- Once dismissed as a “party drug,” ketamine is emerging as a potential alternative treatment for depression.
- A growing list of academic medical centres now offer the drug, including Columbia University, which began offering ketamine to patients with severe depression this fall.
- Ketamine works differently from common antidepressants like Celexa or Prozac and has been called “the most important discovery in half a century.”
- Pharmaceutical companies, including Allergan and Johnson & Johnson, are also working on developing blockbuster antidepressants inspired by ketamine.
Ketamine, a drug once associated with raucous parties, bright lights, and loud music, is increasingly being embraced as an alternative depression treatment for the millions of patients who don’t get better after trying traditional medications.
The latest provider of the treatment is Columbia University, one of the nation’s largest academic medical centres.
Starting this month, Columbia joined a growing list of major medical centres offering ketamine infusions to patients with severe depression, for whom traditional antidepressants like Prozac or Celexa have failed.
Elsewhere in the US, patients can get ketamine at a smattering of private clinics, but not all of them are subject to the strict medical oversight that’s generally required of academic medical centres. In some cases, patients can also get the treatment by participating in research studies, but Columbia’s move helps make the treatment more broadly available.
Ketamine is not cheap, and it isn’t quick to administer. Because it’s given by way of an IV drip, the process can take between 45 minutes and two hours. Each session costs $US500 to $US750 (Columbia is charging $US650) and is not covered by insurance, because ketamine is only approved in the US for use as an anesthetic.
Patients given ketamine for depression are typically advised to get 8 to 12 sessions, bringing the total cost to as much as $US9,000.
Despite its hefty price, ketamine has been called “the most important discovery in half a century” for mental illness. The drug appears to engage a different part of the brain from traditional antidepressants, and its apparent rapid-fire effects may be especially useful for staunching suicidal thinking in people who are considering taking their own lives, experts say. Ketamine also has a long history of being used to prevent pain, which suggests to clinicians that it’s relatively safe.
“Ketamine is the real deal in that it’s a genuine pharmacologic agent that’s been used for a long time for anesthesia,” Jeffrey Lieberman, the chair of the psychiatry department at Columbia University’s Irving Medical Center, told Business Insider.
And while ketamine’s applications for mental illness are relatively recent, Lieberman is hopeful that the drug will eventually be more widely available to patients in need.
‘The most important discovery in half a century’?
Most antidepressants, from Abilify to Zoloft, work by plugging up the places where our brain takes up serotonin, a chemical messenger that plays a key role in mood. The result is more free-floating serotonin and, in some people, relief from a dark curtain of depressive symptoms. But as many as one in three patients fail to respond to the medications, and no new type of depression drug has been invented since then.
Those are the patients who experts say ketamine might help.
In those patients, it can be helpful to think of depression as akin to severe pain, Cristina Cusin, a psychiatrist at Massachusetts General Hospital and an assistant professor at Harvard University, told Business Insider this spring. When the pain gets so intense that it gets in the way of everyday activities – even something as simple as writing an email – patients can feel desperate enough to do anything to alleviate the suffering. But antidepressants take 4-6 weeks to work.
That’s not good enough for patients who need help now, said Cusin.
A growing list of providers offering ketamine
Large institutions are starting to embrace ketamine therapy.
On the West Coast, the University of California in San Diego began offering the infusions to select patients with severe depression in 2010. Kaiser Permanente started administering ketamine as part of a pilot program in Northern California for people who didn’t respond to other medications in 2015.
On the opposite side of the country, a handful of specialty centres recently began offering the treatments. They include Emory University, Yale University, and Massachusetts General Hospital, which began offering the treatments this fall.
Several other medical centres, including the Cleveland Clinic, the Mayo Clinic, and the Icahn School of Medicine at Mount Sinai, are administering the drug as part of ongoing research on ketamine and depression.
“The rapid antidepressant effects of ketamine in patients with severe, chronic, and treatment-resistant forms of this illness may represent a true medical breakthrough,” James Murrough, the director of the mood and anxiety disorders program and an associate professor of psychiatry and neuroscience at the Icahn School of Medicine, wrote in an October story for Scientific American.
Columbia University’s program is one of the first to not require patients to show a specific number of failed treatments for depression in the past. (At Kaiser, patients must show that they have tried at least three different antidepressants and failed to respond to each one.)
Still, Lieberman stressed to Business Insider that experts carefully weigh the benefits and risks before recommending the treatment to a patient, and they always advise people to try traditional medications first.
“We have to do a very careful history and if [someone has] a mood disorder, what’s their treatment been? Is the person genuinely unresponsive to standard treatments?” Lieberman said.
How ketamine works
Ketamine is believed to engage a different brain system from the one targeted by traditional antidepressants. It appears to act on key switches in the brain called NMDA receptors, which influence mood and help keep our brain’s synapses – the delicate branches that serve as the ecosystem for our thoughts – flexible and resilient.
Depression damages these brain switches. And while traditional drugs may help to rescue them over time using serotonin, ketamine appears to deliver its aid directly to the source, plugging up NMDA receptors like a cork in a bottle and nipping depressive symptoms quickly.
A spate of recent research supports this idea of how ketamine provides relief.
Last December, researchers working with depressed and suicidal patients concluded in a study that ketamine was better at curbing suicidal thoughts than a commonly used sedative. Most participants in the study, published in the American Journal of Psychiatry, said their moods began to lift within 24 hours of receiving the drug. In some people, those effects lasted more than a month.
Similarly, the authors of a 2012 review of four preliminary studies on ketamine in patients with severe depression expressed surprise at how rapidly the drug appeared to produce positive and precise results.
But ketamine also has several drawbacks, aside from its steep price tag.
Ketamine induces what many people refer to as a high. This includes feelings of being dissociated from one’s body and floating, as well as seeing bright colours and shapes. Some experts have suggested this could lead to issues with addiction.
In addition, ketamine’s side effects can include blurred vision, headaches, and increased heart rate. And clinicians aren’t yet sure how long ketamine’s anti-depressive effects last. While some patients appear to experience a complete alleviation of their symptoms after several weeks of treatment, others either fail to respond or only see improvement for several days or weeks.
Nevertheless, several clinics outside of established medical centres are also offering the treatments, and while some are legitimate, others are what Lieberman described as “scary” and “aggressive” in their marketing tactics.
“It’s not that ketamine shouldn’t be available – it absolutely should – it just has to be available in a legitimate and medically controlled and rigorous setting,” Lieberman said.
Ketamine is inspiring several attempts to create the next blockbuster depression drug
Ketamine is also inspiring research into other new depression drugs that work on the brain in a similar way. Homing in on this channel appears to provide depression relief that is better, arrives faster, and works in more people than existing drugs.
Allergan, the multinational pharmaceutical giant known for Botox and birth control, recently dove deep into research on an injectable depression drug called Rapastinel, which works on the same brain pathway as ketamine. San Francisco-based drug company VistaGen is working on a similar drug known only as AV-101.
Similarly, Johnson & Johnson submitted a nasal spray formulation of ketamine called esketamine to the FDA in September for its review. New York-based biotech company Seelos Therapeutics also has a nasal form of ketamine in its pipeline called SLS-002.
But research is still early, experts say.
“We are just scratching the surface of the mechanisms of action with ketamine,” Cusin said this spring.