Monitoring Patients on Esketamine Therapy for Treatment-Resistant Depression

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Strategies that can be used to monitor patients on intranasal esketamine therapy for treatment-resistant depression, with special considerations surrounding blood pressure management.


Steven Levine, MD: You mentioned an important contraindication, which is bipolar disorder. Are there other contraindications to intranasal esketamine?

Patricia Ares-Romero, MD, FASAM: Yes. We need to look at patients with a history of substance abuse. It’s not a contraindication, but it’s something to always keep in the back of your mind. Aneurysms are a contraindication for our patients. Increased intracranial pressure is something we also need to ask about. When you have a good clinical history of your patient, you’ll be able to take a deep dive and look at these things.

Lisa Harding, MD: Yes. If I can comment on that: Ketamine is a dissociative anesthetic. As Patricia mentioned, it’s not 0 risk with patients with substance abuse. But this is tailored medicine. That is what we all try to practice now. If I have a patient who’s actively engaged in substance-use treatment, who has a therapist, whose family and family care doctor are involved, and we all come to a consensus that this treatment is worth exploring with someone who’s having suicidal thoughts and very hard-to-treat depression, I would absolutely try it. We don’t give these treatments in a vacuum. There’s close follow-up, checking in with the patient afterward, and weekly follow-up with my patients with both IV [intravenous] and esketamine. It’s the movement that we’re working toward right now with integrative medicine. We all have a multidisciplinary approach to our patients, and they are at the center.

Steven Levine, MD: Absolutely.

Angelos Halaris, MD, PhD, APA, ACNP, CINP: May I pitch in very quickly? I couldn’t agree more with what Lisa said. It’s not a contraindication per se, but I’d like to be on record with a note of caution with hypertension.

Patricia Ares-Romero, MD, FASAM: Yes.

Angelos Halaris, MD, PhD, APA, ACNP, CINP: Hypertension is a major issue because it could potentially increase significantly following administration. It might not increase down the road, but it could initially. Having absolute control of high blood pressure is of the utmost importance.

Steven Levine, MD: What types of blood pressure changes do you typically see when treating a patient?

Angelos Halaris, MD, PhD, APA, ACNP, CINP: We usually see a big increase within the first 90 minutes or less, or 30 to 45 minutes. I haven’t seen it personally, except for 1 patient who came in referred by a PCP [primary care physician] or an internist. By history, he was well controlled on the following blood pressure medications. He was on 2 antihypertensives, and I thought this was OK. But following the first or second administration, his systolic blood pressure went up to 200 mm Hg. That’s worrisome. It took awhile longer for us to bring it down. We didn’t have to send him to the emergency department or do anything. We made sure he rested comfortably, we dimmed the lights, we didn’t have any conversations, and we hydrated. After the end of 2½ hours of observation, he was safe to be discharged to the custody of somebody, who would usually be a spouse.

After that, I suspended further treatments until the hypertension was brought at a control with the addition of a third antihypertensive, namely hydralazine. That made all the difference in the world. I waited another 2 to 3 weeks to make sure his blood pressure had stabilized following the adjustment of blood pressure medications.

Lisa Harding, MD: Definitely. Following up on that excellent point, the first consensus paper was written when IV ketamine was expanding its implementation here. For example, in the clinic, we don’t start treatment in a patient who is 140/90 mm Hg. It’s a hard stop. I can exert a little more control in an IV setting when those pressures start to go high. For me, that’s usually 160 mm Hg with a diastolic of 100 mm Hg, and I can hit pause on that IV and then we administer medications to bring it down. As you were pointing out, esketamine is a little more tricky because once it’s in, it’s in. It’s about monitoring the patient. Those are fantastic points, so thanks for raising them.

Transcript Edited for Clarity


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