How A 'Party Drug' Paved The Way To Relief For Treatment-Resistant Depression

by Susie b Cross

It wasn’t too many years ago when those suffering from treatment-resistant depression (TRD) could find themselves ready to tap out, resigning themselves to a life spent lying prone on couches and beds. Those who earn the label “treatment-resistant” generally have failed to respond to two to three antidepressants, though I personally don’t know how many meds I tried before or after I was diagnosed with TRD. In my mind, I could have filled a jumbo popcorn bucket. Many of us will gobble down whatever the doctor will let us get our paws on, until we finally uncomfortably accept that, no, we might not be the best candidates for pharmacological interventions.

(Of note: I think TRD is a poorly-worded term. I know when doctors told me I had it, I kind of hopelessly shriveled. To me, it sounds like, “Welp, you’re gonna have to take this one on the chin, kid. You are most likely going to live a long and inescapably miserable life. Try Reiki again.”)

My therapist even suggested, in the most delicate way, that medicine might not be my savior. So I tried Transcranial Magnetic Stimulation (it didn’t work); and then I was on-track for the modernized version of ECT, which is in reality nothing like what we all saw on “One Flew Over the Cuckoo’s Nest.” But, honestly, the possibility of retrograde amnesia had me spooked.

So I started researching like crazy. Though my concentration was frazzled, I could thankfully still read pretty well. I studied every book I could find, looking for pieces of myself. (William Styron’s “Darkness Visible” is still my favorite memoir.) And I read the indisputable champion of all nonfiction on TRD, Andrew Solomon’s “Noonday Demon: An Atlas of Depression.”

In the midst of his depression, Solomon, who researched available treatments all over the world, travels to Senegal and participates in a sort of public exorcism. He ends up naked and covered in cockerel blood, then wrapped in ram intestines—and is offered a Coke to slake his thirst in between. At this point in my life, traveling to Africa seemed like a feasible option.

In walks ketamine, just soon enough to distract me from my interest in animal blood and entrails. It was pretty experimental for TRD at the time (according to the FDA, it still is) and not as accessible as I’d have liked. Though not as distant as Senegal, big city hubs were the norm for the IV treatment—and my mannequin, inert body was not going to make a trip anywhere unless someone strapped me on and piggy-backed me there.

The entrance of ketamine into the world of psychiatry was not a smooth one. Though its use was on-label as anesthesia, the public was wary of a “party drug” (yep, it’s the same “Special K” all the ravers were snorting in the ’80s) turned remedy for mental illness. What was next? Heroin for acne?

The other day I came out of my psychiatrist’s office, looked to the left and saw a door marked ESKETAMINE TREATMENTS. I was excited, since ketamine had finally made it to my rinky dink midwestern town. I was off-base. Esketamine is not exactly ketamine, though they do share similarities. Somehow I missed that, in 2019, this new drug was awarded the FDA’s seal of approval as an on-label treatment for unremitting depression. The U.S. government’s vote of confidence was essential. And thus, Special K’s sidekick went legit and entered the mainstream. (Unavailable in its generic form, esketamine has been branded Spravato by its maker, Johnson & Johnson.)

Thankfully, esketamine’s mode of delivery is a nasal spray versus ketamine’s intravenous route. Each treatment targets depression incredibly quickly, with some patients noting, in a matter of minutes, a mood shift.

This is a huge boon for suicidal patients who traditionally would have had to wait upwards of two weeks for an antidepressant to kick in—if it ever kicked in at all. Imagine how someone with TRD would react to such immediate mitigation. After being told they are “resistant” to treatment and, after sometimes waiting years, they are offered some relief and, finally, some hope. Adam Kaplin, M.D., Ph.D, psychiatrist with Johns Hopkins Medicine gets it: “For some people, esketamine therapy is revolutionary, giving them the chance to experience life without depression for the first time in decades.”

Too often, the world considers depression a protracted sadness, imagining that when we snap out of it, life—and our minds—will go back to “normal.” Well, that would be great, but unfortunately depression can damage our brains over time, causing deficits in “memory, executive function, attention, mood, and emotional regulation.” Amazingly, esketamine—unlike already-existing antidepressants—has neuroplasticity superpowers. What this means is that esketamine helps “heal” a sick brain. So, what we lost during our prolonged or acute depression might actually be recovered, at least partially, as we recover.

The impact of FDA-approved esketamine entering the psychiatric arena is humongous. “For the first time in 60 years, we have a new antidepressant therapy that isn’t just a spinoff of existing drugs,” explains Kaplan. For the first time in over half a century, we—the often-disregarded populations with TRD—are being seen and heard and helped.

I never did try ketamine—at some point (and with the help of an impressive and gargantuan drug cocktail) my TRD cleared. Plus, I have no reason (thank the lord) to seek esketamine out now. But, I don’t think for one minute that my TRD is not coming back.

If I continue to live where I am, I know I have an esketamine safety net about a mile away. And if anyone is near Sassafras Mountain, South Carolina or Altoona, Iowa (or hundreds of other cities), they will be near a treatment center as well. The future of esketamine (and its offspring?) is already here and there and everywhere. Badass esketamine is among us, ready if we need it; this comforting knowledge keeps a lot of us going. And ketamine, the “party drug,” paved the way.