Ketamine’s journey from party drug to Big Pharma blockbuster didn’t come easy after Johnson & Johnson’s depression drug Spravato got off to a slow start during the pandemic. But it’s now a bona fide triumph.
Sales of Spravato, which hit blockbuster status for the first time in 2024, grew by more than 57% last year to nearly $1.7 billion, J&J reported. CEO Joaquin Duato noted in a call with investors that more than 200,000 patients have been treated with the drug, which was approved in 2019 as the first of its kind for treatment-resistant depression.
Despite ketamine’s dark past as a highly addictive and dangerous psychedelic, Spravato’s formula, based on the drug’s chemical cousin esketamine, offers a fast-acting alternative to serotonin-based treatments. And while late-stage study results and clinical uptake have shown the drug’s effectiveness for certain patients, mental health professionals still approach its use with a dose of caution.
Ketamine was first approved by the FDA as a dissociative anesthetic in the 1970s for surgical use but was also being explored as a psychiatric treatment. The rise of antidepressants like Prozac in the 1990s slowed the trajectory for ketamine-based therapy.
Then came the next wave of interest in treatments using the psychedelic compound.
“The upswell around ketamine as a treatment in the 2010s was happening at the same time as the opioid epidemic, and people had concerns because ketamine has ulterior uses outside of medicine,” said Dr. Ben Yudkoff, a psychiatrist, Harvard Medical School instructor, and co-founder and chief medical officer at ketamine therapy clinic Lumin Health. “There’s a lot of healthy tension around how we talk about this in light of the fact that it has street uses, but it’s also helpful.”
Spravato’s approval has potentially helped pave the way to payer coverage for psychedelic treatments, while demonstrating how to ensure protections for patient observation and physician training, Yudkoff said.
With Spravato now making a sizable mark on the mental health landscape, clinicians are treading carefully to leverage the drug’s success without repeating industry mistakes from the past.
‘A perpetual balance’
Ketamine-based treatments like Spravato can be a hazard when abused, but still effective at treating depression.
“It’s a perpetual balance,” Yudkoff said, noting that clinicians administering a drug with psychedelic properties need to weigh both subjective experience on the part of the patient and objective medical benefit. “It creates a healthy discomfort and tension among providers as we grapple with walking in both worlds.”
J&J demonstrated Spravato’s superiority to placebo in a late-stage study. For clinicians now administering the therapy, the immediate impact on the patient tends to be an individual experience, which adds a level of nuance to the pharmaceutical equation.
“It’s the responsibility of the pharmaceutical company to promote metrics like durability and profundity of impact, response rates and scales to support evidence of a drug, and they’ve done a great job doing that,” Yudkoff said. “It’s important for us as academics and clinicians to take that primary mechanistic approach and think about some of the permutations and other elements, especially coming from the work of ketamine.”
About 30% to 40% of people will not get any benefit from Spravato, Yudkoff said.
Either way, with approved drugs like esketamine and other psychedelics in the pipeline such as psilocybin and 5-MeO-DMT, patient autonomy and participation is becoming a greater part of the conversation.
“A lot of the treatments coming out are pitching toward what the market demands, and so there’s an order of participatory control that a physician is managing on top of the objective benefit,” Yudkoff said. “At the same time, let’s not let vaulting enthusiasm dictate evidence-based practice — something is still only effective in accordance with the standards we have.”
Lessons from opioids
Spravato is now big business for J&J, and other pharma giants are keen to get in on the action. For example, AbbVie acquired a psychedelic major depressive disorder drug candidate from Gilgamesh Pharmaceuticals last year for $1.2 billion.
But real-world applications still need to be carefully considered beyond objective results, such as the implications at a larger scale when prescribers take the reins.
Physicians prescribing new medications like Spravato need to question the effectiveness and risk that accompany them, Yudkoff said, noting how the opioid epidemic was a prime example of how a treatment regimen can spiral out of control.
“It wasn’t that long ago that we saw the wanton prescription of opioid medications, the consequences of that, and then the healthy pullback and self-reflection of what we did wrong as a community,” Yudkoff said.
For ketamine, the comparison can’t be avoided. But done the right way with both scientific and real-world understanding, clinicians can achieve a balance that meets the needs of their patients without succumbing to the overabundance that characterized the impact of opioids.
“As a provider class, we need to focus on building trust and letting people know what the evidence is, collaborating more closely with the pharmaceutical company, who are in fact listening to us,” Yudkoff said. “It’s also important to appreciate [how] the insurance-based model enables accessibility and puts healthy restrictions to stay within the confines of the system.”
Treating patients with Spravato has as much to do with what happens during a doctor’s visit as it does with the effect of the drug, Yudkoff said.
“The purpose of the medication is not to enhance the moment, which is a substance use model, but to create long-standing changes,” he said. “Ultimately, it’s worth seeing what actually ends up helping people and how to make it safe.”
