Ketamine, a substance traditionally used as an anesthetic, has been found to be beneficial for treating mental health issues including depression and anxiety.
A new study published in the Journal of Clinical Pyschiatry revealed that people who received intravenous ketamine treatments showed clear improvement in their anxiety, depression, and suicidal ideation symptoms.
While the new research leaves some unanswered gaps, it joins a growing body of studies that indicate ketamine treatment could become more widely accessible in the coming years for those looking for effective mental health treatments. It’s a development that is especially relevant during an era when a burgeoning national—and global—mental health crisis means experts are looking for new ways to reach people who need support.
Here’s a closer look at the latest study and the growing body of research supporting ketamine treatments for mental health.
The new study used data collected from 424 people who were being examined for treatment-resistant depression. The individuals studied were seeking treatment in Virginia from November 2017 through May 2021 at three ketamine infusions clinics that all focus on treating those who have anxiety, suicidal ideation, or depression.
Each individual received six infusions within 21 days and “maintenance infusions” were offered based on clinical response, according to the study.
Within the six-week time frame of initial treatment, 50% responded to the treatment and 20% showed remission of their depressive symptoms. There was also a 50% reduction in self-harm and suicidal ideation symptoms within this period. After six infusions, half of those with suicidal ideation symptoms “at baseline, no longer had it,” the study said.
Following a total of 10 infusions, there was a 72% response rate among participants and remission of depressive symptoms increased to 38%. Additionally, researchers found a 30% reduction in anxiety symptoms during the treatment period.
Most striking to the research team was that they saw “up to 85% resolution of suicidal ideations,” lead study author Patrick Oliver, MD, medical director of MindPeace Clinics, told Health.
Questions Surround Ketamine
While ketamine has been used since the 1960s as an anesthetic for short-term sedation to induce sleep before and during surgery, it also has a less than savory reputation for its misuse. Ketamine has a history of being used as a “club drug” called Special K that can be dangerous, producing intense dissociative effects for the user.
Aside from its club reputation, there has also been some criticism around the new study including that it had no control group. A control group is a group of people participating in a study who are not administered the drug or experimental treatment that is being tested and thus can be used as a benchmark to measure the study results.
The study also relied upon self-reported surveys of participants following their treatments and the researchers didn’t look at any negative outcomes or side effects from the ketamine infusions. These study limitations may raise questions over ketamine’s safety.
When asked whether the new research paints a full picture of the ramifications of ketamine usage for mental health, Dr. Oliver said that while it is “a fair criticism” that they didn’t include an assessment of side effects the next study will.
“Most were mild, such as nausea, rarely vomiting, and anxiety during the infusion. These were treated with anti-nausea and anti-anxiety medications. Our next study, which will likely be published next year will have more than 1,000 patients included, and include data on side effects,” Dr. Oliver explained. “That being said, the real point of this study was, ‘Did ketamine work to treat these mood disorders and suicidal ideations?’ The simple answer is that it worked very well, better than virtually anything.”
Controlling for ketamine is very difficult to do, Dr. Oliver added.
“Additionally, given that we know that this works to resolve suicidal ideations, and the ultimate result of that for nearly 50,000 US patients annually is death, is using a control group ethical? To use an analogy, we don’t have a large randomly controlled trial of parachutes,” Dr. Oliver said.
Gerard Sanacora, PhD,MD, the George D. and Esther S. Gross Professor of Psychiatry, Director of the Yale Depression Research Program and Co-Director of the Yale New Haven Hospital Interventional Psychiatry Service, is an expert in this field. He’s treated people with ketamine in his lab since 2004.
Dr. Sanacora told Health that the “lack of adverse event data” in this study is a major limitation, but added it’s a limitation that exists in “the field in general.”
What’s more, the new study joins a growing body of research focused on the mental health benefits associated with ketamine.
A study in the journal Translational Psychology examined the effectiveness of frequent ketamine infusions compared against a placebo. The results showed great “antidepressant efficacy” when put against the control, but as with the new study, the authors write that more needs to be known about not just how ketamine works but the effective dosing amounts that would be needed to treat depression.
Separately, a 2019 study in the Indian Journal of Psychiatry found ketamine infusions to be effective at treating depression and anxiety, among other conditions, with the authors writing “ketamine has a robust and rapid effect on depression, which was seen immediately after the administration of ketamine and sustained at the end of 1 month.”
When asked to put his own work in context, Dr. Oliver said his study provides a larger sample of people than others like it and pointed to the relatively high remission rates of depressive symptoms.
He said this data — along with past research conducted by others — gives a picture of the fact that “this is a repeatable and validated treatment.”
“Additionally, it shows up to 30% remission of ‘Generalized Anxiety Symptoms,’ which is a huge amount, and a fix, not just like benzodiazepines, which cover up the symptoms,” Dr. Oliver added.
Is Ketamine Right for Me?
Most ketamine research has been conducted on people who have unipolar major depressive disorder, which “has proven difficult to treat with more standard treatment approaches,” Dr. Sanacora said.
“Our best evidence is for patients with unipolar major depressive disorder who have not responded to adequate doses and courses of standard antidepressant treatments in the past,” he explained. “Although there is some promising data suggesting efficacy in PTSD, bipolar depression and possibly OCD and even the mood aspects of Parkinson’s disease, the further you get away from the diagnosis of major depressive disorder with the characteristics noted above, the weaker the evidence becomes.”
When asked who might not be appropriate for ketamine infusions, Dr. Sanacora pointed to the U.S. Food and Drug Administration’s guidance on its 2019 approval for Spravato—a nasal spray that contains esketamine—derived from ketamine—to treat depression. The usage warnings for Spravato may serve as something of a guidepost moving forward with ketamine, said Dr. Sanacora.
That spray includes a warning for people with “aneurysmal vascular disease, including thoracic and abdominal aorta, intracranial and peripheral arterial vessels, or arteriovenous malformation.” Additionally, “people with a history of intracerebral hemorrhage as well as hypersensitivity to esketamine or ketamine, or any of the excipients,” Dr. Sanacora added.
Dr. Sanacora said he “sees no reason to think it would be different for IV ketamine.”
There are additional warnings for esketamine that could potentially apply to IV-delivered ketamine. They include potential harm to patients at risk of potential misuse or history of substance abuse disorder, and patients at risk of cardiovascular events due to the increased blood pressure and heart rate that is seen with ketamine, Dr. Sanacora said.
“Additionally, there is concern for patients that may have difficulty tolerating the acute effects on perception and cognition. This may include patients with psychosis,” he added
Right now, the Spravato nasal spray has been approved by the FDA for indications of treatment-resistant depression and major depressive disorder with suicidal ideation. Dr. Sanacora noted that many insurers do cover this version of the treatment.
IV-administered infusions are not yet widely available for mental health therapy. To begin with, infusions of ketamine aren’t approved to treat depression and are considered “off label” usage when being provided. In addition, insurance doesn’t cover usage of IV ketamine for depression even if it is recommended by your physician.
Dr. Oliver believes that “in five years,” these infusions will be applied “as a first-line treatment for major depression.” He also said it will most likely be an “early option” for moderate depression, as well as being used for anxiety, and first-line therapy for suicidal ideations.
“It’s a generic medication, so no big pharma money is pushing it,” he said.
However, the FDA’s approval of the nasal spray could indicate that there may be similar approval for infusions in the future. In the case of esketamine, there was a thorough collection of “adverse event data” in its trial phase before the FDA approval, Dr. Oliver said.
Still, much more work needs to be done, especially when you consider that providers in this field are using largely varying doses of ketamine. Sanacora would like to see more standards applied across the board as ketamine therapy grows in adoption as a regular mental health treatment.
“I, and several of my colleagues have been calling for a central registry surrounding the use of ketamine for these purposes to allow us to collect meaningful high quality data on the drug’s safety and efficacy,” Dr. Sanacora said.
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