Ketamine, a drug long used as an anesthetic and illicitly for recreation, has come into increasing usage locally and across the country as a medication against treatment-oriented depression.
Providers say it is a breakthrough for many severely suffering patients and that its therapeutic use may increase in the years ahead, though roadblocks around getting insurance to cover it make it difficult for patients to access.
Ketamine, first synthesized in 1962, is a Schedule III drug under federal law, found to have a lower potential for abuse and an accepted medical use. Researchers found use in it as an anesthetic, and the Food and Drug Administration first approved its medical use for this purpose in 1970. It was commonly used in the Vietnam War, because it doesn't suppress breathing and blood pressure like other anesthetics. The World Health Organization lists it as an essential medicine.
While recreational ketamine is usually taken nasally as a powder, its clinical administration is intravenously or as a prescription nasal spray. The University of Arkansas for Medical Sciences first began intravenous doses for psychiatric patients in 1999; standalone psychiatric clinics were administering it statewide by the late 2010s.
"With medications like this that have very long histories of FDA approval, what you end up seeing is that they typically have clinical efficacy for things that you wouldn't know they would have," said Brian Mears, founder and president of Alleviant Integrated Mental Health, which has six clinics across Arkansas. "People who were undergoing anesthetics would wake up and over the next weeks of months have less depression. That started research in the early '90s."
However, insurers do not cover intravenous ketamine treatment because of its off-label use: ketamine itself has never been approved for psychiatric uses. Insurance companies may, however, cover the nasal spray Spravato, an FDA-approved molecular mirror of ketamine used to treat depression. Alleviant's breakdown of ketamine care is half-and-half Spravato and IV. Both have to be given in a clinical setting in appointments that last several hours.
Mears said ketamine therapy represents 0.6% of the work his six statewide clinics do, or around 420 patients with treatment-resistant depression, PTSD, obsessive-compulsive disorder, postpartum depression, anxiety or suicidal ideation or intent across all its clinics.
He prefers intravenous treatment because it acts more quickly than Spravato on patients, saying, "Anything we get through the nose can't be as fast as IV." The rapid onset can sometimes provide significant relief after a first session. That can be particularly beneficial for patients on the precipice of the most-severe outcomes because of treatment-resistant depression
"If you're acutely suicidal and you need something to pull that back for safety reasons, or if you're so depressed and so overwhelmed and you're trying to switch meds or increase medications, then it kind of bridges you a gap," said Dr. Lou Ann Eads, a psychiatrist at the University of Arkansas for Medical Sciences who administers ketamine therapy.
Even if depression does not end with the treatment, if it causes the severity of patients' symptoms to decrease, issues like acute suicidal ideation can retreat.
Because insurance companies do not cover intravenous ketamine therapy, patients face high out-of-pocket costs -- $525 for each treatment at UAMS with multiple sessions necessary. Eads said that she could not say if intravenous treatment is profitable for all clinics but that it is not for UAMS.
For Spravato, providers have to demonstrate to insurance companies that their patients have treatment-resistant depression based on the number of other therapies they take that fail. Insurers may require patients to have an unsuccessful outcome with medications of different classes or medication coupled with psychotherapy before prescribing Spravato.
Even with insurance, Eads noted that ketamine is still a very expensive drug. Working with insurance to administer it can also be difficult: She recalled one patient whose insurance insists that UAMS get the Spravato shipped from New York, rather than its own pharmacy, before the clinic administers it to her.
There are also more established therapies that can make a difference with treatment-resistant depression. Transcranial magnetic stimulation (TMS), in which a magnetic field causes an electric current in certain areas of the brain, can help 50% to 60% of people with mild-to-moderate depression, Eads said, adding that it is particularly helpful for patients who have significant side effects from medications.
She called ECT, electroconvulsive therapy, the "gold standard" for treating treatment-depression. "But it will not take the place of medications," Eads said. You may be able to back off of medications, the number or the high dosage, but it's a way to stimulate the brain and target those areas that are not functioning very well with depression over time."
ECT does have side effects, including memory damage.
"I think that we're beginning to see some newer modalities of being able to treat depression in hopefully a little bit better way," Eads said.