The New Medicine of the Mind

Ketamine and Other Psychedelics Are Changing Mental Health Care

New treatments offer hope for those suffering from long-term depression.

By Megan McDonald January 3, 2023 Published in the January-February 2023 issue of Sarasota Magazine

This story contains a discussion of suicide. If you or someone you know is in crisis, text or call 988 to reach a trained mental health counselor. The service is free, confidential and available 24 hours a day.

It was a dark, clear night in early spring when my phone rang. I’d just finished taking my dogs out—rubbing my hands together to keep warm as my breath created small white clouds in front of me—and a constellation of stars glittered overhead, the light a contrast to the skeletal trees whose fingerlike branches stretched toward them.

As I came inside, I glanced down at the screen and I saw that it was my husband, Rob, who was working overnight shifts at his job in Pittsburgh, where we’d recently moved. We usually texted each other throughout his shift until I went to bed, but he didn’t often call.

When I picked up the phone, I figured he’d forgotten to tell me something—a funny anecdote or maybe a reminder to pay a bill, the kind of thing that becomes part of the fabric of your life when you’ve been together for 10 years.

What I didn’t expect was to hear his voice shaking. In a low, urgent tone, he told me he’d driven to his workplace and prepared to turn left into the parking garage like he always did. Then he’d looked up at the rooftop and had become consumed with thoughts of jumping off it. He’d somehow managed to pull himself together and go into work, but the throb of anxiety and the fear of the intrusive thoughts kept building until he’d called me.

“Come home now,” I said. “Tell your supervisor you’re sick. Leave your stuff in your locker and we’ll get it tomorrow.”

That was more than a year ago. We never went back for Rob’s things, and he has never been able to return to work.

At first, we thought his crisis was situational—and temporary. The previous two years had been intensely stressful: We’d moved to Pittsburgh in spring 2019 and my dad was in and out of the hospital and rehab for alcoholism all that year. At the same time, Rob’s sister, who has both physical and intellectual disabilities, was diagnosed with ovarian cancer and had to undergo months of chemotherapy and a hysterectomy. (This after undergoing a mastectomy and chemo for breast cancer in 2017.) In 2020, we bought a house—and our inspection took place the day before everything shut down due to Covid-19. We moved in during lockdown. Later that year, like many others, we adopted a pandemic puppy who, like all puppies, required an intense level of training and supervision. And Rob began working overnight shifts at his job before being transferred to another department, which meant he had to get on a schedule none of us were used to.

It made sense that he’d be reeling from all of this, I thought. He needed a break.

Plus, the Wellbutrin he’d been taking for years had never worked that well. Maybe he needed a new med, too.

But what I thought would be a month-long, maybe six-week, break turned into months of time when Rob couldn’t get out of bed. He didn’t want to shower or do any kind of basic self-care. When he wasn’t in a depressed state, he was deeply anxious. He’d start tapping and pacing if we had someone scheduled to come to the house or if he thought he might have to run an errand. A routine trip to Lowe’s would send him spiraling, his breath catching in his chest. He’d have to sit in the car for up to half an hour to calm down enough to drive home.

Luckily, the therapist he’d started seeing through work was paying attention, and when we told her he needed to see a psychiatrist and get on a new medication, she helped us schedule an appointment at a local practice within the week. Rob and I both breathed a sigh of relief.

“You’ll get on a new medication and continue therapy and it’ll be fine,” I told him.“This is just a blip.”

What happened instead was a long and winding journey through weekly therapy and multiple tries with selective serotonin reuptake inhibitors that led to an option neither of us had even heard of: weekly treatments with a hallucinogenic drug that’s been shown to have powerful antidepressant effects, but is still on the fringes of psychiatry.

It’s called ketamine.

Ketamine has been in the news lately because of its ability to relieve depression in people who are classified as “treatment-resistant”—that is, people who don’t respond to traditional medications like Zoloft, Prozac, Paxil or Effexor. Traditionally used as an anesthetic, ketamine’s street name is “Special K,” and it’s known for its hallucinatory effects.

For psychiatrists, those hallucinatory effects are significant, because research shows that while patients are under the influence of ketamine, the brain rewires and regenerates itself—repairing damage from mental wear and tear, like depression and trauma.

“As recently as 2003, the belief was that the brain didn’t repair itself—that there was a static level of growth after adolescence, but that’s just not what the truth is,” says Dr. Joshua Palmer, a psychiatric nurse practitioner who is also an associate professor at the University of Pittsburgh’s School of Nursing. He runs an esketamine clinic at Pittsburgh’s P.K. Mullick MD & Associates. (Esketamine, which is approved by the U.S. Food and Drug Administration, is made from the ketamine molecule and is considered a more potent form of the drug. Full disclosure: Palmer is also the physician treating my husband.)

Dr. Steven Reichbach, an anesthesiologist who runs Sarasota’s Reichbach Center for Ketamine, Medical Cannabis and Psychotropics (formerly the Gulf Coast Ketamine Center), says that ketamine jumpstarts chemical changes in the brain that lead to physical changes.

“Trauma and depression mess with your brain,” Reichbach says. “They eat away at dendritic spines [which help transmit electrical signals to neurons]. The brains of patients who have been through extensive trauma look different. Ketamine strengthens those dendritic spines and improves synapses, and, unlike marijuana, changes continue to occur even after the drug is out of the system. It’s a sustained antidepressant.”

Some patients who undergo ketamine therapy experience an almost unbelievable level of relief. “I’ve treated people who have been depressed for so long that they literally have forgotten what it’s like to not be depressed,” says Palmer. “They had little to no expressional ability and were so depressed it was almost traumatic. But within a week or two of treatment, those patients were smiling and talking and having nonverbal expression again.”

This is especially significant because research shows that between 29 and 46 percent of depressed patients fail to fully respond to traditional medications, and 19 to 34 percent don’t respond to medications at all. That’s staggering when you consider that an estimated 21 million American adults have experienced at least one major depressive episode—and that drug overdoses hit record levels in 2021 and suicide rates were 30 percent higher in 2020 than they were in 2000, according to the Centers for Disease Control and Prevention.

So why aren’t more practitioners using ketamine—or advocating for its psychedelic cousins, like MDMA, LSD and psilocybin, which have similar effects on the brain?

“There has been half a century of work to change cultural attitudes about psychedelics from fear to hope,” says Dr. Rick Doblin, the executive director of the Multidisciplinary Association for Psychedelic Studies, known as MAPS. Doblin holds a Ph.D. in public policy from Harvard University and is a New College of Florida alum. He credits his time at New College for opening the door to his career in psychedelics. MAPS was originally headquartered in Sarasota before it relocated to San Francisco.

“For a long time, there was zeal for the War on Drugs,” says Doblin. Now, “there’s a general sense that the War on Drugs was a failure, that it was all about persecuting minorities. In art and movies, you see psychedelic imagery all the time. Marijuana has been legalized and the culture is not falling apart.”

Doblin, whose research focuses on MDMA, believes that the medicalization of psychedelics isn’t far off. “I think that in 2024, there will be FDA approval for MDMA-assisted therapy for post-traumatic stress disorder, then psilocybin will be approved two years later. But it’s the success stories people tell that’s really going to change attitudes toward these substances. A dramatic transformation took place when Sanjay Gupta aired his weed series on CNN. The stories about how marijuana helped provide relief to children with epilepsy changed people’s minds. Stories like that accelerate the cultural acceptance.”

The author's husband Rob.

The author's husband Rob.

Image: Laura Mares

There are two types of ketamine treatments: ketamine infusions, which are administered intravenously, and Spravato, or esketamine, which is administered through the nose. Spravato has been approved by the FDA for use in treatment-resistant depression in conjunction with an oral antidepressant, like Effexor. Spravato can only be given after a patient has not responded to at least two traditional antidepressants, and both treatments are administered under the supervision of a physician.

At the Reichbach Center, ketamine infusions are delivered in a six-session package. Reichbach and nurse practitioner Lolita Borges monitor each patient’s blood pressure, pulse oximetry and heart, and administer the infusions based on the patient’s weight. From there, the dosage is adjusted based on the patient’s response. “As long as the patients tolerate it, we can keep bumping up the dose,” Reichbach says. “The sky’s the limit to try to elicit the positive response we’re looking for.”

Unlike ketamine infusions, Spravato is administered in specific dosages, using a nasal sprayer—56 milligrams to start, which can then be increased to 84 milligrams or higher as needed.

When Rob began taking Spravato at Palmer’s clinic in March 2022, he received treatments twice a week, in two-hour sessions, for eight weeks. Now he’s graduated to receiving it once a week. He self-administers the Spravato, snorting it up each nostril as Palmer supervises, with five-minute breaks between each dose. Then he leans back in a recliner, closes his eyes and drifts into a dreamlike state. Palmer checks his blood pressure three times: once before the treatment begins, once about 45 minutes in and once at the end.

“When it really kicks in, it feels like my teeth go numb,” Rob says. “I relax, and the darkness of having my eyes closed becomes like a lava lamp, with colors blending into each other from all directions.”

He tells me that he likes to untangle problems or reframe specific situations, too. “I thought about how everything changed for me when I moved to Florida from New York and then to Pittsburgh, and everything that turned out well,” he says, “and how thinking about ‘what-ifs’ from the past doesn’t make sense anymore.

“Or,” he says, “one time I had a song stuck in my head, so the lava lamp sensation played over the song, like I had my own light show.”

As an observer, I’ve started to think of the treatment like a quick flight from Pittsburgh to Boston: You taxi and ascend for half the time as the Spravato kicks in, and then you descend and taxi for the other half while it wears off. Rob isn’t allowed to eat two hours before the treatment or drive for the rest of the day afterward. He tends to sleep for several hours after we get back home, but any wooziness generally wears off by dinnertime.

Here’s the best part: He says he felt the depression start to lift significantly after four treatments—specifically after his dose was increased from 56 milligrams to 84.

“On a scale of one to 10, the depression has gone from a nine or a 10 to a two or a four,” he says. “There are still bad days, but more livable. I think my mindset of replaying past events and reframing the way I think about the outcome—even if it’s an outcome that’s not what I expected or wanted—has been a big step, too.”

Reichbach says his patients typically enjoy the infusions and experience a “warm, comforting, transformative” experience, with many reporting an improvement in their depression with just one dose. “The science really reveals that the physical changes in the mood centers of the brain start to happen almost immediately,” he says. With the infusions in particular, “you can follow the ketamine on blood-flow scans and [magnetic resonance imaging] in real time, and see how quickly it starts to take effect. It’s so much quicker than oral antidepressants, which can take weeks.”

After the first six treatments, Reichbach typically schedules a follow-up “booster.” Once he gets a grasp on how long a patient feels relief, they discuss future treatments. Both Palmer and Reichbach emphasize the need for counseling as patients adjust to a new reality in which their depression has faded.

“We’ve had to do a lot of therapeutic work with people to desensitize them from having a panic attack whenever they have a normal low mood,” Palmer says. “It’s hard to trust a normal range of emotion when you’ve been depressed for so long.”

There are downsides. Cost is a huge factor. The Reichbach Center charges $3,300 for six infusions, which works out to $550 per session. Some insurers will reimburse a percentage of the cost, but that’s still a significant investment up front—especially since, according to the CDC, 8.7 percent of people who have incomes below the poverty level report severe psychological distress.

Spravato, meanwhile, is covered by insurance and offers a savings program that can significantly reduce the cost of the drug, but there is debate about whether taking it intranasally is as effective as intravenously. For example, if you’re experiencing allergies on the day of your treatment, the drug may not make its way through the lining of the nasal passage and into the bloodstream as effectively as it might on another day. Spravato also hasn’t completely alleviated Rob’s intense anxiety, which spiked in 2021, and triggered obsessive-compulsive disorder behavior and, for several months, an inability to even leave the house. MAPS’ Doblin wonders how much more effective both treatments could be if they were offered in conjunction with talk therapy, like MDMA is. “The more therapy your husband does with the Spravato, the better,” he tells me.

Then there’s the way we think about mental health in this country in general. Ketamine and other psychedelics are still fringe treatments, and Palmer says there needs to be a major shift in the way we think about treatment-resistant depression—a term he bristles at, because he thinks it implies the patient is at fault—and depression in general.

“We need to stop blaming patients for being treatment-resistant,” he says. “We need to start thinking about depression as a heterogenous pathology. It’s not just about serotonin. In the past five years, there’s been a lot of research showing that depression is not a homogenous illness. There’s a whole interplay of other pathologies—like malfunctioning immune systems, or an abnormal hypothalamus or pituitary pathway—that come into play.”

Environmental factors affect outcomes, too. In his landmark book The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma, Bessel van der Kolk writes, “Traumatized people chronically feel unsafe inside their bodies: The past is alive in the form of gnawing interior discomfort. Their bodies are constantly bombarded by visceral warning signs, and, in an attempt to control these processes, they often become expert at ignoring their gut feelings and in numbing awareness of what is played out inside. They learn to hide from their selves.”

In my husband’s case, unprocessed trauma from childhood coupled with the way his brain is naturally wired led to his crisis in 2021. But in looking back over the course of his life, the symptoms of his depression and anxiety manifested in a host of different ways—from stomach problems as a child to migraines as a teenager and adult. Scopes snaked through his body to evaluate potential gastrointestinal issues; he visited neurologists to try to diagnose the cause of persistent migraines. Knowing what we do now about the nature of his depression and anxiety, it’s not surprising that he never found a satisfactory diagnosis for his symptoms.

“I remember lying down on the floor when I was 5 and out shopping with my mom because I didn’t want people to see me,” Rob says. After recovering from an injury that temporarily sidelined him from playing baseball, he never returned to the ballpark for the same reason—the anxiety of being seen. As an adult, he told me, he felt like he was having a panic attack every day. He was convinced he was going to die when he turned 27. When he didn’t, he just learned to deal with the panic—to put on a happy face even when he felt claustrophobic in his own body.
Still, I never would have known. He exerted so much effort trying to seem fine for so long that he’d fooled everyone—his friends, his family, me.

So what’s next? For Rob, the hope is that he continues to respond to the Spravato treatments as he works on his anxiety in therapy and, eventually, returns to work. “I hope the Spravato will continue to lower my depression,” he says. “I’m not sure it’s ever going to go away, but I want it to be as low as possible.”

Palmer says he hopes that those in his field will continue to become more open—both to treatments like ketamine and other psychedelics, as well as to the ever-evolving science of depression and mental health. “Something else is happening here,” he says. “I think that as the more moralistic views on medications change, we’re going to be more open, in general, to these treatments.”

Reichbach agrees. “There’s a lot of hopeful data that’s coming out,” he says. “To me, it’s about getting the word out that these treatments are available right now. I see six to 12 patients per day. The downside is almost nil, but the potential upside can be quite profound.”

Illustration by Jean-François Podevin

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