In a popular and public move, the United States’ Federal Drug Administration recently approved intranasal esketamine, one of the components of the psychedelic ketamine, for treatment-resistant depression. The nasal spray costs nearly $900 per dose—or roughly $7,000 for the first month of treatment, and each treatment takes at least two hours in a clinic. (It has yet to be decided how much of the cost insurance plans will cover.)
Esketamine can be unwieldy to use and carries a number of significant potential side effects. Shockingly, it was no better than placebo in two of the three short-term Phase-III studies submitted to the FDA for approval.
But the biggest problem at hand is not the drug itself. It’s the fact that instead of representing a revolution in mental health treatment, as it has been touted to do, esketamine is not a breakthrough at all. It’s just a way for pharmaceutical company Johnson & Johnson to make a significant profit off gullible insurance companies and vulnerable patients.
Generic Ketamine Works
Generic ketamine is available for a fraction of the price of esketamine, has been shown to work—and work safely—in small-scale single-dose and multidose trials for treatment-resistant depression, can be administered in a variety of ways, and has already been used off-label for decades to treat thousands of patients with depression and suicidality.
It’s currently difficult, if not impossible, to provide generic ketamine treatment in public clinics, even to patients who need it, because there haven’t been any large-scale, randomized trials, both with and without psychotherapy. Without these trials, and resources, physicians can’t be reimbursed by insurance companies for ketamine treatment like they will be able to do with esketamine.
Ordinary ketamine is a racemic medication, meaning it is made up of two molecules that are mirror images of each other. Because ordinary ketamine is generic, Johnson & Johnson simply isolated one of the two molecules in regular ketamine so that it qualified as “new.” The reality is that we don’t know whether esketamine is more or less effective than regular ketamine because there have been no head-to-head trials between the two. Johnson & Johnson only tested esketamine against a placebo, likely because they feared esketamine might actually perform worse than the generic version.
As many critics have pointed out, this strategy has become the bread and butter of drug development in the United States today. Largely because of the influence of pharma on the FDA itself, our drug approval process rewards copycat variation of already-available drugs instead of truly innovative pharmaceutical design.
When Psychotherapy Is Missing
The trials for esketamine also reveal a larger issue in the field: they de-emphasized the importance of psychotherapy while focusing solely on its chemical effects. The most effective treatment strategy for treatment-resistant depression is intensive psychotherapy along with the use of medication, but the FDA esketamine trials didn’t include therapy at all.
Getting insurance companies to pay for psychotherapy is already difficult, and without it as part of the protocol, they will likely offer no reimbursement for patients interested in receiving a psychotherapy session after their esketamine dose in order to process the experience.
Our colleagues who offer ketamine-assisted psychotherapy say that this is a vital part of the process. One such session can require upwards of three hours of one-on-one treatment in order to prepare patients for the experience, take care of patients while they are under the influence of ketamine, and then integrate the effects afterwards. Ironically, insurance companies would save more money paying for generic ketamine-assisted psychotherapy rather than esketamine treatment alone, as the former is both cheaper than the latter and can lead to long-term remission of symptoms.
Alternatives
Private ketamine clinics currently do exist, but they have to fight the stigma of the drug, and sporadic cases of malpractice. Some private clinics do not properly screen patients prior to initiating treatment and often charge outrageous sums of money—one reason that both patients and medical systems have been hesitant to implement it more widely. Those clinics that are providing ketamine responsibly, however, offer a potentially lifesaving treatment for patients living with depression who have exhausted all other available options.
Although there are no quick fixes for the broken drug-development and approval process that led us to esketamine, it is possible to take concrete steps to address the most glaring problems. Insurance companies and the FDA ought to require head-to-head study designs of clinical trials to investigate generic and patented medications. Additionally, current research on medication-assisted psychotherapy with other psychedelic substances such as MDMA and psilocybincan serve as a model for future research that explores ketamine-assisted psychotherapy, instead of the drug alone.
While Johnson & Johnson rakes in the profits from esketamine, patients dealing with depression and trying to navigate our struggling mental health system will bear the cost. Fostering the development of mental health treatments that are novel, effective, and affordable will require a critical examination of the undue corporate interests that drive drug approval in American psychiatry today.
Dr. Michael D. Alpert is a psychiatrist and clinical faculty at Harvard Medical School. He is also a therapist with the MAPS Clinical Study of MDMA-Assisted Psychotherapy for PTSD.
Dr. J. Wesley Boyd, MD is a psychiatrist and associate professor at the Center for Bioethics at Harvard Medical School.
Dr. Marco A. Ramos is a psychiatry resident at Yale University.
