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Ketamine: Current Applications for Compounding

If we were to list the most important health crises affecting the world today, the opioid epidemic and refractory depression would be at the top of our list. Ketamine could be part of the answer to both of these issues taking lives and devastating families. Pavilion Compounding Pharmacy has used ketamine to help patients with neuropathic pain and depression for years. Yet have we fully realized its potential? Thanks to recent research, many health care providers are now using this anesthetic to reduce opiate use for patients with both acute and chronic pain and to help people with depression. Pavilion Compounding Pharmacy has been compounding ketamine in various dosage forms over the past 20 years.

ACUTE AND CHRONIC PAIN

This year, the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists published joint guidelines on the use of ketamine infusions for acute pain management.1 The guidelines discuss sub-anesthetic use of ketamine as an IV dosage form as well as oral and nasal dosage forms. With this knowledge, ketamine may be an option in the acute-care setting to provide safe alternatives to opioids. Ketamine may also reduce opioid related side effects. It demonstrates fewer incidents of depressed respiration, cardiovascular function, hepatic blood flow and bowel function compared to opioids.1,2,3,4

In the chronic pain setting, ketamine can also play a role. In one randomized trial, patients with chronic neuropathic pain divided into three groups, one receiving ketamine, one receiving methadone and one receiving both. The ketamine group experienced greater pain relief after three months of therapy than the other groups.5 For patients with chronic neuropathic pain, the oral route offers a more patient-friendly option, as nasal sprays and sublingual dosage forms are bitter.

SEVERE DEPRESSION

Maybe the most exciting new discovery is ketamine’s usefulness for patients with severe depression. Roughly one-third of patients with major depressive disorder do not respond to currently approved antidepressants.6 The patients who do respond will have to wait sometimes months to see a full response to the medication. This leaves a large hole in the treatment of a disease that affects 16 million Americans.7

We do not fully understand the mechanism of ketamine’s action for depression, but we do know that it is multifactorial.8,9,10 Although a complicated process, the effects of ketamine are rapid and — for some patients with major, refractory depression — more effective than other medications. In these instances, ketamine is commonly prescribed as a nasal spray or a sublingual dosage form.

EXAMPLE FORMULAS

• Ketamine Sublingual Troche (10-200mg)

• Ketamine Nasal Spray (50-200 mg/mL)

As you can see, ketamine continues to be a drug with new answers to medical dilemmas. Pavilion Compounding Pharmacy is here to help you and your practitioners find those answers.

References 1. Schwenk, E. S., Viscusi, E. R., Buvanendran, A., Hurley, R. W., Wasan, A. D., Narouze, S., … Cohen, S. P. (2018). Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia & Pain Medicine, 43(5), 456–466. doi:10.1097/ AAP.0000000000000806

2. Pourmand, A., Mazer-Amirshahi, M., Royall, C., Alhawas, R., & Shesser, R. (2017). Low dose ketamine use in the emergency department, a new direction in pain management. The American Journal of Emergency Medicine, 35(6), 918–921. https://doi.org/10.1016/j.ajem.2017.03.005

3. Kurdi, M. S., Theerth, K. A., & Deva, R. S. (2014). Ketamine: Current applications in anesthesia, pain, and critical care. Anesthesia Essays and Researches, 8(3), 283–290. https://dx.doi.org/10.4103%2F0259-1162.143110

4. Thomson, I. A., Fitch, W., Campbell, D., & Watson, R. (1988). Effects of ketamine on liver blood flow and hepatic oxygen consumption. Studies in the anaesthetised greyhound. Acta Anaesthesiologica Scandinavica, 32(1), 10–14. https://doi.org/10.1111/j.1399-6576.1988.tb02677.

5. Rigo, F. K., Trevisan, G., Godoy, M. C., Rossato, M. F., Dalmolin, G. D., Silva, M. A., … Ferreira, J. (2017). Management of neuropathic chronic pain with methadone combined with ketamine: A randomized, double blind, activecontrolled clinical trial. Pain Physician, 20(3), 207–215. Retrieved from http:// www.painphysicianjournal.com/

6. Ionescu, D. F., Rosenbaum, J. F., & Alpert, J. E. (2015). Pharmacological approaches to the challenge of treatment-resistant depression. Dialogues in Clinical Neuroscience, 17(2), 111–126. Retrieved from https://www.ncbi.nlm. nih.gov/pmc/articles/PMC4518696/pdf/DialoguesClinNeurosci-17-111.pdf

7. National Institute of Mental Health. (2017). Major depression. Retrieved from https://www.nimh.nih.gov/health/statistics/major-depression.shtml

8. Choi, M., Lee, S. H., Park, M. H., Kim, Y. S., & Son, H. (2017). Ketamine induces brain-derived neurotrophic factor expression via phosphorylation of histone deacetylase 5 in rats. Biochemical and Biophysical Research Communications, 489(4), 420–425. https://doi.org/10.1016/j.bbrc.2017.05.157

9. Zhu, X., Ye, G., Wang, Z., Luo, J., & Hao, X. (2017). Sub-anesthetic doses of ketamine exert antidepressant-like effects and upregulate the expression of glutamate transporters in the hippocampus of rats. Neuroscience Letters, 639, 132–137. https://doi.org/10.1016/j.neulet.2016.12.070

10. Wang, N., Yu, H. Y., Shen, X. F., Gao, Z. Q. Yang, C., Yang, J. J., & Zhang, G. F. (2015). The rapid antidepressant effect of ketamine in rats is associated with down-regulation of pro-inflammatory cytokines in the hippocampus, Upsala Journal of Medical Scien

11. Tricia Heitman, PharmD, PCCA Clinical Compounding Pharmacist Nov2018 Apothagram

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