Ketamine is going mainstream. Jacqueline Froehlich

Mark Holaway abruptly ended his 20-year career as a paramedic and firefighter after suffering a breakdown and being diagnosed with complex post-traumatic stress disorder. 

Decades of responding to horrific fires, destroyed lives and property, mixed up with unresolved personal trauma, had buried him into what felt like inextricable depression. “It feels like you’re trapped in a nightmare,” he said. 

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He sought cognitive therapy, which helped him to learn a new way of thinking. But it didn’t help resolve his chronic despair. That’s when his therapist asked him to consider ketamine therapy.

Years back while working as a paramedic, Holaway had injected ketamine — a widely used inexpensive surgical anesthetic — into critically injured people. “I would administer it for extreme pain to safely help accident victims disassociate from their physical injuries — putting them in a far better place,” Holaway said.

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But he’d never heard of ketamine being used to treat depression. 

After an especially bad episode, Holaway decided to give it a shot. His therapist referred him to Dr. Kathleen Wong, a psychiatrist who operates an outpatient ketamine therapy clinic in Fayetteville, part of a group mental health practice called Bridges to Wellbeing.

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Holaway said the treatment lifted him out of profound suffering. “I hadn’t been in that safe of a space since I was a young child,” he said. 

Mark Holaway spends time in the garden with Coco the cat.

A neurology fellow of the American Psychiatric Association and an American Board of Psychiatry and Neurology Diplomate, Wong is among the first physicians in Arkansas to pioneer the use of ketamine therapy to improve mental health. She started offering the treatment more than five years ago. “I base my ketamine infusion protocol on those developed by the National Institute of Mental Health,” she said. “I offer ketamine infusions for refractory, or treatment-resistant, depression, as well as anxiety disorders.”

Ketamine hydrochloride was approved by the U.S. Food and Drug Administration in 1970 for use as an anesthetic agent. But more physicians are administering it off-label to treat psychiatric disorders.  

After assessing needs and determining proper dosage based on weight, Wong settles patients into one of several private infusion suites. “My nurse starts an IV while the patient sits quietly in a recliner with an ambient spa playlist on headphones, wearing a sleep mask,” she explained. Treatments last around 40 minutes. Patients never lose consciousness. Some may experience unusual thoughts, euphoria or out-of-body experiences. They may see bright colors or unusual visions. Side effects may include a slight rise in blood pressure and wooziness or nausea, which can be treated with medication, Wong said, and quickly subside. Patients are advised to not drive for 24 hours post treatment. 

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Patients report significant improvement after ketamine infusions.

Wong typically prescribes six low-dose infusions over several weeks. Patients report rapid improvements in mood, sleep, social engagement and appetite. Ketamine infusion may also relieve self-destructive thinking.

“What has been exciting and promising is research out of Europe [showing ketamine] to be very powerful in helping people with alcohol misuse disorders,” Wong said. “And there’s some fascinating research with borderline personality disorder and autism spectrum disorder — although that’s tentative.”

Despite promising research, Wong said it’s unlikely that ketamine will win FDA approval for psychiatric treatment in the United States. That’s because such approval would require expensive and extensive studies subject to publication and peer review. The U.S. patent on ketamine expired in 2002, so costly clinical trials for the compound won’t yield any financial returns on pharmaceutical investment. “The vial of ketamine is generic,” Wong said. “There is not money to be made in researching it.” 

But two years ago, Janssen Pharmaceutical Companies, a subsidiary of Johnson & Johnson, won FDA approval for Spravato, an esketamine nasal spray for treatment-resistant depression. Generic ketamine contains both R-ketamine and S-ketamine enantiomers (or mirror image molecules). Janssen isolated the S-ketamine, or esketamine in order to patent and monetize Spravato, one of the first antidepressant drugs to come on the market in decades. The drug is typically administered in a clinical setting twice a week for the first month, then maintained once a week, or as needed. As an FDA-approved treatment, Spravato may be covered by medical insurance, depending on the provider. Spravato is taken in combination with oral antidepressants, according to the label. 

Dr. Eric Ross, a psychiatry resident at Massachusetts General Hospital and McLean Hospital, said Spravato’s high price is a barrier. The drug costs around $300 per dose, and would need to fall to $140 or less per dose to be cost-effective, he calculated. 

Scant research exists comparing nasal esketamine to its parent IV compound ketamine, due to the latter’s generic status. But according to National Institute of Mental Health research, a six-ketamine IV infusion series has been shown to have more than a 70% success rate in the treatment of major depression. 

A single IV infusion of ketamine typically will cost between $400 and $800, depending on the clinic, administered on average six times over a span of weeks. Unlike with Spravato, insurance providers do not reimburse for ketamine infusion therapy because it’s deemed experimental and off-label.

So how does it work? Chronic mental illness, life stress, chemical or substance dependence can impair brain function. Ketamine has been shown to promote both neurogenesis — the formation of new brain neurons — and synaptogenesis, the formation of new connections between neurons. “These effects can be seen within the brain within 110 minutes of the first infusion,” Wong said, “and a series of six can set that person in a whole new place from a structural standpoint.”

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A report published two years ago in Yale Medicine magazine referred to ketamine as an “anti-medication” medication. Conventional antidepressant drugs slowly release chemicals such as serotonin, norepinephrine and dopamine providing relief over time. Because ketamine has been shown to prompt formation of new neural connections, it may offer a more permanent solution. Ketamine may make the brain more adaptable and able to create new pathways, giving patients the opportunity to develop more positive thoughts and behaviors. 

Jacqueline Froehlich
Dr. Kathleen Wong is a pioneer in using ketamine to treat severe depression in Arkansas.

More than a half-dozen clinics in Arkansas offer off-label ketamine infusion therapy for depression, anxiety, obsessive compulsive disorder, postpartum depression, bipolar disorder and pain. The University of Arkansas for Medical Sciences in Little Rock started offering ketamine treatment at its Psychiatric Research Institute eight years ago. Dr. Jeffrey Clothier, institute director, described ketamine as “a remarkable addition to our armamentarium.”

Still, the drug has its detractors. Ketamine has a decades-long history as an underground club drug. Nicknamed “Special K,” users either snort the white powdery compound or inject it. According to the National Institute on Drug Abuse, ketamine acts on brain receptors to cause dissociative states, hallucinations and delirium. Illegal use of ketamine in high doses can impair motor function, trigger high blood pressure and may cause respiratory failure. Increasing availability of illegal opioid drugs in the 2000s led to a decline in recreational ketamine use, just as its clinical psychiatric benefits were beginning to be seriously studied.

Those benefits were a life changer for Sarah James, a 50-year-old writer in Northwest Arkansas who opted to not use her real name here to protect her identity. She is diagnosed with bipolar disorder. “It’s like extreme waves of depression, darkness and suicidal ideations, combined, for me, with agitation, extreme anxious feelings, like I have to do something,” she said.

James tried various psychiatric meds, which didn’t help. “I was in a dangerous place,” she said. “I had made plans to burn all my possessions, ramping up to attempting suicide again.”

That was until James’ psychotherapist referred her to Dr. Wong. “It’s an amazing experience,” she said about her first ketamine infusion. “It’s sort of like a hallucinogenic high, and it has the quality of a sweeping uplift. Right from the start.”

After her first treatment she returned home to her family, who were hosting out-of-town guests. “Normally I would seclude myself in my room,” she said. “It would have been too much stimulation, thrown me into a bad spinout.” This time, though, James said she spent the evening cross-legged on the living room floor, chatting with everyone. “I wasn’t jubilant, but I was happy and engaged,” she said. 

That was in late 2017. James continues with occasional booster infusions and recommends ketamine therapy to anyone who is dangerously depressed. “I honestly don’t think I would be walking around on the planet Earth if not for ketamine,” James said. “I tried meds for 15 years, like many bipolar people. The despair starts to emerge when you try yet another thing that doesn’t work. It’s cumulative. It’s horrible. I wasn’t functioning.”

Retired firefighter Mark Holaway said ketamine saved his life as well. His mind started working again once he started treatments, which was a challenge in itself, he said. “After suffering with PTSD for so long, it was disorienting, unfamiliar.” Processing treatment outcomes with his ketamine-informed psychotherapist helped him sort out the experience. Looking back now, Holaway said, he’s surprised by how far he’s come. “I didn’t understand the depth of where I was until I was out of that hole.”

Compounding pharmacies are increasingly offering prescription generic ketamine in troches (fast-dissolving lozenges), tablets and intranasal sprays to treat depression and pain. 

To help save IV infusion treatment costs, Holaway said his primary care physician suggested he try a compounded ketamine nasal spray dispensed by Westside Health Mart Pharmacy in Springdale. “A month’s supply, which provides up to five sprays per day, costs around $45,” pharmacist and owner John Ragan said. At first Holaway used the spray once a day. “I was doing that for a while,” he said, “but with time I was needing less and less, and less and less.”

Since his medical retirement from firefighting, Holaway operates an independent remodeling and building company. He practices yoga, meditation and breathwork to alleviate stray PTSD symptoms. 

“But if I have a stressful day, or stress insult, and my nervous system doesn’t feel balanced, I will take a small dose of ketamine before bed and will wake up in the morning, reset.”

Holaway said insurance providers for first responders in Arkansas need to be convinced about the benefits of psychiatric ketamine treatment. “The rigors of my job almost cost me my life,” he said. “I am convinced that ketamine is one of the cheapest options for treating PTSD. The money I invested was the best money I ever spent. It increased my productivity, my interactions with my family and community, tremendously.”  

Jacqueline Froelich is an investigative journalist and has been a news producer for KUAF National Public Radio since 1998.