By Rajnish Mago, MD (bio)
Question from a Member:
Are there any risks of a patient being on ketamine and stimulants simultaneously?
Questions about what to do about concomitant medications come up in almost every patient who receives ketamine treatment. Surprisingly, though the American Psychiatric Association’s Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders (Sanacora et al., 2017) urges review of concomitant medications, it offers no guidance on what to do about various concomitant medications.
My recommendations on this topic are based on the limited published literature, a review of the exclusion criteria of clinical trials of ketamine or esketamine for mood disorders, and my discussions with clinicians experienced in providing treatment with intravenous ketamine. This page will be updated as more information becomes available. Clinicians who administer the ketamine/ esketamine typically have protocols that they follow and advise patients about what to do about the concomitant medications.
Not a contraindication
Being on a stimulant medication is not a contraindication to receiving ketamine/ esketamine treatment. In clinical trials of intravenous ketamine or esketamine, being on a stimulant did not exclude patients for participating (e.g., Ionescu et al., 2019; Grunebaum et al., 2018; Grunebaum et al., 2017).
Blood pressure may increase
Ketamine/ esketamine can lead to a temporary increase in blood pressure immediately after they are administered even in patients who are not on a stimulant.
If the patient is on a stimulant, the increase in blood pressure may be greater. For example, the esketamine Prescribing Information notes: “Concomitant use with psychostimulants (e.g., amphetamines, methylphenidate, modafinil, armodafinil) may increase blood pressure. Closely monitor blood pressure with concomitant use of SPRAVATO with psychostimulants.”
So, we need to think about and monitor the blood pressure, especially in patients who are on a stimulant.
Before starting treatment
The temporary increase in blood pressure that often occurs after ketamine/ esketamine are given may, obviously, be more of a problem if the baseline blood pressure before treatment is already high since it may become even higher each time ketamine/ esketamine is given. So, the patient’s blood pressure should be checked as soon as ketamine/ esketamine are being considered. If it is high, attempts should be made to manage that even before the ketamine/esketamine treatment starts and continuing during the course of treatment.
On that day
The good news is that the increase in blood pressure related to administration of ketamine/ esketamine is temporary. The Prescribing Information for ketamine, which is used as an anesthetic in doses higher than those used for the treatment of major depression or bipolar depression, states: “Elevation of blood pressure begins shortly after injection, reaches a maximum within a few minutes and usually returns to preanesthetic values within 15 minutes after injection. In the majority of cases, the systolic and diastolic blood pressure peaks from 10% to 50% above preanesthetic levels shortly after induction of anesthesia, but the elevation can be higher or longer in individual cases.”
This means that the problem of an additive increase in blood pressure from ketamine/ esketamine is usually present only during and immediately after the treatment. So, for patients who are on a stimulant medication and need to continue it, a sufficient precaution may be to ask them to just not take the stimulant on the morning of the ketamine/ esketamine administration. Many leading ketamine treatment centers follow this practice.
After administration of ketamine/ esketamine
The problem is that if a patient has been on a stimulant and the stimulant is abruptly stopped, the patient may feel extremely tired. This happened to one of my patients who had been on methylphenidate extended-release for a while and was asked to not take the methylphenidate on days when she received intravenous ketamine.
In such situations, if needed, the patient could take a shorter-acting stimulant later in the day (a couple of hours after administration of ketamine/ esketamine) if blood pressure is normal.
If needed, patients on long-acting stimulants can be changed to shorter-acting preparations for the entire duration of ketamine/ esketamine treatment. That’s what I ended up doing in my patient.
Another possible issue is that some patients may feel stimulated for several hours after the ketamine infusions. In such cases, we may need to avoid giving the stimulant even later in the day or to give a lower dose than what the patient was used to.
Lastly, a patient who is receiving a course of ketamine may feel stimulated even on days when ketamine is not given. This is what happened with my patient.
in patients who are receiving treatment with ketamine/ esketamine and were on treatment with a stimulant, we should:
A. Monitor the patient for overstimulation
B. Hold the stimulant on the morning of the treatment with ketamine/ esketamine
C. Consider changing to a short-acting preparation of the stimulant
D. Using a lower dose of the stimulant than the patient was previously on.
Esketamine nasal spray (brand name Spravato): Efficacy for so-called “treatment-resistant” depression
Grunebaum MF, Ellis SP, Keilp JG, Moitra VK, Cooper TB, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. Bipolar Disord. 2017 May;19(3):176-183. doi: 10.1111/bdi.12487. Epub 2017 Apr 28. PubMed PMID: 28452409.
Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. 2018 Apr 1;175(4):327-335. doi: 10.1176/appi.ajp.2017.17060647. Epub 2017 Dec 5. PubMed PMID: 29202655; PubMed Central PMCID: PMC5880701.
Ionescu DF, Bentley KH, Eikermann M, Taylor N, Akeju O, Swee MB, Pavone KJ, Petrie SR, Dording C, Mischoulon D, Alpert JE, Brown EN, Baer L, Nock MK, Fava M, Cusin C. Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial. J Affect Disord. 2019 Jan 15;243:516-524. doi: 10.1016/j.jad.2018.09.037. Epub 2018 Sep 17. PubMed PMID: 30286416.
Copyright 2019, Rajnish Mago, MD. All rights reserved. May not be reproduced in any form without express written permission.
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