Increasingly more people dealing with anxiety, depression, post-traumatic stress disorder (PTSD), and more are turning to ketamine therapy, also known as ketamine-assisted therapy, for its significant therapeutic effects.
Specifically, research suggests that ketamine works quickly and may lead to symptom reduction for some individuals within a few hours. This is a major benefit, especially when compared to traditional treatments which can sometimes take weeks to become effective.
Ketamine therapy can be administered intravenously, intramuscularly, or orally. Additionally, in 2019, the FDA approved a nasal spray known as esketamine, which is particularly effective for those experiencing treatment-resistant depression (TRD), a potentially life-threatening condition.
In this article, we break down how ketamine therapy affects the brain, its efficacy in treating specific conditions, such as anxiety and depression, as well as what the treatment protocol entails. We also discuss the cost of various ketamine therapies, potential side effects, and more.
How Does Ketamine Therapy Work on the Brain?
Ketamine therapy works by stimulating nerves that react to glutamate, a neurotransmitter. Ketamine binds to N-methyl-D-aspartate (NMDA) receptors in the brain, which increases glutamate levels and activates a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Essentially, the new paths formed by the stimulation of NMDA and AMPA receptors allow neurons to communicate along new pathways.
Ketamine’s ability to form new connections between neurons is significant, as certain mental health conditions and long-term stress can cause a loss of these connections, leading to changes in brain functioning and affecting overall quality of life.
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Ketamine Therapy for Depression
Ketamine therapy is considered effective for treating depression, especially TRD, which describes depression that has not responded to at least two traditional antidepressant treatments. The majority of ketamine research has been done on the FDA-approved nasal spray esketamine, under the brand name Spravato. This nasal spray is used to help manage the symptoms of TRD when taken along with oral antidepressants, and requires appropriate medical supervision.
Research on the nasal spray esketamine has shown that:
- It has a statistically significant effect on decreasing the severity of depressive symptoms.
- Its antidepressant effect occurred as soon as two days after starting treatment for certain individuals.
- Compared to individuals using a placebo, or sham, nasal spray treatment, along with an oral antidepressant, those using esketamine experienced a statistically significant longer amount of time before experiencing recurrent depressive symptoms.
Additionally, research on intravenous and injectable ketamine for the treatment of depression notes that its antidepressant effects peak around 24 hours post-treatment and last for up to a week. However, it also showed significant antidepressant effects within one hour after treatment. Other studies have found that oral, intravenous, and injectable ketamine can have short-term anti-suicidal properties independent of reduced depression symptoms, with effects lasting up to 28 days post-treatment.
Other studies have found that some individuals experience favorable effects within one to four hours after treatment begins, and repeated ketamine treatment may reduce depression-related symptoms for up to three weeks.
Ketamine Therapy for Anxiety
Ketamine-assisted therapy may also be effective for treating certain anxiety conditions. Like with TRD, anxiety conditions that have not responded to multiple first-line treatments may show significant improvement after ketamine therapy.
Specifically, research has found that:
- Ketamine therapy temporarily reduced anxiety symptoms for approximately one week post-treatment, when administered once a week via injection for three weeks.
- Ketamine has a fast onset of action, with some individuals feeling a reduction in anxiety symptoms within an hour post-treatment.
- Once or twice weekly ketamine injections showed an immediate effect on anxiety symptoms and progressively reduced symptoms over time when administered over 14 weeks.
- Ketamine may significantly reduce symptoms of social anxiety disorder when administered intravenously, with about 89% of the study’s participants noting a symptom reduction of greater than 50%.
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Other Ketamine Benefits
While ketamine therapy has primarily focused treating depressive and anxiety conditions, there is a growing body of research that suggests its potential use for helping to manage other conditions and concerns, including:
- Obsessive compulsive disorder (OCD), which describes a condition in which an individual experiences uncontrollable, persistent thoughts, and/or repetitive behaviors, which may be used to reduce the stress associated with the thoughts
- PTSD, a trauma and stressor-related condition that involves intrusive thoughts, attempts to avoid the thoughts, as well as changes in cognition and mood
- Alcohol use disorder and substance use disorder, specifically involving cocaine and heroin
- Certain eating disorders
- Super refractory status epilepticus, a life-threatening type of seizure that lasts for 24 hours or longer
- Chronic regional pain syndrome (CRPS), which describes long-term pain that typically impacts the arm, hand, leg, or foot following an injury or surgery
- Bipolar disorder, as long as treatment is coupled with mood stabilization
- Certain personality disorders, if coupled with psychotherapy
What Is Ketamine-Assisted Psychotherapy?
Ketamine-assisted psychotherapy refers to the process of administering ketamine to an individual to treat a condition such as TRD, anxiety, OCD, and PTSD, and coupling it with psychotherapy, or talk therapy. Combining ketamine treatment with psychotherapy may provide additional benefits, notably, better treatment outcomes in some individuals.
Some psychotherapies that may be used alongside ketamine therapy may include:
- Mindfulness-based relapse prevention, a manualized treatment that combines stress reduction skills, cognitive behavioral therapy (CBT), and mindfulness
- CBT, which focuses on how thoughts, beliefs, behaviors, and emotions impact each other
- Ketamine psychedelic therapy, a protocol developed for treating substance-use disorder
- Motivational interviewing, a therapeutic technique used to promote internal motivation
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During ketamine treatment, some individuals may opt to listen to relaxing music. Some people may also want to journal after the session to further help them process their emotions and develop new insights, which can be discussed further during their therapy session.
Ketamine can be administered intravenously, intramuscularly, or via a nasal spray in a clinic under the direction and supervision of a licensed physician. However, ketamine-assisted therapy has become more accessible for those who prefer a more private setting. Ketamine tablets can be administered at home, but the correct protocol must be followed for safe and effective results.
Ketamine-Assisted Psychotherapy Protocol
Before undergoing ketamine-assisted psychotherapy, it’s important to consult with your healthcare provider to see if it’s a suitable treatment for you. It is typically only recommended if at least two traditional treatments haven’t provided enough of an effect. Keep in mind that ketamine therapy will not be recommended for those with active substance use, a history of certain conditions, like psychosis, or who are pregnant or breastfeeding. Most providers will assess medical and substance use history to determine candidate eligibility.
Ketamine-assisted psychotherapy sessions typically last 40 to 60 minutes. In a clinical setting, the individual is given an intravenous or intramuscular dose and instructed to sit or lie down comfortably. Music is often played to help the individual relax, and a clinician observes and records anything noteworthy during the session. Esketamine, the nasal spray, can also be administered in a clinical setting where the individual is under the supervision of a physician for about two hours after the dose.
In some cases, the individual will engage in a psychotherapy session during the time of ketamine dosing. In other cases psychotherapy sessions may be scheduled right before ketamine dosing and about 24 hours after. The timing and frequency of the psychotherapy sessions will largely depend on the client and their needs.
At-Home Ketamine-Assisted Psychotherapy Protocol
At-home ketamine psychotherapy is a bit different than in-clinic treatment. Telehealth platforms allow users to consult a physician through a video call to determine if ketamine-assisted psychotherapy is appropriate. Once approved, a behavioral coach guides the individual every step of the way and provides support via text message. In some cases, about four weekly ketamine therapy sessions occur, where the individual is encouraged to listen to music for about an hour, while lying in a comfortable position.
Afterwards, individuals are encouraged to journal about the experience, which can be further processed in a psychotherapy session. In addition, individuals may be given a digital blood pressure cuff to monitor their blood pressure after every session.
Types of Ketamine Therapy
There are four types of ketamine therapy methods available: intravenous, intramuscular, intranasal, and oral. Intravenous is the standard treatment method, but oral and intranasal treatments are becoming increasingly more common because of their accessibility and ease of use. Intravenous and intranasal ketamine therapy have been the most extensively studied, however, in general, some research suggests similar effectiveness and tolerability of all ketamine forms, but this is dose dependent and more research is still needed.
It’s worth noting that dissociation occurs more frequently with ketamine infusion methods, and while it can happen with tablets and lozenges, the effects are typically much more moderate. It’s also important to note that 100% bioavailability, the actual amount of medication your body can use, can only be achieved intravenously, which typically means a smaller dose of medication is needed.
I.V. vs. Oral Ketamine
Standard dose of ketamine
Onset of action
When do the effects wear off?
Number of treatments
-About 3-6 infusions over the course of several weeks, but can vary
-Daily if low-dose
-About 6 treatments 1-2 times a week for 4-6 weeks
How Much Does Ketamine Therapy Cost?
Ketamine therapy cost varies depending on the treatment method, provider, and session frequency. However, you can expect to pay about $225-$800 per session. If you have insurance coverage, you may be eligible for reimbursement, but it’s best to contact your insurance provider beforehand to find out the details of your coverage.
Ketamine Therapy Side Effects
Short-term effects of ketamine-assisted psychotherapy may include stress from processing emotions or memories, as well as feeling disconnected and possibly more emotionally sensitive. Following treatment protocols and reaching out to your healthcare provider and/or mental health clinician is vital in preventing adverse short-term and long-term side effects.
Ketamine side effects that may occur during and after treatment can include:
- Loss of motor coordination
- Increased blood pressure and heart rate
Some of the more serious long-term effects can include liver damage, gallbladder inflammation, and memory loss.
Who Is Not a Good Candidate for Ketamine Therapy?
Ketamine therapy may not be appropriate for:
- Individuals who have been diagnosed with psychosis or schizophrenia
- Pregnant or breastfeeding individuals
- Individuals with active substance use
- Those with uncontrolled hypertension, or high blood pressure
- Those with cardiovascular, or heart, conditions
- Anyone who has had a negative reaction to ketamine in the past
Ketamine therapy is not appropriate for everyone, making it crucial to discuss your health and medication history with your healthcare provider prior to trying this treatment. In general, ketamine therapy has been used to mainly treat individuals who have been diagnosed with anxiety and/or depressive conditions, however, more research is still needed. In addition, it is not considered a first line of treatment and is typically only recommended if at least two traditional treatments have been attempted, with limited or no effect.
Some supplements and medications should not be taken in conjunction with ketamine therapy, including:
- Benzodiazepines, a type of depressant drug
- Lamotrigine, an anti-seizure medication
- Memantine, a medication for dementia
- Other drugs affecting NMDA receptors
Prior to trying ketamine therapy, be sure to let your healthcare provider know about any health conditions you may have, as well as any prescription or over-the-counter (OTC) drugs, supplements, or vitamins you are taking.
Ketamine Therapy Reviews
Ketamine therapy will yield different results for every individual, but commonly reported experiences include feelings of dissociation, calmness, and a dream-like state.
Ketamine therapy may be an appropriate treatment option for individuals experiencing certain mental health conditions, including depression, anxiety, PTSD, and more who have not had the symptom reduction they were hoping for with more traditional treatments. For those who have been approved for treatment by their healthcare providers, it’s considered to be a generally safe and effective option that offers many benefits and reduced risks compared to certain medications. As with any treatment, though, there are potential risks and side effects to be aware of, including nausea, headaches, dizziness, and more.
Ketamine-assisted therapy is still a relatively new treatment, but it’s becoming increasingly popular for those who want an alternative to prescription antidepressant or anti-anxiety drugs, especially because of its fast-acting effects. While more research still needs to be done concerning the long-term effects and the efficacy of it, ketamine therapy is moving towards becoming a more standardized treatment option for certain mental health conditions.
In many cases, insurance will not cover certain types of ketamine therapy, especially intravenous, injections, and oral medications, as they are prescribed off-label. However, sometimes there are exceptions, so it’s best to contact your insurance provider to review your policy.
Each Ketamine therapy session lasts approximately one hour, while a complete treatment program can last anywhere from a few weeks to several months. In some cases, individuals opt for additional treatment, or booster sessions as needed.
Yes, you need a prescription for ketamine. However, ketamine is not considered a first-line treatment, so getting a prescription may be difficult unless other treatments have proven ineffective.
A healthcare provider will only approve ketamine treatment for those who are at least 18 years old.
Ketamine therapy may feel like a psychedelic drug experience, a calm, relaxed experience, or an intense emotional experience. However, the exact experience will depend on the individual, the dosage, and the form of ketamine.
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