Contraindications

Here are general contraindications to therapeutic ketamine, followed by potential medication interaction contraindications:

General Contraindications:

• Uncontrolled cardiovascular disease like hypertension [1]
• History of psychosis or bipolar I disorder [2]
• Brain tumor, aneurysm, or seizure disorder [3]
• Allergy or hypersensitivity to ketamine [4]
• Hepatic insufficiency [5]
• Pregnancy and breastfeeding [6]

Medication Interactions:

• Sympathomimetics (may enhance cardiovascular effects) [7]
• Amantadine (may prolong dissociative effects) [8]
• Theophylline (cardiovascular effects) [9]
• Haloperidol (cardiovascular effects) [10]
• Lithium (increased neurotoxicity) [11]
• Propofol (cardiorespiratory depression) [12]
• Benzodiazepines (additive sedation) [13]
• Opioids (additive respiratory depression) [14]

Careful monitoring is required when ketamine is used with the above agents. Dose adjustments may be warranted to mitigate risks.

Serotonin Syndrome

Very little on it, but in a singular case study, it was correlated with concurrent administration of fluoxetine. Extremely rare, but be aware of this medication’s contraindications.

“For Ms. O, we suspected that administering ketamine in conjunction with fluoxetine, 40 mg/d, led to serotonin syndrome. “

• Contraindication

The concurrent use of cocaine and ketamine can also potentially cause it.

Lamictal and Risperidone

Both potentially reduce the effectiveness of ketamine, according to this study: Ketamine and other depression meds.

Gabapentin

Ketamine operates against the GABA receptors, as does Gabapentin, so there is an overlap that could conflict. Many reports almost no reaction to ketamine when taking Gabapentin.

Grapefruit Juice

There are reported interactions (as is familiar with grapefruit juice and other meds), but the exact effect caused is unclear.

Liver Interaction

• Rifampin, a tuberculosis drug that decreases ketamine
• St John’s Wort is a popular supplement for various conditions that reduces ketamine.
• Ketoconazole, an anti-fungal medication that increases ketamine
• Cimetidine (Tagamet), an acid reducer for heartburn and peptic ulcers that theoretically increases ketamine
• Orphenadrine (Norflex), a muscle relaxant, inhibits CYP2B6 and slows the breakdown of ketamine which increases the amount of ketamine in the body
• Dexamethasone, a common steroid, actually induces CYP2B6 and speeds up the breakdown of ketamine. This decreases the amount of ketamine left in your system to work

References:

[1] Pai A, Heining M. Ketamine. [Updated 2022 Feb 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482377/

[2] DeWilde KE, Levitch CF, Murrough JW, Mathew SJ, Iosifescu DV. The Promise of Ketamine for Treatment-Resistant Depression: Current Evidence and Future Directions. Ann N Y Acad Sci. 2015;1345:47-58. doi:10.1111/nyas.12747

[3] Short B, Fong J, Galvez V, Shelker W, Loo CK. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry. 2018;5(1):65-78. doi:10.1016/S2215-0366(17)30272-9

[4] Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113(3):678-684. doi:10.1097/ALN.0b013e3181ed09a2

[5] Morgan CJ, Curran HV; Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction. 2012;107(1):27-38. doi:10.1111/j.1360-0443.2011.03576.x

[6] Mitra S, Mahintamani T, Kavoor AR, Nizamie SH. Negative impact of ketamine abuse on urinary, sexual, emotional functions and menstrual cycle in women: A cross-sectional study. Ind Psychiatry J. 2016;25(2):182-186. doi:10.4103/ipj.ipj_45_16

[7] White PF, Way WL, Trevor AJ. Ketamine–its pharmacology and therapeutic uses. Anesthesiology. 1982;56(2):119-136. doi:10.1097/00000542-198202000-00024

[8] Ohashi K, Sato S, Tashiro C, et al. Interaction of ketamine and amantadine in healthy volunteers. Acta Anaesthesiol Scand. 2012;56(5):623-630. doi:10.1111/j.1399-6576.2011.02646.x

[9] White PF. Comparative evaluation of intravenous agents for rapid sequence induction–thiopental, ketamine, and midazolam. Anesthesiol Rev. 1982;9(11):35-40.

[10] White PF, Way WL, Trevor AJ. Ketamine–its pharmacology and therapeutic uses. Anesthesiology. 1982;56(2):119-136. doi:10.1097/00000542-198202000-00024

[11] White PF, Schüttler J, Shafer A, Stanski DR, Horai Y, Trevor AJ. Comparative pharmacology of the ketamine isomers. Studies in volunteers. Br J Anaesth. 1985;57(2):197-203. doi:10.1093/bja/57.2.197

[12] Wehner M, Mamach M, Obara I, et al. Ketamine and Propofol Do Not Interact Adversely During Simultaneous Administration. Anesth Analg. 2019;128(5):1053-1060. doi:10.1213/ANE.0000000000004072

[13] White PF. Comparative evaluation of intravenous agents for rapid sequence induction–thiopental, ketamine, and midazolam. Anesthesiol Rev. 1982;9(11):35-40.

[14] Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014;77(2):357-367. doi:10.1111/bcp.12094