With more than one in five Americans living with mental health conditions, the demand for new treatments has grown. However, much of the focus still remains on talk therapy and medication as the primary options. This is significant because it’s estimated that over 50 percent of people prescribed an antidepressant don’t respond to the first medication they try.
Dr. Rachel Dalthorp is a board-certified psychiatrist and Regional Medical Director with LifeStance Health. She says, “Depression often results in severe impairment that interferes with one’s ability to carry out activities of daily living (ADLs) and is one of the top five leading causes of disability. The number of people living with MDD continues to grow yearly, contributing to a socioeconomic burden of over 200 billion dollars a year, creating a significant and tragic public health crisis, especially considering the 46,000 people a year who die by suicide in the United States.”
Ketamine has gained attention in recent years as a novel treatment. Elvis Rosales, LCSW, Clinical Director of Align Recovery Centers in Northern California, says,” Ketamine has shown promise in managing symptoms of anxiety, PTSD, and certain chronic pain conditions. Its ability to act quickly, often within hours or days, is a significant advantage over traditional antidepressants that can take weeks to become effective.”
Interest in ketamine infusion therapy, in particular, has grown, especially at is has garnered more media attention recently. Dr. Dalthorp explains, “IV Ketamine infusions have demonstrated the ability to rapidly address two challenging to-treat forms of MDD, Treatment-resistant depression (TRD) and Major Depressive Disorder with Suicidal Ideation (MDSI). TRD and MDSI are associated with prolonged patient suffering, significant burden to caregivers, dramatically increased healthcare resource utilization as well as a great cost to patients, families, employers, and society.”
What is ketamine infusion therapy and how does it work?
Ketamine is a type of drug called a dissociative. The exact mechanism through which ketamine impacts depression isn’t well understood, but as early as 1975, ketamine was found to have antidepressant effects. While these effects were also reported by users of street ketamine, because of ketamine’s use as an illegal substance, they were dismissed. It wasn’t until the late 1990s that ketamine’s potential to treat depression was studied in humans.
There are a few different forms. Racemic ketamine is a rapid-acting general anesthetic that was approved by the FDA in 1970 for use as an anesthetic agent in certain kinds of procedures via injection. Initial studies found that a single subanesthetic dose of ketamine infusion improved depressive symptoms of those with MDD and bipolar depression as soon as within one day and that the antidepressant effect lasted three to seven days.
Another form of ketamine called esketamine was found to be even more potent, providing antidepressant properties at a lower dosage. In 2019, Spravato (a form of esketamine delivered intranasally) was approved by the FDA as an adjuvant treatment for treatment-resistant depression in adults. In 2020 it was approved for the treatment of major depressive disorder (MDD) with acute suicidal ideation or behavior in adults.
There are a few ways in which ketamine may be administered for treatment of depression.
Ketamine infusion: thought to be the form the body is best able to absorb, in ketamine infusion therapy, ketamine is delivered intravenously. This takes place in a hospital or clinic setting and takes about 40 minutes. A ketamine infusion protocol typically includes six treatments over the course of about three weeks but can vary depending on what is determined to be best for the individual patient.
Intramuscular injection: Performed in a hospital, clinic, or office setting, a single dose of ketamine is administered into a larger muscle, typically in the arm or thigh. This also lasts for about 40 minutes.
Intranasal spray: Spravato is currently the only FDA-approved ketamine treatment for depression (which means that the other forms may be used off-label) so insurance may cover some of the cost. This intranasal spray is administered in an office setting, after which the patient is monitored for side effects for two hours. It’s also possible to have a ketamine nose spray mixed to your doctor’s specifications at a compounding pharmacy.
Lozenges: Taken orally, lozenges are used for low-dose ketamine treatment. They may be taken at home or in a clinic setting. For some patients, they may be the primary treatment, or they may be used for maintenance in between infusion, intramuscular, or intranasal treatment.
Potential benefits of ketamine
Licensed psychotherapist Hilary Stokes PhD, LSCW, says, “There are numerous potential mental health benefits to ketamine infusion therapy. These can primarily be found in the areas of depression, anxiety, developmental trauma, OCD and PTSD. Over time and with more research, the mental treatment conditions benefiting from ketamine will continue to expand. I have worked with many clients who have undergone ketamine therapy and have had positive experiences. Clients have had breakthroughs in areas they had felt previously blocked or emotionally stuck. They often report feeling as though they accomplished in a few ketamine sessions what would have taken years of therapy.”
She explains that this is related to ketamine’s impact on specific areas of the brain such as the default mode network (DMN), brain derived neurotrophic factor (BDNF) and the neurotransmitter glutamate. “As the DMN is quieted during the treatment, an individual is given a break from this part of the brain that watches over, keeping one on guard and rigidly holding to old patterns. It can be like hitting a brain reset button. This allows for someone to see their life, events or issues from a different perspective where they take in a bigger picture view from the present moment or have a breakthrough on an area they have felt stuck. Combined with changes in DMN, BDNF and glutamate have an impact on neural plasticity or the ability to create new brain pathways. This results in new ways of thinking, feeling and acting.”
Theodora Blanchfield, AMFT, works with clients on ketamine-assisted therapy and psychedelic integration. She says, “The reason ketamine has been so lauded is because it does have so many mental health benefits, and the biggest advantage it has over older treatments like SSRIs is that people see its benefits immediately.” She adds that this is particularly important for extremely depressed or suicidal patients for whom waiting a few weeks for a medication to kick in isn’t an option. “Ketamine treatment has been shown to help treatment-resistant depression, anxiety disorders, PTSD and substance use disorders.”
Risks of ketamine
There are some risks to be aware of when considering ketamine treatment, and patients using ketamine should be closely monitored.
While ketamine is considered a very safe medicine, explains Blanchfield, “it is still a medicine that produces non-ordinary states of consciousness and is something to be taken seriously. Physical risks include an elevated heart rate, nausea and dizziness. Rare psychological risks include hallucinogen persisting perception disorder or psychosis, which is why it is important for patients to be screened thoroughly in advance. Difficult feelings or memories may come up for someone while receiving a ketamine infusion. While these can feel distressing at the time, they may ultimately be healing as long as someone is also receiving therapy to process and integrate these experiences.”
Dr. Stokes says, “Finding an experienced provider who is approved to administer ketamine in a professional setting is essential to safely receive ketamine therapy. Ketamine is dosed based on body weight and often administration will be titrated from session to session to make sure a client is safely adjusting to the treatment.”
She adds. “Ketamine can be an addictive substance and should be administered under professional guidance. The overall set and setting is a vital component to successful treatment. If this is not in place there can be risks to not only successful treatment but also to health and wellbeing.”
This is why it’s absolutely vital, she explains, to work with providers who have the proper training and expertise to safely administer the therapy as well as provide appropriate therapeutic guidance after each ketamine session. “The latter may be one of the most important yet often overlooked elements of treatment,” Dr. Stokes explains. “Given the powerful benefit of neural plasticity that ketamine provides, integration is a significant part of treatment. There is otherwise the risk of not sustaining the insights and breakthroughs or not establishing healthy lifestyle habits that coincide with positive mental health.”
Ketamine as part of an integrated mental healthcare model
Ketamine is also being used as a complement to other mental health services.
Dr. Allie Sharma, a Cornell-trained board-certified Adult Psychiatrist, is the chief medical officer and co-founder of Being Health, a new mental health practice that takes an integrated approach to mental health care. The practice’s first location recently opened in New York City’s Financial District, with plans to open more locations. “This is a modern mental health practice. We take what is tried and true and pair it with the novel. We’ve developed what we’re calling an integrated care model—all services under one roof.” The company offers treatment for anxiety, stress, depression, and trauma, with individualized, evidence-based practice and provider collaboration being key facets of the patient experience.
“We are all so complex,” explains Dr. Sharma. “As a psychiatrist, the way we evaluate a person is comprehensive.” A provider looks at the patient’s physical and mental health as well as their environment. “We really assess the risk factors and which things may be contributing to their issues or protecting them. We can think about therapy, medication, and referring to other services.”
Being Health currently offers psychiatry, psychotherapy, functional medicine, wellness (including acupuncture and nutrition) as well as novel practices, including ketamine infusion therapy. The ketamine therapy program, Dr. Sharma explains, was developed as a collaboration between psychiatry and anesthesiology over the course of a year-and-a-half to help address treatment resistant depression, treatment resistant anxiety where it’s comorbid with TRD and Post-Traumatic Stress Disorder. “Safety is first and everything is well thought out. We don’t want people who might benefit from ketamine infusion therapy to be afraid of it.”
“All patients go through a thorough psychiatric and medical evaluation which screens for [physical] and mental health conditions that may increase risk for complications.” This evaluation may include coordination with the patient’s primary care providers or other specialists involved in their care, explains Dr. Sharma, “and lab work and in some cases urine toxicology may be ordered based on our clinical protocols. Patients are enrolled into Being Health’s ketamine program according to a set of criteria that accounts for medical, psychiatric and substance dependence risk.”
At Being Health, ketamine-assisted psychotherapy (KAP) is utilized alongside ketamine treatments in order to maximize and prolong the benefits, so all clients receiving ketamine treatments have at least one preparation therapy session and are offered integration therapy sessions alongside their ketamine treatments.
Dr. Sharma explains that “ketamine infusion therapy has the most robust scientific evidence supporting its use in treating mental health conditions.” It also provides certain other advantages, she adds, “including being able to slow or stop an infusion during treatment if needed, and its high bioavailability, meaning that we know very accurately the amount of the medicine that enters your bloodstream.”
During each ketamine infusion, patients are medically monitored by a Certified Registered Nurse Anesthetist (CRNA) and a member of the Being Health team is present to provide assistance. “Once the therapy concludes, patients will be able to cool down in a controlled environment while still being medically monitored,” adds Dr. Sharma. “Following an infusion, and in accordance with a personalized care plan, the patient will meet with the KAP therapist for integration sessions and clinical monitoring.”
Talking to your doctor about ketamine
Considering ketamine treatment? Blanchfield says not to be shy with asking questions. “ Mindset and the physical setting are important in psychedelic work, and patients should ask providers whatever they need in order to feel comfortable to embark on a ketamine journey. Ketamine work can be incredibly healing and profound, but it is a major undertaking not to be taken lightly.”
Rosales adds, “This discussion can help patients make informed decisions and set realistic expectations for the outcome of their treatment.”
It’s especially important to make sure the provider has the proper training and credentials to be administering the treatment. Asking your healthcare provider the right questions can help you have the best experience. Here are a few things experts recommend asking:
- What are the expected benefits and potential side effects?
- What is the treatment setting?
- How many sessions might be needed?
- How does ketamine interact with other medications or health conditions?
- What is the provider’s experience and track record in administering ketamine therapy?
- How are patients monitored for side effects?
- How are side effects managed if they do occur?
- What is the plan for post-treatment care?
- What is the integration process like?
Financial considerations can also be an important factor. Dr. Dalthorpe says, “Patients should also inquire about cost and insurance coverage. In addition to evidence regarding the efficacy and safety of IV racemic ketamine, there is a strong argument that the cost-benefit associated with the use of a generic drug, albeit off-label, must be considered given the current unmet need for TRD treatment in the population and limited health care resources.”
Exploring ketamine infusion therapy
For those who decide to explore ketamine therapy, it can be extremely overwhelming to look for professionals in your area—and how can you tell which ones are trustworthy? While asking your doctor or psychiatrist for a recommendation may be a place to start if a ketamine-specific resource to explore is the American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP) directory. Members are required to agree to a strict set of standards and ethics so this can help you find a credible professional with expertise in this area. Don’t be afraid to speak to a few different providers to see who feels like the best fit for you.
And if you are currently experiencing suicidal thoughts, contact the National Suicide Preventine Lifeline at 988 to get support from a trained counselor. You can also visit the National Institute of Mental Health for other kinds of mental health resources.
