Danielle Cosgrove rested in a hospital bed with an IV slowly pumping the meds into her veins. She knew the drugs were working when the walls started to melt.
"It was very, very scary," the petite 27-year-old said of her first experience with ketamine-infusion therapy, an increasingly popular but largely unregulated treatment for ailments ranging from intractable depression to untreatable pain, for which she is an outspoken advocate. "I thought the walls were made of icing and they were melting down on top of me trying to suffocate me."
For Danielle, the only thing worse than the hallucinations is her constant, excruciating pain, the hallmark of Complex Regional Pain Syndrome, a rare neurological disorder she developed after a devastating ATV accident in Qatar in 2010. She experimented with a series of invasive treatments and even strong opiates like Oxycontin, with no end to the pain. As a last resort, she turned to ketamine-infusion therapy in 2011.
"Imagine it as having the volume of your pain system cranked up to a ten—everything that hurts after you develop the disease will hurt more, and everything that hurt beforehand will also hurt more," explained Dr. Enrique Aradillas Lopez, a protégé of ketamine-infusion therapy's American godfather, Dr. Robert Schwartzman, and a high ranking physician in Drexel University's neurology department.
"The neurons that have changed are disinhibited and in a constant state of excitation," like a club kid lost in a K-hole, Dr. Aradillas Lopez explained. "Ketamine blocks the NMDA receptors and gives a chance for the neuron to go back to the way it was before. In a way, it's rebooting your pain system."
It was desperation that pushed Danielle to the street drug—Special K—she had avoided as a student in London. Since starting treatment, she's shuttled between her home in Texas and hospitals first in Chicago and then Philadelphia, subjecting herself to dozens of intravenous ketamine infusions and consecutive days of terrifying drug trips. She carries ketamine pills and a ketamine nasal spray in her purse. For her and untold others, the horse tranquilizer turned trippy club drug is the only medicine that works.
"It's a profoundly valuable drug as [a painkiller]," said Colonel Chester 'Trip' Buckenmaier III, a military physician who championed ketamine as a frontline pain drug for American soldiers wounded in combat. "Ketamine became something that we were falling back on when everything else was maxed-out and failing."
Ketamine infusion therapy started in 1999, and the last decade has seen the rise of more and more unorthodox uses for the operating-room anesthetic, and in the past two years alone, the number of US clinics offering ketamine infusions to treat everything from fibromyalgia, a syndrome that causes long-term, body-wide pain, to eating disorders and OCD has ballooned.
Dr. Aradillas Lopez cited more than a dozen new clinics giving outpatient infusions. Colonel Buckenmaier wouldn't estimate how many military hospitals have adopted ketamine-infusion therapy, but said he's asked for his protocols roughly once a week. Dr. Philip Getson, another Drexel University–affiliated physician, who practices in New Jersey, put the number of clinics closer to 60.
"It's probably the antidepressant drug with the least significant side effects of any other antidepressant agent now in use," said Dr. Glen Brooks, an anesthesiologist who opened the New York Ketamine Infusions center in downtown Manhattan to treat patients with drug-resistant depression two years ago. "Most of my patients are suicidal. Most have failed electroconvulsive therapy and transcranial magnetic stimulation, and in spite of that I'll still see a significant number of patients that have a dramatic response to ketamine."
Researchers believe the drug works similarly to other antidepressants, by regulating the activity of specific electrochemicals in the brain. The difference, Dr. Brooks explained, is that while other antidepressants act on monoamines like serotonin, norepinephrine, or dopamine, which together account for just 15 percent of the brain's neurotransmitters, ketamine targets glutamate, an amino acid that accounts for 50 percent of nervous tissue in the body. SSRIs must be taken every day, but a single shot of Special K can keep a patient smiling for months.
"The only real side effect of ketamine is during the infusion itself: There is a sort of out-of-body experience," Brooks said. "Most patients actually enjoy it. Young patients listening to their own music can really get into this out-of-body thing."
Some patients described feeling goofy and happy for about a day afterward, while Danielle described more of a drained and edgy feeling that made her antisocial for a few days.
Ketamine is FDA-approved strictly as an induction agent—or what knocks you out on the operating table. But off-label prescriptions are a common practice in the medical field, like the seizure medication Neurontin prescribed for anxiety or the narcolepsy drug Provigil given to patients with ADD.
Ketamine is different in part because it's most effective as an IV drug, one that must be administered in a hospital or clinic, often in combination with other strong drugs like Versed, to counteract its hallucinogenic effects. Infusions can last for hours and are sometimes spread over days. Experts have yet to agree on how much and how many doses of ketamine make a safe and therapeutic treatment.
"I do ketamine regularly: It can be up to every two weeks or every two months," Danielle said. "It is a heavy drug to be putting into your body constantly. You want to be able to say, I'm doing this until this point."
The lack of large-scale clinical trials and funding makes that point difficult to identify. Depending on the patient and the condition, Brooks administers the infusion in one- or two-hour doses while patients sit in a chair, similar to chemo or dialysis. Aradillas Lopez orders a ten-day stay with slow, continuous infusions at intensive care units.
"This drug will never be approved by the FDA [for therapy]," Dr. Brooks said, noting that without the administration's bureaucratic gold star, most insurance companies won't foot the bill, either. "There aren't that many of us out here doing this, so there's no standard of care."
According Buckenmaier, who's spent his career treating injuries that would have been universally fatal even a decade earlier, the medical establishment is losing out on one of the best pain drugs there is.
"In my 26-year career in the military, the deaths that I've seen from pain management have been from opioids," the Colonel said. "I often say, if only the drug in that machine had been ketamine, those people would be alive today."
But for now, ketamine-infusion therapy is likely to languish without set standards or FDA approval, confined to a handful of military hospitals and a smattering of research institutions, with offshoot clinics like Brooks's few and far between.
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