While the FDA’s approval of the first ketamine-based drug for treatment-resistant depression is encouraging, there are still a lot of details to work out before Mass General can offer it as a treatment, says Cristina Cusin, MD.
“It’s a very complicated situation at the moment,” she says. “The practical details of how the drug will be delivered in a clinical setting are still very murky.”
Dr. Cusin is the director of the Ketamine Clinic at Mass General, where she has conducted numerous clinical trials to assess the effectiveness of ketamine in treating patients with treatment-resistant depression (TRD). At the MGH ketamine clinic, infusions and intranasal treatments are offered, however those are not covered by insurance.
Terms of Approval
On March 5, the FDA approved Spravato, a nasal spray developed by Johnson and Johnson that delivers esketamine, one of the two mirror image molecules that make up ketamine.
One of the most encouraging aspects of esketamine’s approval is that it’s the first treatment for depression that targets a neurotransmitter other than serotonin. The drug acts on glutamate, a neurotransmitter responsible for sending signals between nerve cells.
Under the provisions of the FDA’s approval, esketamine can only be administered in a clinical setting, and the patient needs to be monitored for two hours after each treatment to watch for side effects. These terms will pose some logistical challenges for providers and patients alike, Cusin acknowledges.
Providers will have to find space and staff members to monitor patients after treatment. Patients may have difficulty finding the time for a two-hour treatment each week, and it’s unclear how missing a week of treatment could impact the overall effect of the drug.
“What happens if you have difficulties and you can’t make it to the office on certain days? Would one’s mood worsen dramatically because he or she can’t get the medication at the right time?”
She can understand why the FDA is proceeding cautiously with the rollout, however.
“It’s a controlled substance, and in the midst of the opioid crisis, I would imagine the FDA wants to establish rigorous barriers to prevent diversion and misuse, and a registry to determine its long-term safety, because we just don’t have a lot of data.”
Questions also remain about how insurance companies will cover the cost of the drug and determine which patients quality for treatment. The cost ranges from $590 to $885 per treatment, which could add up to $30,000 to $50,000 each year, according to a recent STAT news article.
“Different insurers may have different takes and different regulations,” Cusin acknowledges. “So it’s not just a clinician opinion and patient’s wishes, but there is a third party deciding who is going to pay for this treatment and how much of it is going to be covered.”
Unanswered Questions and Long-Term Implications
As with any new drug, there are questions about the long-term effects of ketamine and how it may impact patients with co-existing medical conditions, Cusin says.
In all ketamine research studies, for example, the team has excluded participants who have a history of psychosis or a recent history of substance use disorder because they were unsure of how the treatment would impact those conditions.
There is also a broader question about patient selection, Cusin notes. “How many treatment failures are enough to quality for ketamine? It’s difficult to figure out in certain cases–do you go through three, five or 15 traditional antidepressant fails before going to ketamine, given the lack of long-term safety data 10 or 20 years out?”
Cusin also cautions that the drug is not a magical cure-all. In studies, approximately 40 percent of participants do not respond to the treatment. Her team does a lot of prep work to educate participants of the possibility that the drug won’t work and that they will continue to pursue other treatment options if it doesn’t.
Despite the caveats and questions that remain, esketamine’s approval gives providers a much-needed new approach to help patients with treatment-resistant depression, Cusin says.
“It’s great that the FDA approved it. It’s great that we have another option and that more patients will have access to it.”