Nothing seemed to treat their depression. Then they tried ketamine.

But after working out at his home gym on a recent July weekend, Anthony, a criminal defense attorney in Richmond, found himself serenading his three yellow labradors with 1980s hair band tunes. And it wasn’t an act.

Anthony joked about the impromptu show as a nurse at MindPeace Clinic in Richmond prepared the treatment he credited with his newfound mental well-being: ketamine. The psychedelic, used in medical settings as an anesthetic — and illegally as a party drug — is considered to be a promising but experimental mental health treatment. In a year-long evaluation of more than 400 patients, including Anthony, at three MindPeace ketamine clinics in Virginia, researchers found a significant reduction in symptoms of depression, according to a study published in the Journal of Clinical Psychiatry on Monday. Largely consistent with past studies, 72 percent of patients saw improvement in their mood and 38 percent were symptom-free after 10 infusions.

Ketamine for depression: What it feels like and who it can help

While the study has limitations, the findings appear to illuminate how ketamine could offer more than just brief relief to people whose depression is resistant to other medications. For many of the clinic’s patients who spoke to The Washington Post, the drug’s achievements have been life-changing. A retired hospital technician wondered about the career he could have had if he had been able to look people in the eyes during conversations, which he can now. A teenage boy cracked jokes with his mother. Anthony, who said he never goes for a walk, finally stepped out onto the street of his cul-de-sac.

“All of a sudden, you wake up and realize what you haven’t been feeling for 15 years,” he said.

Researchers said the study could offer a greater understanding of the drug’s long-term potential for treating people with depression, and more hope amid a mental health crisis that has worsened during the coronavirus pandemic. Ketamine is just one of a variety of psychedelics, including “magic” mushrooms and ecstasy, that people are turning to for relief amid a greater public acceptance and growing field of research.

Patrick Oliver, the study’s lead researcher and the medical director of MindPeace Clinics, said ketamine therapy could become a mainstream solution to depression and potentially other mental disorders that have long been undertreated. Nearly 46,000 Americans died from suicides in the United States in 2020, according to the National Center on Health Statistics.

“It’s an epidemic, and it’s been going on forever,” said Oliver, a former emergency room physician. “And we’ve found a medication that literally costs pennies to make and is fixing these patients.”

Experts say that ketamine shouldn’t be considered the first option for people with depression or suicidal ideations, given the other medicines and therapies that have been proved effective. The study, conducted by the ketamine clinic on a self-selecting group of patients, has its limitations. Suicidal ideations decreased at least 85 percent after 15 infusions, researchers found. But the study’s authors acknowledged that there is no system to track adverse events and side effects among ketamine patients. Nurses followed up with patients by phone after their treatments and recorded two suicide attempts. Those in the field say more information is needed about the drug’s effects over a longer period with more patients — but, they add, the research is a step in the right direction for a better understanding of ketamine.

‘I don’t know that I’d be here’

Ketamine — introduced as an anesthetic in the 1960s and then embraced by ravegoers who called it “Special K” — can balance certain neurotransmitters, rebuild stronger neural connections and alter the mood processes of the brain.

The drug, which is federally approved for short-term sedation and anesthesia, can also be prescribed as an off-label depression treatment. In 2019, the Food and Drug Administration approved esketamine, a nasal spray derived from ketamine and developed by a subsidiary of Johnson & Johnson for people with treatment-resistant depression. And hundreds of ketamine clinics like MindPeace and at-home ketamine therapy services have opened across the country.

However, the unofficial, inconsistent nature of how ketamine is used clinically has limited scientists’ understanding of the drug’s real-world effects on patients who get multiple infusions, as past studies have historically stopped after six infusions.

Oliver said he has found that patients most often begin to see noticeable relief with six treatments, or in about two weeks, depending on the person.

For those at imminent risk of harming themselves, a rapid effect can be lifesaving, especially for cases where traditional treatments such as antidepressants and talk therapy have not worked or are slow to take effect.

Anthony said he had run out of options after he was hospitalized for a seizure caused by the medications he was taking to treat depression. He had lost touch with family members who questioned his diagnosis of depression.

But by at least his fourth ketamine treatment, he no longer relied on his then-fiancée to drive him home after work.

Other medications to treat his depression had made him feel unlike himself, exacerbating symptoms including confusion and disassociation, but he has not had any adverse side effects from ketamine, Anthony said.

“It’s hard to quantify the level of relief,” he paused, “but I don’t know that I’d be here.”

Dissociative effects

The sensation of the ketamine treatment, infused through an IV pump with saline, is unlike anything many patients have experienced before.

Carl Montalbano, a 67-year-old retired MRI technologist, had never used any illicit drugs in his life. He turned to ketamine to treat his medication-resistant depression.

As he leaned back in the large black, reclining chair at the clinic, he ran through the list of what he had tried, including the most commonly prescribed antidepressants, SSRIs (selective serotonin reuptake inhibitors) and talk therapy. All had caused a host of side effects including restlessness, sleepiness and dizziness. Ketamine is “kind of a shotgun approach,” Montalbano said, but it was the most effective in his mind.

“I would not do this if I didn’t have to,” he said. “It’s not fun. It’s therapeutic, and it works.”

Some patients bring music, a blanket or a sleep mask. Montalbano put on his sunglasses, sinking deeper into the chair within minutes of the ketamine and saline entering his bloodstream.

Oliver supervised his patients with the help of two nurses, Melissa Dougher and Brittany Harding, who circle in and out of each room, monitoring heart rates, asking questions and noting any changes on charts.

Montalbano closed his eyes behind his sunglasses.

“I see swirls of color,” he said. “Reds and blues swirling like if you were looking at the cosmos.”

Other patients described distorted hearing, a sense of weightlessness or nausea. Their world shrunk to the clinic room. Within 40 minutes, they were back on their feet.

Montalbano bounded for the door to meet his wife, who drives him home.

Carlos Zarate Jr., the chief of experimental therapeutics and pathophysiology at the National Institute of Mental Health, reviewed the study, saying this real-world research has proved that ketamine has helped people with medication-resistant depression.

But widespread acceptance of the drug will take time, Zarate said, citing a lack of long-term data and the potential for abuse or adverse side effects.

Gerard Sanacora, the director of the Yale Depression Research Program and the Yale New Haven Hospital Interventional Psychiatry Service, said the study, in which he was not involved, raised several concerns about the research: It included only patients who were paying $500 per session out of pocket because insurance does not cover this kind of experimental use of the drug, it does not mention race or ethnicity data, and it provides only limited information about the baseline conditions of the patients. But the data is helpful for researchers, Sanacora said, who are isolated “in ivory towers” and unable to glean how patients at clinics across the country are handling years of ketamine use.

“We still have a little bit more to learn,” said Sanacora, who has treated patients with ketamine in his lab since 2004.

$500 a session

Before he started ketamine treatments, 22-year-old Nicholas was reluctant to try it because his family’s insurance would not cover the twice-a-week sessions that cost about $500 each. A typical ketamine treatment can cost between $400 and $800.

Although ketamine is a relatively cheap drug, Oliver said there are other expenses involved in the treatments, including the staff required to supervise, office rent, medical malpractice insurance and supplies.

But Nicholas, who spoke on the condition that his last name not be used, agreed to try it despite the cost.

He used to call in sick frequently at his job at a 7-Eleven convenience store, a gig that his mother, Liz, had hoped would motivate him to leave his room once in a while. By the appointment for his sixth treatment, he said he no longer felt the urge to avoid work.

Liz brought along her other son with depression, Benjamin, 18, for a consultation during Nicholas’s appointment. Two months after that appointment, Benjamin was cracking more jokes and Nicholas had gone back to college.

Liz said she took a loan out on her life insurance to pay for her sons’ treatments.

“It’s well worth every single penny,” she said, smiling at Nicholas.

‘I come home’

After most patients had left, Harding, one of the nurses who had checked on them, sat in a reclining chair.

After having her son, who is now 4, Harding said she became suicidal, even developing a plan for how she would kill herself. The 31-year-old nurse, who worked at the clinic and the adjoining hospital, at one point, had to leave work early because she was crying hysterically. She said she was taking three medications but could not stop thinking of harming herself.

“I told my husband, ‘Parker is so young, he won’t even know I’m gone,’ ” she recalled, as Dougher prepared her ketamine treatment. “That’s when I realized, ‘I need to do something about this.’ ”

She said she watched as patients would get better at the clinic. She didn’t see anyone’s condition worsen, which encouraged her to ask Oliver if he would take her on as a patient, confiding in him about her struggles.

“He asked why didn’t I come to him sooner,” she said. “I said because I was scared. I’m a nurse, and we’re supposed to be able to handle other people’s problems, not our own.”

She hated the sensation that the psychedelic brought on but noticed an immediate improvement in her mood. She no longer struggled to make herself leave the house for work. She doesn’t think about killing herself. For Harding and her husband, a sheriff’s deputy who has responded to calls involving suicides, ketamine is the answer to a broken mental health-care system. Not only was she saved, she said, but at the clinic, she is part of the important work of helping others.

“I come home every day,” Harding said, “and I’m happy.”

If you or someone you know needs help, you can call or text the National Suicide Prevention Lifeline at 988 or 800-273-TALK (8255). You can also text a crisis counselor by messaging the Crisis Text Line at 741741.