NEW ORLEANS – Ketamine infusions are becoming more and more routine for refractory depression, but the literature is just not clear about the optimal treatment regimen.
Studies have run the gamut from daily, to weekly, to monthly infusions, with scant information on how to predict who will respond and how to maintain response.
Dr. Ranjith Chandrasena
“Almost everybody feels significantly better an hour after the infusion. The question is how long will they continue to feel better, and how to find the ones who will stay well. That’s what we’ve tried to answer here,” said principal investigator and psychiatrist Ranjith Chandrasena, MD, the research center’s scientific director.
Ketamine is dosed at 0.5 mg/kg IV over 45 minutes, delivered in an ambulatory care center under the supervision of a respiratory therapist and a physician assistant, with vital signs monitored every 10 minutes. Patients are cleared ahead of time for anesthesia, since ketamine at higher doses is an anesthetic.
In the induction phase, patients are offered up to three ketamine infusions weekly; if MADRS scores don’t remain below 16 points a month after the last induction dose, ketamine is judged to be ineffective, and the patient is taken off the protocol. A score below 16 “pretty much translates to normal functioning,” Dr. Chandrasena said.
Patients who remain below 16 points a month after their last induction dose are moved onto maintenance and qualify for repeat infusions when their MADRS creeps above 16 points, so long as it’s stayed below 16 for a month or more in the interim. The majority of patients on maintenance go 6 or more weeks between infusions. MADRS scores are assessed weekly over the phone.
For patients on maintenance, scores have dropped from a mean of 28.72 points at baseline to 10.73 points, an impressive improvement in patients with long-standing depression who have failed multiple treatments.
Global Assessment of Functioning scores have improved as well, from a baseline of under 40 points to over 60 points, with improvements in social functioning and the ability to work. A few patients had made serious suicide attempts before starting ketamine; with treatment, “there has been success in keeping patients out of the hospital, with no suicide attempts reported,” Dr. Chandrasena said.
Ketamine’s been well tolerated at the center; no one has been discontinued because of side effects, and only one person has had noticeable hallucinations. “People are telling us that it’s a very pleasant experience,” he said.
But to cut costs and reduce the addiction risk, the investigators are considering nasal esketamine instead of IV ketamine, and rapastinel, an N-methyl-d-aspartate receptor antagonist that doesn’t have the dissociative effects of ketamine. Patients also are being taught how to recognize the signs of relapse, to see whether the medication reduces the need for weekly phone assessments.
“We would like someone to replicate our study. If the results are promising, that would be the time to do a double-blind placebo-controlled trial using this” protocol, Dr. Chandrasena said.
Almost two-thirds of the subjects were women, about a third were men, and a few were transgendered. Ages ranged from 19 to above 70 years, with most patients 30-70 years old.
There was no industry funding for the work, and the investigators had no disclosures.