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Nicole Safran was angry. After several years of different migraine treatments, one of her pain doctors suggested that it might be time to try a drug called ketamine. “Absolutely not,” she told her doctor. She knew about the drug’s shady past as a party drug known as “special K” and she didn’t want to be linked to it in any way.
But Safran was getting desperate. She had developed chronic migraine after a train accident in 2016 when she was 25. Years later, she was still trying to regain control of her life.
In retrospect, says Safran, she likely had undiagnosed symptoms of migraine from childhood, most obviously abdominal pain and nausea. But after the accident, which caused a serious concussion, her symptoms increased exponentially.
She had throbbing pain in her head, jaw, neck, and sinus area, tingling in the back of her head, light sensitivity, tinnitus, and phantom smells and visual effects (auras), among other symptoms. Doctors diagnosed chronic intractable migraine. “I basically had some level of head pain and migraine symptoms every day,” Safran says. And on many of those days, her symptoms were debilitating.
The effects on her work life were immediate. Her managers were confused. She simply wasn’t able to do what she could do before the accident.
“I was very close to losing my job.”
Her social life took a hit as well. “I’ve lost many friends throughout the process, even though I learned they probably really weren’t friends to begin with. But that’s really challenging when you’re in your mid-20s, living in New York City and your whole world comes crashing down around you and you don’t really know what the future holds.”
“People just constantly dismiss you and think, ‘Oh, it’s just a headache,’” Safran says. “No! It’s so much more than that. It is a full-body disease. It impacts every aspect of my life.”
To make things worse, her response to a laundry list of standard medications and therapies had been patchy at best. She could get some moderate relief some of the time, but nothing seemed to really cut through the constant barrage of migraine symptoms for any length of time.
And so in June 2021, after a long discussion with her doctor and some reading about the therapeutic uses of ketamine, she decided to give it a try.
A ‘Game Changer’
For Safran, it turned out to be a game-changer. A 5-day infusion of ketamine in a hospital setting managed to control her most significant migraine symptoms for 3 to 4 months. But it’s not just that it knocked out so many of her migraine symptoms and slowed the relentless onslaught of treatment-resistant symptoms – it also became much easier to control the symptoms that she did have.
“That’s not unusual,” says Stephanie J. Nahas, MD, associate professor of neurology and assistant director of the Headache Medicine Fellowship Program at Thomas Jefferson University in Philadelphia, PA, where they have been treating migraines with ketamine since 2006.
“We have several patients who report this degree of efficacy or even better. I have one patient who gets up to 9 months of excellent control after the 5-day infusion. We have a number of patients who come in every 3-4 months … since it works so well for them,” says Nahas. And it’s particularly in Safran’s type of migraine – intractable, treatment-resistant, chronic migraine – that ketamine infusions can be so effective.
Still, Nahas is cautious about touting ketamine for all migraine patients. “It’s not a treatment to be entered into lightly. In fact, we have all our patients read and sign a lengthy treatment consent before we will prescribe them ketamine.”
More specifically, patients with liver disease, a history of significant substance abuse, and certain psychiatric diagnoses are not good candidates for the drug, she says.
At Jefferson, says Nahas, “Ketamine is something we usually reserve for patients with very high disease burden and multiple prior treatment failures.”
And Nahas is less enthusiastic about other protocols for the delivery like intranasal and oral, which deliver much lower doses of ketamine safer for home use.
“We have not found that daily oral or intranasal treatment is very helpful, and it carries a lot of risks,” says Nahas.
Safran’s experience aligns with this. There is an outpatient form of ketamine given through an IV that requires at least 45 minutes of in-office time that can help break through a single bad migraine, but it’s the 5-day infusion that makes the biggest difference, she says.
“Nothing else puts my symptoms on the back burner for so long.”
Not Without Risks
Ketamine is not a simple medication. To start with, it’s a controlled substance with high abuse potential. This is particularly an issue for Safran, who wants to work in health care and cannot use the substance within 24 hours of being in a clinical setting.
And it can be tricky to use, says Steven P. Cohen, MD, professor of anesthesiology and critical care medicine and director of the Blaustein Pain Treatment Center at the Johns Hopkins School of Medicine.
An overly high dose could cause loss of consciousness. It also can cause serious liver and spinal cord damage and theoretically even brain damage, Cohen says.
Even with correct use, it can have serious side effects like intoxication (the most common) as well as nausea, sleepiness, visual disturbances, mood changes, hallucinations, out-of-body experiences, and paranoia, he says.
Studies on ketamine for migraine are sparse, Cohen says. Though some show good outcomes, others have conflicting results, he says. Plus, ketamine can’t be studied with the gold standard for clinical trials: the randomized, double-blind, placebo-controlled study. (Ketamine has profound consciousness-altering effects, so a patient would likely know they are getting ketamine instead of a placebo).
Cohen believes it’s an appropriate medication for some patients; he is simply wary of moving too quickly.
“I think it needs to be studied better. People are using it indiscriminately and there’s definitely risks and side effects. So you need to actually be able to weigh the risks and the side effects – the risk-benefit ratio – to know the benefits better.”
Still, for some patients, says Cohen, the risk is worth the reward.
A New Start
It has certainly made a big difference for Safran.
“I’m grateful to be in a better place than I was and back in school doing something I love right now,” says Safran, who is studying to become a nurse.
It was her experience as a migraine patient that sparked her interest in nursing. “I love the idea of being able to work directly with patients because I know what it’s like to be on the other end.”
There were providers who made her feel dismissed, unheard, misunderstood. But there were others that went the extra mile.
“When various providers would spend the extra time listening to me, providing validation and understanding, that made such a difference to me. They went out of their way and helped clarify things or advocate it for me.”
And that, says Safran, is exactly the kind of care she wants to bring to others. “That’s why I wanted to go into nursing – so I could help advocate for people during the worst times of their lives.”
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