For some, the drug ketamine can be a lifesaver. But recent shortages have made it hard to get

Samira Rostami has been getting massages for decades to relieve stress, but in the summer of 2021, a masseuse tried a new technique that would do the opposite of calming the body.

The masseuse targeted the joints around the base of her skull, pressing deeply into her spinal cord. The next day she was bedridden with fissures of pain radiating across her upper back as if someone was trying to tear her muscles in two. Over the next few months, the pain worsened such that she could no longer swallow pills or food. Barely able to hold her head up, she spent a year sustaining herself on meal replacement shakes.

“I was at a doctor’s appointment almost daily from Monday through Friday for about six months after the injury, begging anyone and everyone to figure out what was wrong with my neck,” Rostami, a communications professor in San Diego, California, told Salon in a phone interview.

It took seven months after her injury for doctors to diagnose her with complex regional pain syndrome (CRPS). Although this condition varies with each patient and some achieve remission, CRPS has been called the most painful condition, usually affecting hands or feet and spreading throughout the body. The pain can be so intense that some patients opt to have an affected limb amputated. Opioids or other analgesics often don’t work against it but one treatment that has shown some promise is ketamine, an anesthetic administered through infusions that can have psychedelic properties.

Since May of 2022, the ketamine doses Rostami receives monthly were one of the only things she has found that can improve her condition. But this year, it became increasingly hard to find when a national shortage caused her clinic to cut down on her appointments and eventually cancel some until they could restock. For Rostami, that meant finding an alternative clinic that didn’t take her insurance or going without treatment.

“When there’s a national shortage, they have to cut back on how many treatments you can get,” Rostami said. “It just depends on how much pain I’m in that month, if I want to spend $2,000 for an infusion, or if there is availability in San Diego and I can find a clinic.”

Originally approved by the Food and Drug Administration (FDA) in the 1970s as a local anesthetic, ketamine is also a dissociative psychedelic that can produce dream-like effects or out-of-body experiences. It targets a chemical messenger in the brain called glutamate that regulates memory, cognition and mood.  

Although it has not been approved to treat mental health conditions or chronic pain, doctors have increasingly been prescribing ketamine off-label for mental health conditions like treatment-resistant depression and pain conditions like CRPS. Some patients report negative side effects and don’t react well to it, but others undergo profound experiences in which they can see their past trauma in a new light, find long-sought pain relief or leave behind crippling anxieties. 

One in every six Americans experiences depression and up to one in three of those people won’t respond to first-line treatments like selective serotonin reuptake inhibitors (SSRIs). Meanwhile, the opioid overdose crisis has led physicians to cut back on writing pain medication scripts with the unintended consequence of leaving many patients with chronic pain with even fewer treatment options. Some patients are desperate for a way to relieve their psychiatric or physical pain, and some doctors are frustrated at not being able to help them. Ketamine is filling this treatment gap for many in both treatment spaces.

Nancy, a mother of three who runs an animal rescue center in Houston, Texas, who asked to use only her first name, started going to a ketamine clinic to treat her depression in 2021. After it worked for that condition, she decided with her doctor to start ketamine in a different dosage to treat her fibromyalgia, which has put her in debilitating pain for 30 years. However, the latter is not covered by her insurance and is going to cost her $1,350 per treatment, a cost which “has to be worth it,” she said.

---

Want more health and science stories in your inbox? Subscribe to Salon’s weekly newsletter Lab Notes.

---

“At this point, nothing else is helping and I am not able to be the mom I want to be and do the rescue work I want to do,” she told Salon in a phone interview. “Life is pretty miserable right now with this much pain, so I feel like I have to try something.”

Like many practitioners in what is sometimes called the “psychedelic renaissance,” what led Dr. Steven Radowitz, the chief medical officer of Nushama ketamine clinic in New York, to psychedelic medicine was frustration that many patients had stopped responding to treatments he was prescribing, as well as a belief that psychedelics had the potential to address the underlying issues related to mood disorders that could facilitate deeper healing.

“What this does is it opens people up to see life in a different way, a more open way,” Radowitz told Salon in a video call. 

In 2019, the FDA approved Johnson & Johnson’s isolated formulation of the ketamine molecule, esketamine (sold under the brand name Spravato as a nasal spray), for treatment-resistant depression after it was shown to improve symptoms in clinical trials. (Esketamine is a slightly different from racemic ketamine that is typically given at clinics.)

This led to a dramatic increase in the number of clinics offering ketamine therapy for conditions for which it is not approved, even though the same level of rigor hasn’t been applied to research examining ketamine for mental health conditions, said Dr. Gerard Sanacora, a psychiatrist at Yale University who studies ketamine. 

“There’s just really a lack of good data demonstrating the safety and the efficacy of those forms of treatment,” Sanacora told Salon in a phone interview. “That doesn’t mean they’re not safe or not effective, but we just really don’t know.”

Yet there are some promising results from scientific research. One study in the Journal of Clinical Psychiatry found ketamine infusions improved suicidal ideation, depression and anxiety, although that was a retrospective chart review and not a randomized clinical trial. Another study found ketamine reduced suicidal ideation within three days, but it’s unclear whether these effects were upheld in the long term. Similar findings were published last week in a meta-analysis looking at ketamine as a treatment for post-traumatic stress disorder. A fourth study published in June in the New England Journal of Medicine found ketamine worked just as well as electroconvulsive therapy among patients with depression.

In 2018, three professional medical organizations including the American Academy of Pain Medicine published guidelines for using ketamine infusions to treat chronic pain, citing a few randomized controlled trials that showed it was effective, although the “level of evidence varies by condition and dose range.”

However, some in the medical community fear the cart has gone before the horse with the number of ketamine clinics that have popped up in recent years. In a study published last week in JAMA Network Open, a survey of 17 ketamine centers in Maryland found seven failed to disclose any potential adverse effects and one falsely claimed ketamine was FDA-approved for depression and was not addictive. (Ketamine can be addictive, but the risk is generally considered low, especially when given under clinical supervision.)

Dr. Padma Gulur, a pain management specialist at Duke University studying ketamine, said clinics need to have specific protocols in place: ensuring patients are medically evaluated before treatment to reduce the risk of a bad reaction, for example, and monitored after dosing because of ketamine’s sedative effects.

“It has potential, but it is also not without risk,” Gulur told Salon in a phone interview. “Even if it gives you some short-term gains, it may not give you long-term benefits, at best. Or, potentially, there may be long-term harm we are not aware of yet.”

Perhaps due to increased demand, manufacturing or supply chain issues, racemic ketamine used in these infusions has been in shortage since 2018. In an October survey of 126 ketamine providers across the country conducted by the American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP3) — which has issued some best practices for ketamine clinics to follow — 61% had to cancel appointments due to the shortage, said ASKP3 president Dr. Sandhya Prashad.

“Some people have had to delay treatment, which may not sound like a big deal, but for patients who have suicidality, it’s a very big deal,” Prashad told Salon in a video interview.

Dr. Brent Turnipseed, the medical director of a ketamine clinic Roots Behavioral Health in Austin, Texas, said the shortage has forced his team to turn toward compound pharmacies to fill their supply so patients are not left out to dry.

“We’ve been pivoting quickly to try to figure out any option we can for our patients, but it’s been stressful,” Turnipseed told Salon in a phone interview.

Last month, the FDA issued a warning acknowledging the increased interest in compounded ketamine products such as oral tablets called lozenges, outlining the risks of using a drug like ketamine without the supervision of a healthcare provider. In addition to sedation and dissociation, long-term use of ketamine can lead to urinary problems as well as psychiatric events, the agency stated. 

“Consumers should be aware that compounded drugs pose a higher risk to patients than FDA-approved drugs because compounded drugs do not undergo FDA premarket review for safety, effectiveness or quality,” a spokesperson told Salon in an email.

The agency did not respond to questions about what was causing the shortage and what was being done to ameliorate it. During the pandemic, federal agencies loosened regulations that allowed for substances like ketamine to be prescribed via telehealth appointments, which could be affecting supply. 

One of the most common safety concerns highlighted by the FDA’s adverse event tracker for ketamine is drug “misuse,” but some evidence suggests recreational ketamine use in the U.S. remains low, with fewer than 2% of American adults having used ketamine in their lifetime, according to the Substance Abuse and Mental Health Services Administration’s 2022 National Survey on Drug Use and Health. The University of Michigan’s 2022 “Monitoring the Future” study, which looks at drug use among high school students, also showed no increase in the portion of students having tried ketamine since 2004. In the clinical setting, it is administered by practitioners and not intended to leave the office.

Although there did seem to be a ketamine clinic boom during and after the COVID-19 public health emergency, that seems to be dying down, Prashad, of ASKP3, said. This year, two major chains of ketamine clinics, Field Trip and Ketamine Wellness Centers, abruptly shut down, leaving many patients scrambling for other options. The situation was especially dire as many patients had come to rely on the treatment to maintain their mental health. In the ASKP3 survey of ketamine providers, 8% said the shortage caused them to shut down or consider shutting down their clinic, further reducing access to a treatment that has provided many with relief when other therapies don’t work.

“I have witnessed it with my own patients and with my own eyes that this is truly a life-saving treatment for some people,” Sanacora, at Yale, said. “But the potential for things to go wrong is real and that really does need to be mitigated.”