From the Journals
APA task force urges caution in off-label use of ketamine for mood disorders
An APA task force looks at the state of the field on the use of ketamine for treating refractory mood disorders.
‘Mystical experiences’
Dr. Markey said a retrospective analysis of about 740 patients at her chain’s clinics showed a response rate of about 75%. Other research has shown similarly high response levels.
“Multiple clinical trials suggest that a single low dose (0.5mg/kg) of IV ketamine results in a 50%-70% response rate in patients with treatment-resistant depression,” reported a 2016 clinical review. “Additional research has shown that depressed patients can experience symptom relief as early as 2 [hours], and lasting up to 2 weeks after a single administration of IV ketamine,” according to the review in Evidence Based Mental Health (2016 May;19[2]:35-8).
Dr. Gregory Simelgor
Adverse effects can include nausea and headache in patients with a history of migraine, he said. Over the long term, ketamine use can lead to incontinence and urinary urgency, he said.
As for ketamine addiction, Dr. Simelgor calls it unlikely at the lower doses that are used. However, he said, “I can’t say 100% that it won’t cause addiction.”
Who benefits? The jury’s still out
Considering its positive effects, why shouldn’t the mental health community embrace ketamine? Because, two prominent researchers say, best practices are still absent in a whole range of areas.
For example, there’s no agreement about who should undergo ketamine treatments beyond patients with treatment-resistant depression, especially those who have failed or cannot undergo electroconvulsive therapy. Ketamine therapy also is being touted by some as a treatment for a long list of other conditions from obsessive-compulsive disorder and anxiety to fibromyalgia and chronic pain disorders.
There are also limited data about dosing, making it “not possible to clarify the relative benefits and risks of doses other than 0.5 mg/kg delivered intravenously over 40 minutes,” cautioned Dr. Sanacora and Samuel T. Wilkinson, MD, also at Yale, in a 2017 commentary in JAMA (2017;318[9]:793-4).
In fact, they write, “Most published data supporting the use of ketamine as a treatment for mood disorders are based on trials that have followed up patients for just 1 week after a single administration of the drug.”
Unchartered waters
There’s also no accepted protocol beyond a typical six treatments over 2 or more weeks. This is relevant because the benefits of a series of treatments often fade away after a few weeks.
“Some patients describe the results lasting indefinitely, while most patients who respond to the treatments get to the point where they are going roughly 4-12 weeks with sustained results,” Dr. Wells said.
“When the effects start to wear off, they don’t crash,” said Dr. Abreu. Instead, he said, symptoms slowly reappear.
It’s typical for patients at Dr. Abreu’s clinic and others to return within a couple of months to go through another round of ketamine treatments. In some cases, “they continue to see us indefinitely to get them back up to where they need to be with a booster type of session,” he said.
Ketamine treatment costs vary widely, and insurers don’t cover this off-label treatment. The clinic operators quoted in this article reported a range of per-infusion costs from $350 (Dr. Markey’s clinic in Denver) to $675 (Dr. Abreu’s clinics in the Northwest).
“We have to have a talk with them: Can you afford this? This is going to take a significant amount of money every month to keep you well,” Dr. Abreu said. On the other hand, he said, the need for other medications goes away, eliminating that cost. (“They’re on [selective serotonin reputake inhibitors] usually,” he said, “but those drugs don’t work.”)
Nonpsychiatrists in forefront
At Dr. Markey’s clinic in Denver, all patients are required to see either her or a psychiatrist colleague. Some other ketamine clinics are run by psychiatrists, but that’s far from common.
Clinics often have no mental health professionals on staff and are run by anesthesiologists or other kinds of physicians.
Some clinic owners, Dr. Wells said, require patients to be under the care of a psychiatrist, neurologist, pain doctor, or other appropriate professional. “I do not intend, nor do I act, to displace psychiatrists, or the relationships our patients have with their psychiatrists, or the care they receive from their psychiatrists,” she said.
In the Northwest, Dr. Abreu said his patients take mood questionnaires, and he’s experimenting with a text-based mood monitoring system. In the Minneapolis area, anesthesiologist Dr. Simelgor is looking for a psychiatrist or psychiatrist partner for his ketamine clinic. “My thinking,” he said, “is that we need to work together.”
Still, there do not appear to be any requirements that ketamine clinic practitioners have connections to mental health professionals. Yet, as Dr. Sanacora put it: “Delivering the drug is the easiest part of the treatment. The hard part is managing the depression.”
Dr. Lieberman, Dr. Wells, Dr. Abreu, Dr. Simelgor, and Dr. Markey reported no relevant disclosures. Dr. Sanacora reported consulting fees and research contracts for multiple drug makers over the past 24 months. He holds shares in Biohaven Pharmaceuticals and is a coinventor on a U.S. patent (No. 8778979) on using glutamate agents to treat mental disorders held by Yale University.