Is Ketamine-Assisted Psychotherapy the Cure for Tough to Treat Depression?
- By Rebekah Harding
- and Lara McGlashan
- Fact-checked by Jennifer Chesak
- Fact-checked by Katherine Wessling
- November 7, 2023
30-Second Takeaway
- Ketamine may promote structural changes to your brain pathways, which could help treat treatment-resistant depression, anxiety, and Post-Traumatic Stress Disorder (PTSD).
- Ketamine-assisted psychotherapy involves a rigorous screening process before you can get approved.
- While many people feel relief after the first session, they may need several sessions before noticing lasting results.
Twenty years ago, you’d most likely stumble upon ketamine—a popular hallucinogenic drug—at a bustling EDM rave, Burning Man, or a woo-woo wellness retreat. But now, a growing number of clinicians are offering ketamine-assisted psychotherapy (KAP) to care for people with treatment resistant depression or PTSD.
“For many patients who live with mental health challenges, existing pharmaceutical treatments (like SSRIs) don’t always work,” says Jonathan Sabbagh, co-founder and CEO of Journey Clinical, where they regularly use ketamine to treat patients with PTSD and treatment-resistant depression. “In fact, up to 30 percent of patients diagnosed with major depression are resistant to conventional treatments. In recent years, various studies have questioned whether SSRIs provide long-term improvements in quality of life.”
Ketamine and the Brain
“As research into the effectiveness of KAP increases, more and more people are becoming aware of the benefits of psychedelics on the brain to treat mental health conditions,” says Dr. Pamela Walters, medical director and consultant psychiatrist at Eulas Psychedelic Clinic in Scotland.
For example: A recent study published in The New England Journal of Medicine found that 55 percent of patients who received ketamine treatments experienced sustained improvement in depressive symptoms—without major side effects (1).
The possible connection: Ketamine blocks the activity of N-methyl-D-aspartate (NMDA), a glutamate receptor involved in pain perception, mood regulation, and cognitive function (2).
Research shows ketamine may also regulate glutamate levels. Low levels of glutamate are commonly found in people with depression (3). Ketamine may also stimulate mTOR, an enzyme that promotes activity in the prefrontal cortex and hippocampus—two areas of the brain responsible for emotional regulation (4).
Ketamine may also promote structural changes to your brain pathways. For this reason, ketamine has grabbed the attention of neuroscientists and psychologists for its potential mental health benefits.
KAP isn’t FDA approved nor is the science a slam-dunk yet. But Walters says there are currently several large studies researching the effectiveness of KAP for treatment-resistant depression, OCD, trauma, anxiety, and addictions.
ABOUT THE EXPERTS
Dr. Pamela Walters is a consultant psychiatrist with expertise in general adult, addiction and forensic psychiatry. She was Clinical Director and Responsible Officer at The Forward Trust from 2017-2022 and the National Advisor for psychiatric standards for the Parliamentary and Health Services ombudsman. Dr Walters is involved in clinical trials in the UK with psychedelics medicine in the mental health field.
What is Ketamine-Assisted Psychotherapy?
If you have depression or PTSD, the standard protocol is to undergo talk therapy, often in conjunction with antidepressants. But for severe cases, this approach can fall short.
Traditional therapies can work for some people’s mental health problems, but for those with treatment-resistant mental health issues, ketamine can make therapy sessions more effective, Walters explains.
According to Sabbagh, working with a therapist in combination with ketamine treatments can create the conditions needed to go “deeper,” which can lead to “…the possibility of more frequent breakthroughs and longer-term improvement in clinical outcomes.”
The research is aligned: According to a review of studies published in 2022 in the Journal of Pain Research, the ketamine-psychotherapy combo was found to potentially be more effective than either treatment on its own (5). Together, it’s thought the duo could increase treatment engagement between the patient and therapist, help build trust, and lower feelings of defensiveness.
Why are docs turning to the psychedelic to enhance therapy?
Unlike antidepressants, which are thought to work by increasing neurotransmitters like serotonin (6), ketamine induces neuroplasticity, or your brain’s ability to change and adapt to new experiences, explains Walters. Increasing neural connections helps to embed therapy treatments in patients.
Research shows that this increased neuroplasticity can help rewire the neural pathways responsible for long-held beliefs, PTSD triggers, intrusive thoughts, and compulsions when paired with talk therapy (7, 8).
What Happens During a Ketamine-Assisted Psychotherapy Session?
Before you can even get started, there’s a rigorous screening process, says Walters. To be approved for ketamine-assisted therapy, a doctor will need evidence that two different types of antidepressants or therapy haven’t worked.
Once approved, you’d undergo counseling to learn about potential positive or negative reactions (like intense breakthroughs or unlocking traumatic memories) to treatment, Walters explains. “Although both experiences can occur, they are both therapeutic and beneficial to the treatment process.”
Ketamine is administered through an IV (intravenous ketamine infusion) or under-the-tongue lozenge. You can also take a form of ketamine called esketamine (under the brand name Spravato) via a nasal spray.
Typically, you’d have multiple sessions in a week over several months.
While many brick-and-mortar ketamine clinics require on-site sessions, at-home ketamine sessions may be paired with virtual psychotherapy. It varies by which company you go with but you might, for example, be screened on a video call and then paired with a nurse practitioner or clinician to go over dosage and protocol.
What does it feel like?
During the session, it feels like “a dream you can control” according to one Redditor who tried ketamine-assisted psychotherapy for severe anxiety and depression.
“You can steer your mind in different directions, as you’re still cognitive and rational, and you can even move thoughts around with your hands, head and eye movements,” they wrote in the r/TherapeuticKetamine subreddit. “It’s unique. It’s like you’re the maestro of your own thoughts.”
“Ketamine infusions are completed in the presence of a therapist and qualified doctors, who will note down any things discussed during the session,” Walters says. The next day, you’ll return to the clinic for another talk therapy session.
Who Benefits Most from Ketamine-Assisted Psychotherapy?
“A good potential candidate for KAP sessions is somebody who suffers from treatment-resistant depression, anxiety, OCD or PTSD and who hasn’t achieved positive benefits from traditional methods such as CBT sessions or antidepressant medications,” Walters explains.
Ketamine-assisted psychotherapy is highly effective in treating depression and PTSD by decreasing suicidal ideation, compulsions, and anxiety, according to a 2022 clinical review that included data from over 600 patients (8). Ketamine may also support patients who have unexplainable or neurological chronic pain conditions.
Research has yet to identify one ketamine protocol as more beneficial over another (9). This means that the clinician you partner with may have to adjust your dose of ketamine, timing, and therapy depending on initial results.
How long does it last?
The effects of ketamine will last for about an hour after the drug kicks in.
Several Redditors report feeling relief from their anxiety and depression immediately after the first session. However, others opt for multiple sessions if they feel they need to work through more persistent mental health issues. For those who need multiple sessions to see lasting improvements, research suggests that the positive outcomes may last up to a month after the final session (10). It all depends on the ketamine treatment plan that you and your clinician agree upon.
Risks and side effects of ketamine-assisted psychotherapy
There are a few conditions—like active psychosis or active substance use—that would disqualify you from taking part in ketamine infusions.
Some physical health problems also make ketamine infusions a high risk, such as unstable blood pressure or heart disease, explains Walters. Some patients undergoing treatment experience nausea, dizziness, double vision, drowsiness, and confusion. Ketamine use has also been reported to cause an increase in blood pressure and heart rate, and may result in hallucinations and feelings of detachment.
According to the DEA, a ketamine overdose can cause unconsciousness and dangerously slowed breathing, and the long-term effects of its use as an antidepressant are still unknown.
“Medically speaking, ketamine is a very safe drug, however there are contraindications,” Sabbagh says. He notes high blood pressure, a history of substance abuse, a history of cystitis, and personality disorders as issues to flag, and which may be contraindications.
How Much Does Ketamine-Assisted Psychotherapy Cost?
Walters notes that ketamine-assisted psychotherapy is not a “traditional” treatment, and therefore, is not always covered by insurance. However, she recommends reaching out to your insurance to see if they’ll cover the treatment.
In the United States, single, in-person ketamine-assisted psychotherapy sessions cost between $400 and $2,000, according to the Ketamine Clinics Directory. Online ketamine clinic Mindbloom charges around $200 per session, with packages starting at six sessions. Another virtual clinic, Joyous will run you $130 a month.
Where to Find Ketamine Infusion Therapy
There is no shortage of clinics offering ketamine-assisted therapy, Sabbagh’s Journey Clinical included. To find one near you, check out the American Society of Ketamine Physicians, Psychotherapists, & Practitioners, a nonprofit whose members adhere to a strict set of standards and ethics, and who are dedicated to the safe clinical use of ketamine for mental health disorders and pain conditions.
Ask the clinic you choose about their delivery methods, whether or not they combine treatment with in-person therapy, and whether or not it is covered by insurance. Ketamine infusion therapy is fairly expensive, and is not always covered by insurance, so contact your provider for more information.
References
1. Anand, Amit, et al. (2023). Ketamine versus ECT for Nonpyschotic Treatment-Resistant Major Depression
2 Sattar, et al (2018). A Review of the Mechanism of Antagonism of N-methyl-D-aspartate Receptor by Ketamine in Treatment-resistant Depression.
3. Khoodoruth, et al (2022). Glutamatergic System in Depression and Its Role in Neuromodulatory Techniques Optimization.
4. Abdallah, et al (2020). Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin.
5. Harmer, et al (2017). How do antidepressants work? New perspectives for refining future treatment approaches.
6. Duek, et al (2023). Long term structural and functional neural changes following a single infusion of Ketamine in PTSD.
7. Bottemanne, et al (2021). Ketamine Augmentation of Exposure Response Prevention Therapy for Obsessive-compulsive Disorder.
8. Drozdz, et al (2022). Ketamine Assisted Psychotherapy: A Systematic Narrative Review of the Literature.
9. Mandal, et al (2019). Efficacy of ketamine therapy in the treatment of depression.
