Conference Coverage

Questions surround ‘exciting’ intranasal esketamine



– While an “exciting” ketamine-based product is finally available and approved to treat treatment-resistant depression (TRD), there are still plenty of questions about the use of intranasal esketamine, a psychiatrist told colleagues.

Dr. Sanjay Mathew

Dr. Sanjay J. Mathew

“We have a lot of unmet needs in terms of research,” said Sanjay J. Mathew, MD, of Baylor College of Medicine and Michael E. Debakey Veterans Affairs Medical Center, both in Houston, at the annual Psych Congress. “What do we do in the long term? What are the dosing strategies and response predictors? What about elderly patients?”

The Food and Drug Administration approved esketamine nasal spray (Spravato) for TRD in March 2019. Patients with TRD are defined as those with major depressive disorder who have failed at least two different antidepressants.

Dr. Mathew highlighted a 2019 randomized, double-blind, controlled study of patients who reached stable remission after 16 weeks on esketamine. It revealed there’s “a significant enhancement of the time to relapse for patients who remained on ketamine [compared with placebo] – a 51% risk reduction in the median number of days to relapse” (JAMA Psychiatry. 2019;76[9]:893-903).

However, about a quarter of patients still relapsed over the time of the study, Dr. Mathew said. “While this is certainly exciting, we need to talk to our patients about this and set expectations. And we need to emphasize close vigilance, follow-up, and psychotherapy.”

Patients should understand that, if patients are doing remarkably well at 16 weeks, “you’re not out of the woods. You really need to take it long term,” he said.

Dr. Mathew emphasized that patients must take the drug under supervision in a certified facility. “It’s a quick and simple process to do it [get certified] and get registered,” he said. Patients must be monitored over 2 hours and not drive for the rest of the day.

“You need space for some privacy, so a busy [postanesthesia care unit] or ER setting may not be optimal,” he said, adding that, “if you only have one office, it’s hard to pull this off for a number of logistical reasons.”

Dr. Mathew recommended lowering the level of stimulation in the room where the drug is administered. “We have a VA setting that can be loud with code greens blasting over the speaker,” he said. “That is not optimal, but at least we have a private room for our IV infusions. Keep the lights muted, let the patient listen to peaceful music that they enjoy. Having a family member close by can be helpful and comforting to them.”

He added that “you do need a way to recline the head. Having a barber-type chair would be necessary.”

Side effects are common, he said. Sedation is a major risk (49%-61%), as is dissociation (61%-75%). “It’s primarily a sense of alteration – perceptual alterations, altered sense of time, unreality, being disconnected from body, feeling unusually big in fingers or hands, or feeling like you’re unusually tall or skinny.”

Moving forward, more data about long-term effects and ideal doses are needed. “There are many clinics that go above 0.5 milligrams per kg, and some even go to 2. We have no good data,” he said.

People aged over 65 years have lower response rates, and men seem to respond less than women. Dr. Mathew also noted that the studies into the drug generally limited the number of antidepressant failures in patients: “Are there patients too refractory to be considered for this? How refractory is too refractory?”

Dr. Mathew reported various disclosures including a relationship with Janssen, manufacturer of intranasal esketamine.

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