Ketamine’s Brain-Changing Effects


ARLINGTON BIBLICAL scholar D.T. noticed a surprising after-effect of the light anesthetic she received for orthopedic surgery: the depression she’d been fighting for years with an array of medications, which had worsened recently, started to lift.

The anesthetic: ketamine, used in orthopedic surgery because it can reduce post-operative pain, is in the class of drugs known as dissociative anesthetics that includes PCP and nitrous oxide.

Because most adults don’t like the feelings of detachment and hallucinations ketamine can cause, it is most commonly given in pediatric surgery. Kids seem not to notice what D.T. calls the “trippy” effects.

Starting about 20 years ago, low-dose (subanesthetic) ketamine given to patients for chronic pain appeared to allay their depression.  Chronic pain and depression are often “inextricably intertwined,” with treatments including antidepressants and electroconvulsive therapy (ECT) effective against both.

But it turned out that patients suffering treatment-resistant depression without other physical or psychiatric illness also benefited from ketamine.

“Night and day,” was how D.T. described the difference.  “Post-op I felt like a normal person for the first time in years.” Compared to SSRI medications (e.g., Zoloft and Prozac) that take weeks to work, she said, “ketamine, one dose, and bam, [I felt] totally different.”

“The most important breakthrough in antidepressant treatment in decades,” is how Thomas Insel, past director of the National Institute of Mental Health, referred to ketamine.

In the past few years, clinics offering ketamine infusions for mood disorders have multiplied around the country.  Actify Neurotherapies, which oversees ten clinics including the Potomac location that D.T. uses, received 28,000 inquiries in the first nine months of 2018.

And this March, the FDA approved the first ketamine-based drug to treat depression, although its reception was tepid. Because esketamine is a nasal spray, some worry about uncertainty of the dose —like D.T., who points out that worries could affect attitude, which plays an important role in the ketamine experience.

Ketamine doses for “treatment-resistant depression”—defined as major depression that hasn’t responded to two or more medications—range from 40 to 80 milligrams per kilogram of body weight. That’s about one-tenth the amount used recreationally in the drug known as “special K.”  (Higher ketamine doses are used for anesthesia as well as for veterinary euthanasia.)

Ketamine’s mood-enhancing effects emerge in about four hours—providing a quick “window of relief,” especially for patients who might be contemplating suicide.  Rapid reduction of suicidal thoughts can allow time for sufferers to get more in-depth treatment.  That “window” can also demonstrate to those with intractable mood disorders that something exists to help them.

Unusually for a mood-disorder drug, ketamine appears to help with both depression and anxiety—two diagnoses traditionally viewed as distinct but increasingly seen for their overlapping symptoms, such as problems with sleep and fatigue, irritability and difficulty concentrating.

“Some people react with anxiety to life stressors—and some people, in addition, go beyond that to become depressed,” said David Barlow, director of the Center for Anxiety and Related Disorders at Boston University.

Anywhere from 50 to 70% of those diagnosed with depression also suffer anxiety.  When co-existing, these conditions can become more chronic, impair functioning at work and in relationships and “substantially raise suicide risk.”

The effects of ketamine can be different for each diagnosis: for depression lasting one to two weeks and, for anxiety, more than two months—although individual reactions can vary.

Ketamine may work by increasing the neurotransmitter glutamate, which appears to help neurons communicate with each other along new pathways and facilitate communication among specific areas in the brain—known as neuro-connectivity.

“There is no ‘I,’ time disappears, you are released from negative inner emotions like anger, and you can surrender,” Gabor Maté, a Canadian physician specializing in childhood trauma and psychedelic-based therapy, told a recent Psychotherapy Networker conference in D.C.

“You feel less separate from the rest of the universe, part of the plasma,” D.T. said.”  “You feel more alive.”

Visually, ketamine often creates bright colors and images—called “visions” (rather than hallucinations that can be hard to distinguish from reality). D.T. compared her experience to a dream: “You know that you can open your eyes any time and see what’s really there.”

With her eyes closed, she has been “out west; in a baroque-styled room; and in a video chasing something.”  But for her, the strongest sensory effects were auditory: “I was inside the piano.”  For people embarking on ketamine therapy, she “strongly suggests they bring music that makes them feel happy.”

To allow for slow increases in dose as needed, the Actify protocol begins with a series of five infusions given over a three-week period, D.T. explained. Before and after each infusion, patients speak with a doctor; and afterwards they fill out questionnaires on depression and anxiety. During the hour or so of each infusion, medical professionals check bloodpressure and general well-being. The entire appointment lasts about three hours.

After taking two antidepressants “for years,” on the advice of her psychiatrist D.T. stopped both within months after starting ketamine—a big financial savings to her, she noted.  Each ketamine infusion at Actify costs just under $500 (not covered by insurance).

After more than 12 infusions altogether over little more than a year, D.T. has had no physical side effects, which is true for most who have tried the therapy.  If there’s a downside, she said, it’s heightened sensory sensitivity so that, for example, “the mall is too much.” Side effects, which occur more often among those who regularly take recreational doses, can include bladder issues such as cystitis.

On the other hand, patients can develop tolerance to therapeutic ketamine, requiring ever-higher doses—making the drug potentially addictive. But D.T. has been requesting lower doses, saying, “I want to see how low I can go and still feel better afterwards.”

An investigation by STAT News found wide-ranging inconsistencies among the clinics—with a number straying from recommendations issued last year by the American Psychiatric Association.  While some like Actify have psychiatrists on staff to do intake checks at each infusion, many had no mental-health professionals.

The clinics surveyed charged anywhere from $350 to close to $1,000/infusion. And many overhyped the treatment, which can help 70 to 85% of patients, but effects vary among individuals.

When it works, ketamine provides another step before the final, more drastic option of ECT.  While ECT has been modified over the years and is considered very effective against depression, it can have serious side effects, notably memory loss.

And compared to SSRI medication, D.T. points out, “ketamine’s success would be much better even if it helped only 50%.”

—Mary Carpenter

Well-Being Editor Mary Carpenter reports on news you can use right here every Tuesday.

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