A RECOVERY STORY: After Every Available Option Was Exhausted, Ketamine Has Enabled Her Life to Resume

Making a peanut butter-and-jelly sandwich is something people do almost mindlessly, or so you might say. But it is a task that involves a number of very real cognitive challenges: you have to remember where the peanut butter, jelly, and bread are. You then have to remember the steps involved, find the butter knife, and know what you’re supposed to do with it. Not least, there’s the energy-demanding task of eating it.

As 29-year-old Ashley Clayton stood in her kitchen, she found herself at a loss as to how to do any of those things.

“I never appreciated it until I couldn’t do it,” she recalls—what a complex series of brain functions are required to be able to hold all those things in your mind at once. And I couldn’t do it.”

Ashley had been undergoing intense electroconvulsive therapy (ECT) and it had impaired her cognition. This, compounded by her underlying condition, chronic major depression, made even the simplest cognitive tasks a challenge.

ECT, in which an electrical current is run through the brain of an anesthetized patient in order to induce a therapeutic seizure, is considered to be one of the best available treatments for treatment-resistant depression. And yet, after 17 sessions, three of which were of the more aggressive bi-frontal type in which both sides of the brain are stimulated, Ashley’s depression remained relentless.

I’m failing the best treatment they have,” she thought, spiraling into despair. She felt like it was only a matter of time before her illness inevitably would kill her.

This wasn’t the first time that Ashley had contemplated suicide.

A childhood marred with serious trauma had triggered her depression and PTSD when she was in middle school. On the outside she looked like a thriving teenager. She loved school, especially art class. She walked around with a paintbrush tucked into her messy ponytail. She got straight ‘A’s. Yet, her feelings of guilt, shame, and loneliness grew stronger, until she tried to take her own life at age 14 and ended up in the psychiatric unit of a local hospital. Over the next 4 years, Ashley was hospitalized twice more, once after a near-death suicide attempt during senior year.

She made it through and became the first person in her family to go away to college. She came home that first semester after she began hurting herself again. However, Ashley had always loved school and wanted badly to go back. She worked hard at recovery, attending intensive outpatient clinical therapy and learning skills to manage her depression and PTSD.

She returned to college that spring, continuing to work through her trauma and developing coping skills in therapy. By the time junior year rolled around, she, for the first time in her life, felt well. In 2009, she graduated with honors and moved to New England from her home in Kentucky to earn a master’s degree in community psychology.

At that time, in her early twenties, Ashley was successfully managing her symptoms with medication and psychotherapy. She fell in love with a man she would marry. She did her internship at a lab at Yale University. Feeling more rooted and settled than she had ever been, she graduated at the top of her class and was offered a full-time position as a researcher at Yale.

New Depths

However, in 2012, stressful life events brought up past trauma, and set off a prolonged depressive episode, which only became worse with time. In 2014, the year she got married, Ashley’s depressive symptoms came back full force. As she started a new position at the university, her mental health continued to decline.

She experimented with a dozen different medications—nearly every class of anti-depressants. She tried several different kinds of talk therapies, including dialectical behavioral therapy and cognitive behavioral therapy.

Nothing worked. And the loneliness and extreme fatigue consumed her.

“For the first time in my life I had a profound inability to experience any pleasure,” she remembers.

As 2016 began, so did Ashley’s severe functional impairments. She found it difficult to read, concentrate, and remember. Reading an academic article for work demanded more energy than she could muster. On the recommendation of her psychiatrist, she took a partial medical leave. Her inability to perform her cognitively demanding job was particularly devastating, since she derived so much meaning and fulfillment from work.

Desperate for solutions, she reached out to a friend and colleague involved in research on ketamine, an anesthetic that has been used experimentally for two decades to generate rapid antidepressant effects. Ketamine has been handled carefully and its progress has been slow owing to its side effects which include addiction and dissociation, a disconcerting feeling of being detached or outside of one’s own body.

Ashley was put in touch with Gerard Sanacora, M.D., Ph.D., a leading authority on ketamine and mood disorders. Dr. Sanacora is a professor at Yale and member of the Scientific Council, who, over the course of his career, has received four of the Foundation’s grants—two as a Young Investigator and one each as an Independent and Distinguished Investigator.

After learning about Ashley’s situation, Dr. Sanacora identified a double-blind Phase II clinical trial of ketamine in patients like her who were seriously ill and had not been helped by multiple prior antidepressant treatments. Phase II trials seek to determine the most effective dose, and in this trial, only a single “rescue” dose of ketamine was administered to each participant.

A Stunning Reversal

About a week later, Ashley found herself in a hospital bed in Yale’s hospital research unit, receiving an intravenous infusion. At the time she didn’t know if she had received ketamine or a placebo. (Later it was confirmed to have been ketamine, administered at one of the four tested dosages). After getting the treatment, nursing nausea and a bad headache, she went home and slept it off.

When she woke the next morning, Ashley felt 50 pounds lighter. She could breathe. She wanted to go for a run. So, she did. Although she often ran to try to manage her depressive symptoms, she couldn’t recall ever having wanted to go for a run.

“I can’t even explain to you how dramatically different I felt when I woke up....It was a miracle,” she says. She could feel positive feelings, which had eluded her for the last two years.

“I looked at my husband and I felt love,” she remembers. “Not being able to experience that is incredibly painful.”

Approximately 2 weeks later, Ashley woke up to full-blown depression symptoms. It wasn’t a gradual remission, but a precipitous fall off a cliff. For 2 weeks, then, she had experienced what her life could be. But now the grief of having that suddenly torn away accompanied the return of her depression.

The single dose of ketamine had worked, but only temporarily, as it does in most other patients. Could she arrange to have more treatments? Her university-sponsored insurance wouldn’t cover a drug that the FDA has yet to approve for depression (FDA approval is closely tied to insurance coverage). At around $1,000 a dose, ketamine, which remains “experimental,” is a drug that only a few can access.

However, the Yale-affiliated hospital did have an Interventional Psychiatry Service which offered ketamine as a clinical treatment to individuals with severe, treatment-resistant depression. Her doctors said they would try to get Ashley into the program. In the meantime, her doctors made slight changes in her medication regimen, but very few treatment options remained.

At this point, Ashley felt certain of her suicide. It physically hurt to breathe.

“The amount of physical pain just from trying to function was just overwhelming,” she recalls.

With suicide in mind and ketamine still out of reach, Ashley reached out to another colleague, who suggested ECT, an option she had not yet entertained, fearing its cognitive side effects, including memory loss. ECT is much safer and more effective than it was decades ago, but different patients respond differently to it. Some don’t complain of cognitive effects such as memory loss. Others do.

Feeling at the end of her options, Ashley admitted herself to a psychiatric hospital and began a series of acute ECT treatments. She was discharged after a month and continued her treatments as an outpatient. It was after the 17th session that Ashley found herself in her kitchen, unable to make that peanut butter-and-jelly sandwich. “It was like I didn’t have a working memory,” she says.

She still had no word on the status of her ketamine request. Her depression persevered, tangled with the side effects of the ECT.

“The most important thing to me was just my ability to think. And I was losing it,” she says.

Life-Saving News

During what would be her final ECT session, Ashley reached out to the head of the ECT program about her earlier request to receive ketamine again. He promised to look into it. Two days later he gave her what turned out to be life-saving news: “It seems like ketamine is the best treatment for you. So, let’s do that.” And just like that, after months of waiting, she had been approved. That very day, a few days before Christmas of 2016, she received a ketamine infusion.

After four weekly treatments, Ashley began to feel almost like she had after that first infusion at the beginning of the year. She and her doctors faced what is a common barrier to continued ketamine therapy—finding a way to pay for the treatment. It appeared that her depression could not be managed without ketamine, and after a few months of receiving care on a treatment-by-treatment basis, her doctors were able to convince the hospital administrators to provide her with free care over the long term.

Since then, she has received ketamine every 2 to 3 weeks, depending on her symptoms. She also continues to be on two other medications. She is in constant touch with her doctors.

“Ketamine not only saved my life, but has restored me to the joys, and pains, of full living. I feel, for the first time in my life, like there is air to breathe,” she says.

Ashley’s well-being depends on continued access to an experimental drug that her insurance will not cover, and whose safety and effectiveness with long-term use still has not been clinically demonstrated. Now 31, Ashley Clayton is likely among the people with treatment-resistant depression who have been treated with ketamine for the longest continuous period. This makes her case particularly valuable to researchers who can monitor her progress and any side-effects she might experience.

As a mental health researcher herself, Ashley recognizes this. “It’s an amazing drug that needs more research, funding and insurance reimbursement,” she says, “but also it needs to be done really thoughtfully. Patients need to be very followed very closely.”

For now she is happy to know that she and her doctors have at last found something that can keep her depression, and thoughts of ending her life, at bay.

— Written By Fatima Bhojani

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