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Eur J Clin Pharmacol, 77(5), 671-676. https://doi.org/10.1007/s00228-020-03047-z

Greenway, K. T., Garel, N., Jerome, L., & Feduccia, A. A. (2020). Integrating psychotherapy and psychopharmacology: psychedelic-assisted psychotherapy and other combined treatments. Expert Rev Clin Pharmacol, 13(6), 655-670. https://doi.org/10.1080/17512433.2020.1772054

Guidi, J., & Fava, G. A. (2021). Sequential Combination of Pharmacotherapy and Psychotherapy in Major Depressive Disorder: A Systematic Review and Meta-analysis. JAMA Psychiatry, 78(3), 261-269. https://doi.org/10.1001/jamapsychiatry.2020.3650

Hasler, G. (2020). Toward specific ways to combine ketamine and psychotherapy in treating depression. CNS Spectr, 25(3), 445-447. https://doi.org/10.1017/S1092852919001007

McMullen, E. P., Lee, Y., Lipsitz, O., Lui, L. M. W., Vinberg, M., Ho, R., . . . McIntyre, R. S. (2021). Strategies to Prolong Ketamine's Efficacy in Adults with Treatment-Resistant Depression. Adv Ther, 38(6), 2795-2820. https://doi.org/10.1007/s12325-021-01732-8

Peltoniemi, M. A., Hagelberg, N. M., Olkkola, K. T., & Saari, T. I. (2016). Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet, 55(9), 1059-1077. https://doi.org/10.1007/s40262-016-0383-6