Up to one-third of adults with major depression battle symptoms such as persistent feelings of sadness, trouble sleeping, fatigue and suicidal thoughts that don’t respond to treatment. Yet there’s been very little new on the market since Prozac revolutionized the treatment of depression in 1988. Until now. This past Tuesday, the Food and Drug Administration approved the nasal spray esketamine as the first new type of treatment for depression in over three decades.
“It’s quite possibly the biggest advance for mental health in the past 50 years,” says Gerard Sanacora, M.D., director of the Yale Depression Research Program in New Haven, Conn. “It truly offers hope to people who have not responded to classical standard antidepressant treatments.”
There are three main reasons, he says: First, it seems to be effective in cases where other standard antidepressants like sertraline (Zoloft), bupropion (Wellbutrin) and duloxetine (Cymbalta) have failed. Second, it acts very rapidly. “We used to tell our patients it could take weeks or even a few months before they would begin feeling better, and now this offers potential benefits within hours or days,” he explains. Finally, it’s a completely new way of treating depression. “Almost all of the other antidepressants on the market target two main neurotransmitters: serotonin and norepinephrine,” Sanacora says. These two neurotransmitters, in turn, activate another neurotransmitter, glutamate, which is what boosts your mood. Esketamine instead works directly on glutamate, which is why its effect is almost immediate.
On the downside, the data on the effectiveness of esketamine for those over 65 is less encouraging. (More on that below.) And there are still some concerns related to the fact that it is closely related to ketamine, a drug typically used in anesthesia that rode to fame in the 1980s and 1990s as the party drug “Special K.” “There are definitely concerns about addiction and abuse,” says Amit Anand, a psychiatrist at the Cleveland Clinic who has been studying the use of ketamine for depression for 20 years. Because of this, esketamine will only be offered in doctor’s offices or medical clinics, under close supervision.
Here’s what you need to know:
Esketamine is not as effective in those over 65. Company data submitted to the FDA for approval, based on more than 1,700 adults with treatment-resistant depression, found that more than two-thirds of those who took esketamine (brand name Spravato) along with a new oral antidepressant experienced significant relief of symptoms within four weeks, compared with only about half of those who took a placebo. They were also less likely to relapse over the long term.
But the data among people over 65 is less strong. While the older adults did report improvement, it wasn’t statistically significant. “It appeared that people who had an onset of depression later in life may not have responded as well,” says Sanacora, who was one of the study’s investigators. “One thought is that later-in-life depression is different from depression that begins earlier, because it has a different neurobiology. It’s due to vascular changes.” But since it can affect cognition and perception, it may not be the best drug for older adults anyway. “You really need to weigh the potential risk-benefit ratio a little differently than when you treat a younger person,” Sanacora says.
It’s not a first-line drug. “People are flooding our offices with calls saying that they want this, but it’s not the treatment for just anybody. It’s for people who have not responded to standard antidepressants,” Sanacora explains. You need to have tried at least two antidepressants during your current episode of depression, without success. And even when you do take this nasal spray, you have to take a standard antidepressant with it, as well as engage in other treatments such as talk therapy, he adds.
There are some pretty serious side effects. Spravato will come with a black box warning, the strictest safety warning put in the labeling of prescription drugs by the FDA. The most common side effects include disassociation (having trouble thinking), dizziness, nausea, vertigo, anxiety, feeling tired, increased blood pressure, vomiting and feeling drunk. You have to stay in your provider’s office for at least two hours after getting the dose, and you can’t drive for 24 hours. “There are definitely changes in cognition and perception, and people who experience it say it is pretty weird — and in some cases, even a little frightening,” Sanacora says.
Cost is definitely a concern. Unlike, say, generic Prozac, which you can often find online for as little as $1.50 for a one-month supply, the first month of therapy on Spravato is expected to cost between $4,720 and $6,785 before insurance, rebates and discounts. (After the first month, the price drops to between $2,360 and $3,450.) “That comes to about $500 to $800 per dose, making it more on par with other interventional treatments such as electroconvulsive therapy [ECT] or transcranial magnetic stimulation [TMS],” Sanacora says. But if you’re strapped for cash, there may be a loophole for your doctor to consider, Anand says. As he notes, your doctor could conceivably administer an IV dose of ketamine, which has the same effects but is considerably cheaper.