Editor’s Note: In “Hey, Health Coach,” Sarah Hays Coomer answers reader questions about the intersection of health and overall well-being. Have a question? Send her a message (and don’t forget to use a sleuthy pseudonym!).
Hey, Health Coach,
I’m seeing articles about ketamine treatment for depression all over the place. I’ve been low-level depressed for years. I’ve tried a few antidepressants, but they didn’t do much and messed up my sex drive. Ketamine seems like an extreme approach, but I’ve read some pretty amazing success stories. I’m nervous about it but wonder if it would live up to the hype. Does ketamine actually work for treating depression?
— Keta-Curious
Dear Keta-Curious,
I’m sorry to hear you’ve been struggling with depression and traditional treatments haven’t worked like you hoped they would.
If you have a trusted psychologist or psychiatrist, they may be a great resource to help you explore your options. I’m not a therapist and can’t speak to your unique situation, but I can help sort through the evidence about ketamine for depression and clarify what it might be like to receive treatment.
As you mentioned, there’s a great deal of hype surrounding this question—with good reason. A lot of people are struggling with depression.
According to the Centers for Disease Control and Prevention (CDC), 22% of the U.S. population has symptoms of depression[1]. Meanwhile, a 2021 study in the Journal of Clinical Psychiatry reports that 2.8 million people in the U.S. experience treatment-resistant depression at an annual cost of nearly $44 billion[2]. That’s a lot of heartache, expense and time lost to this mental health condition.
As you know too well, traditional medications don’t work for everyone, and they can cause a long list of side effects. If alternatives exist, they certainly deserve a second look, but does ketamine live up to the hype? If so, how does it work, and what is the safest, most effective way to receive treatment?
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What Is Ketamine?
Ketamine is a dissociative anesthetic approved by the Food and Drug Administration (FDA) for use in both humans and animals. This generic form of the drug (a compound of both R- and S-ketamine molecules) isn’t approved for the treatment of any psychiatric disease, but it’s frequently prescribed off-label in clinics and via at-home delivery for depression, anxiety and other mental health concerns.
Prescribing medications off-label is common practice in the U.S. Other examples include Mounjaro, a diabetes drug being used for weight loss, and lorazepam, an anxiety drug that’s also prescribed for nausea in people with cancer.
However, Spravato (esketamine) is a patented nasal spray that contains only the S-ketamine molecule. Spravato has been approved by the FDA for adults with treatment-resistant depression since 2019. Administering esketamine requires a strict protocol called a Risk Evaluation and Mitigation Strategy (REMS), which includes delivering treatment in a health care setting and monitoring patients for at least two hours after they receive the drug.
Does Ketamine Help With Depression?
A comprehensive systematic review of 83 studies in the British Journal of Psychiatry reports that evidence shows “robust, rapid and transient antidepressant and anti-suicidal effects of ketamine.” Translation: Ketamine works quickly and effectively, but the antidepressant benefits from a single session can be short lived[3].
Meanwhile, a 2022 meta-analysis in the Journal of Psychiatric Research confirms substantial clinical effectiveness of ketamine for treatment-resistant depression. The authors write that “even the most treatment-resistant patients may benefit from ketamine” and note that repeated treatments maintain their potency, continuing to be helpful for people who receive prescribed doses over extended periods of time[4].
How Does Ketamine Work?
Research shows ketamine works on the brain in three fundamental ways, according to Reid Robison, M.D., a psychiatrist and chief medical officer at psychedelic therapy company Numinus.
First, ketamine helps restore glutamate signaling. Glutamate is a prevalent neurotransmitter implicated in depression but not affected by traditional antidepressants (selective serotonin reuptake inhibitors, or SSRIs).
Second, it helps quiet a part of the brain called the lateral habenula, which Dr. Robison calls the “anti-reward center” of the brain, noting that it gets stuck in overdrive when we’re stressed and that ketamine can “act as a reset button.”
Third, ketamine can support neuroplasticity, which makes growing new neurons and forming new connections easier and supports the reversal of depression.
Dr. Robison cautions that while ketamine is fast acting, its antidepressant effects are often temporary. Still, its short-term relief can provide an opportunity for people to see what’s possible when depressive thoughts are alleviated and to work more effectively with other interventions to improve long-term well-being, including talk therapy.
He adds that it’s important to distinguish between receiving ketamine by itself and ketamine treatment in conjunction with mental health services, such as therapy or additional psychiatric treatments.
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Potential Side Effects of Ketamine
A 2020 comprehensive review of the side effects of ketamine for depression in the Journal of Affective Disorders reports that the most common side effects during ketamine treatment tend to be drowsiness, dizziness, poor coordination, blurred vision and feeling “strange” or “unreal.” Some people also experienced headaches, dissociation, anxiety and elevated blood pressure. The authors report that all side effects resolve quickly after the treatment[5].
One additional note of caution: Taking ketamine in combination with levothyroxine (Synthroid) for hypothyroidism can increase blood pressure and heart rate. Check with your health care provider or the ketamine clinic health care team if you take this medication.
Are At-Home Ketamine Delivery Services Legal and Safe?
During the COVID-19 pandemic, the federal government declared a public health emergency, which loosened the rules around when and how health care providers could prescribe controlled substances via telehealth. This shift fostered a booming industry of companies that send ketamine directly to people through the mail.
As with clinics, some telehealth companies have thorough screening processes and support systems. Others send the drugs after a quick questionnaire or brief video consultation, advise having a “sitter” at home when taking ketamine and leave people to their own devices.
As the public health emergency ended in May 2023, it was expected that health care providers would be required to meet with their patients in person (or have a third-party physician meet with them) before prescribing controlled substances. However, after an enthusiastic period of public comment, the Drug Enforcement Administration (DEA) decided to extend the current rules temporarily while considering what to do next.
For now, health care providers may continue to prescribe ketamine via telehealth and send the drugs by mail. This practice allows for greater accessibility, especially for people in rural areas or who are unable to travel, but many question the safety and efficacy of ketamine without accompanying therapy.
Payton Nyquvest, CEO of Numinus, believes sending ketamine to unsupported patients struggling with mental health is akin to “mailing a scalpel to somebody’s house and saying, ‘Go ahead and do open heart surgery on yourself.’”
“It’s scary,” he says. “Do some people benefit? I’m sure they do. [But] do I think the risks outweigh the potential benefits? For sure.”
What Is a Typical In-Person Ketamine Treatment Like?
Dr. Robison emphasizes that ketamine treatment plans are unique to each patient based on their individual needs. However, a single course of in-person ketamine treatment would likely include the following:
Preparation
The patient meets with a trained provider to understand the medication, learn what to expect from the experience and formulate intentions for the course of treatment.
Treatment Day
The patient receives their dose of ketamine in a safe, comfortable environment. In psychedelic therapy, this process is known as “set and setting” and often includes lying down with a blanket, eye mask and headphones playing curated music. Therapists stay in the room and interact as needed, but Dr. Robison says the experience is often inward facing with the opportunity to process discoveries after the medicine wears off. The ketamine lasts approximately one hour, but patients can expect to be in the clinic for two to three hours to allow time to debrief before going home.
Integration
Dr. Robison recommends several integration sessions after the treatment day, highlighting that a mental health team can be especially useful in this phase to help people process and utilize the insights they gained while on ketamine.
“Things come up,” he says. “Sometimes people feel a little worse before they feel better on the healing journey, so it’s important for them to be supported in the process.”
Additional Support
Dosing sessions can be provided once or in a series. The number of treatments one might need is unique to their individual situation and should be determined by their physician. Furthermore, some ketamine clinics offer intravenous (IV) infusions, nasal sprays or lozenges as part of a larger care plan. Others do so in isolation without any preparation beforehand or integration afterward.
Dr. Robison says ketamine can also be administered in much lower doses during traditional talk therapy sessions to facilitate openness and create a “mind-loosening” effect.
In addition to therapy, health coaches work with some clinics to help people undergoing ketamine therapy implement lifestyle changes that contribute to mental and physical well-being in the weeks and months following ketamine treatment.
Does Insurance Cover Ketamine for Depression?
Because Spravato has been approved by the FDA for treatment-resistant depression, it’s usually covered by health insurance. The data on its safety and efficacy is increasingly robust, so insurance companies are slowly coming around to approving ketamine for depression, especially in cases where two or more traditional antidepressants have failed, says Dr. Robinson.
Some insurance plans require the patient to pay out of pocket. In such cases, prescribing generic ketamine off-label is considerably less expensive than prescribing the patented Spravato, adds Dr. Robinson.
In 2022 the FDA issued a statement clarifying that it cannot verify the safety of compounded ketamine nasal sprays (containing both R- and S-molecules), urging caution for prescribers.
Regarding IV ketamine specifically, more and more insurance companies are either partially covering or reimbursing for this treatment. However, most patients are still responsible for paying for the treatment themselves.
What to Look for in a Ketamine Clinic
Dr. Robison encourages people seeking help with depression to make sure the clinic they’re considering employs licensed mental health physicians on its care team and to look for clinics offering “ketamine therapy” or “ketamine assisted psychotherapy (KAP)” rather than standalone ketamine infusions. The best option is a clinic led and run by mental health professionals as opposed to a clinic run by non mental health professionals, such as anesthesiologists or emergency room physicians. Psychiatrists are the only physicians with specialized training in the diagnosis and treatment of depression and anxiety and are best equipped to assess whether someone is a good candidate for the treatment. In an increasing number of jurisdictions, ketamine clinics are being required to hire mental health professionals to assess patients.
Under the right circumstances, ketamine shows enormous promise as a treatment for depression, but no single treatment is right for everyone. Check with your health care provider to determine whether it’s a good option for you, and if you do decide to proceed with ketamine therapy, make sure the clinic you choose is taking care of your mental health, not just dispensing drugs.
“Hey, Health Coach” is for informational purposes only and should not substitute for professional psychological or medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health provider with any questions about your personal situation, health or medical condition.
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