Guide to Ketamine Treatments: Understanding the New Approach

“Recent data suggest that ketamine … might be the most important breakthrough in antidepressant treatment in decades.”

Thomas Insel, MD, Former Director, National Institute of Mental Health (NIMH)

It is estimated that 264 million people worldwide suffer from depression. In addition, every 40 seconds a person commits suicide [1]. With staggering statistics like these, it is no wonder thousands of people are searching for new methods of symptom management. In recent years, many people with depression have been turning to ketamine treatment to find relief—although ketamine is not a new drug. Widely known as an anesthetic and club drug, ketamine has been found to have antidepressant properties, bringing hope to people for whom other interventions have been ineffective.

In this Guide:

  • Ketamine Quick Facts 

  • Routes of Administration

  • Three Treatment Approaches with Dosing

  • Ketamine Infusion Clinics Versus Ketamine-Assisted Psychotherapy 

  • Is Ketamine a Fit?

  • Appointment Preparation

  • Post Treatment

  • Controversy in the Industry 

  • Studies

  • Clinics

Ketamine Quick Facts

  • People utilize ketamine to help with depression, chronic pain, PTSD, and anxiety.

  • Ketamine has been shown to help individuals with depression where other treatments have failed. It has proven to help even those who have been diagnosed with “treatment-resistant” depression.

  • Ketamine has been safely used in medicine for six decades.

  • There is strong documentation of ketamine’s benefits for neuropathic pain.

  • There is strong documentation of ketamine’s ability to alleviate depression.

Routes of Administration 

There are several ways to deliver ketamine:

  • Infusion: with an IV

  • Intramuscular (IM): injection with a syringe 

  • Intranasal: sprayed directly into the nose

  • Sublingual: under the tongue, usually as a lozenge 

Three Treatment Approaches with Dosing

The dosing of ketamine is a crucial part of the treatment process. Accordingly, there are three different dosing approaches; two that induce sub-psychedelic states and one that induces a psychedelic state.

Sub-Psychedelic Ketamine Treatment

1) Sub-psychedelic doses of ketamine are often delivered via intravenous infusion. This approach has been endorsed by NIMH and the American Psychiatric Association. The dosage in this treatment is based on body weight. A series of infusions is typically administered, grouped together in a two- or three-week time frame to achieve antidepressant benefits.

In this model, the patient participates in the process significantly less than in other ones. The emphasis here is put on the biochemical action of ketamine, rather than the experiences it can produce. This puts the patient in a passive position in his or her healing, and is the most common model in ketamine clinics.

2) The second method also uses a sub-psychedelic dose, but involves the active participation of the person undergoing the treatment. Typically, the ketamine is given sublingually or as an intramuscular injection in the 0.3–0.8 mg/kg range. The psychological state produced by the ketamine is then used to fascinate psychotherapy. This approach is very similar to MDMA-assisted psychotherapy protocol. Ketamine is used to help the patient talk through topics, traumas, and feelings he or she might otherwise find difficult to confront.

Only a trained psychotherapist is qualified to use this approach. In this model, the healing is thought to occur as a result of the interaction between the chemical’s effects and the psychological processing that accompanies them. Here, both the person undergoing the treatment and the clinician have active roles in the journey towards healing.

Psychedelic Ketamine Treatment

3) The final approach is to intentionally induce a psychedelic therapy experience by administering ketamine via intramuscular injection in the 1.0–2.0 mg/kg dosing range. For safety reasons, this is typically done by a medical professional in a supervised environment. This approach requires proper preparation, as psychedelic experiences can be frightening if the participant is not adequately prepared.

While under the influence of the ketamine, people usually disassociate and may have dreamlike visions. Unlike the other two methods above, this approach values visionary experiences. The clinician’s role is twofold: 1) Ensure the physical and psychological safety of the individual undergoing treatment during the experience; and 2) Help to construct meaning from the experience after it has ended, as well as identify ways to move forward into wellness. 

All three treatment paradigms have value. Determining the best approach depends upon the individual, as well as his/her current needs and goals. Dosing will work differently from person to person, and will depend on what that person is experiencing during that period of time.

Ketamine IM Injection TherapySub-Psychedelic

Ketamine IM injections are administered with a syringe needle in the deltoid muscle of the shoulder or the gluteal muscle of the hip. Some centers providing IM injections will perform follow-up treatment with sublingual treatments. 

Ketamine IM Injection Cost

Depending on the clinic’s location and services, one ketamine injection can range in cost between $300 and $1,500. The average cost of an injection treatment will run about $500 out of pocket. For more information about insurance, see “Insurance Coverage” below. 

Ketamine Infusion Therapy—Sub-psychedelic

A ketamine infusion is a medical procedure, done by a licensed professional either in a medical office or hospital/clinic. Treatment length will vary by condition, severity, and dosing. 

Many ketamine clinics focused on physical pain treatment administer the IV for four hours. This is based on the original protocol of Dr. Schwartzman and his studies on ketamine infusions for complex pain.

Ketamine infusions for treatment of depression and other mental health issues usually last between 40 minutes to two hours, depending upon the patient.

Short-Term Side Effects 

Even in the sub-psychedelic ranges, patients may experience dizziness, fogginess, or nausea. Occasionally, patients experience blurry vision. Side effects tend to diminish in a few hours.

Ketamine Infusion Cost

Cost can vary depending on the clinic location and services offered. Average ketamine infusions run between $400 and $2,000, depending upon the services offered and the provider. The average cost of a ketamine infusion treatment will run about $500 out of pocket. 

Insurance Coverage

Ketamine administered via IV or IM is an off-label treatment, meaning the FDA has not yet approved it as a treatment for depression. For this reason, insurance will not routinely cover ketamine, although insurers sometimes approve it upon appeal for people with chronic mental health difficulties. Depending on your insurance and your ketamine provider, your intake visits may be eligible for coverage. Be sure to speak with your insurance company and ketamine provider before your visit in order to assess what will be paid by your insurance, and which expenses will be out of pocket.

Additionally, be sure to discuss the frequency of your sessions and the number of sessions allowed in a series. This will help you chart the road ahead and allow you to prepare, both for your time and finances.

Insurance companies will likely cover esketamine treatment (low-dose nasal spray) in the near future. However, it is important to know that a Big Pharma company controls the amount and the frequency of your treatment, not the doctor. This kind of treatment is sub-psychedelic by design, and typically does not include concurrent psychotherapy. 

Number of Treatments

The number of ketamine treatments you may need depends on your situation. Some people go monthly for years. Others have a series of five to fifteen sessions to address deep issues, followed by a booster every six months to a year. Other patients have three sessions and then continue their regular talk therapy. Additionally, some people may be seeking out ketamine therapy because they are going through a challenging time in their lives, and one session is enough to reset and move forward. This is such a broad spectrum, which is why the number of treatments depends entirely upon the individual, and his or her provider.

Ketamine Infusion Clinics Versus Ketamine-Assisted Psychotherapy 

Ketamine treatments tend to fall into one of two different approaches. The most widely available one is typically found at ketamine infusion clinics. Such a facility’s administrator must have an MD, but is not required to have training in psychotherapy. Administration of ketamine itself may be done by a medical provider, whether an MD, anesthesiologist, or nurse. No psychotherapeutic work is performed. Any antidepressant effect depends upon the biochemical properties of the ketamine, and the events that play out in the mind of the person undergoing the experience, as well as his or her efforts to make changes in day-to-day life. This approach derives from the symptom-control model of managing depression, in a manner similar to prescribing antidepressant pharmaceuticals like SSRIs. For people who are suicidal, and for others whose primary concern is imminent symptom control—rather than addressing the underlying psychological issue(s) that led to the depression—such clinics can literally be lifesavers.

Another option is ketamine-assisted psychotherapy. This approach is aimed at addressing the root causes of the patient’s depression. Any ketamine clinics that offer psychological treatment alongside ketamine’s administration fall into this category. Attendance at a ketamine infusion clinic, combined with ongoing psychotherapy from an unassociated therapist, is another way to explore this combination. However, this would not involve any psychotherapeutic sessions during an altered state.

Pros and Cons 

Ketamine infusion clinics focus on producing a rapid antidepressant effect, which can save the lives of people suffering with depression. This approach may help them to function more effectively in daily life and to achieve their goals. The downside is that continued treatments will most likely be required, as symptoms will likely return after a time without addressing the underlying causes of the depression.

By aiming to address the root causes of the depression, ketamine-assisted psychotherapy may have a better chance at promoting psychological healing, rather than temporarily suppressing symptoms. This approach requires a more active commitment on the part of the person undergoing the treatment. However, some patients may not feel up to this challenge if their symptoms are sufficiently severe.

Is Ketamine a Fit?

Ketamine can be used as an incredible tool for some people. For others, it isn’t a good fit. If you are considering ketamine treatment, it’s crucial that you’re honest with the provider about your medical history. Prepare questions to ask the doctor and/or staff in order to determine whether or not the facility provides adequate and thorough care. 

If you are already working with a therapist and/or medical doctor, seek their counsel on adding ketamine to your treatment. However, if you are not yet connected with a professional, strongly consider finding a ketamine treatment facility that offers therapy before starting ketamine infusion or IV treatments.

When deciding if ketamine treatment is right for you, be sure to talk to your health care professional concerning:

  • Bipolar/mania episodes

  • Prescriptions

  • Levels of pain

  • Whether you feel more comfortable with a provider of a certain gender identity, and/or one who is trans- and gender-diverse friendly

  • Previous treatment plans

  • Current treatment plan

Questions to ask yourself in order to evaluate the right ketamine provider for you include: 

  • Are you going for pain or mental health issues?

  • Are you requesting someone who offers psychotherapy?

  • Do you want to maintain your relationship with your current therapist, and supplement your plan with a ketamine provider in your area?

  • Do you have a treatment plan?

  • Would you like to work with someone who can help you with an all-encompassing treatment approach?

  • What treatment approach will he or she be using for dosing? Why?

  • Does the provider offer the route of administration you feel comfortable with?

  • Is the setting of the treatment one which allows you to relax?

Ketamine may not be a good fit for you if:

  • You have uncontrolled high blood pressure

  • You have serious heart problems

  • Alcohol or drug dependence is an issue for you

  • Your lung health is poor

    • You have poor general health

    • You are taking certain medications

Ketamine Treatment Plan

When used, ketamine is merely one aspect of any successful approach to treating depression. In order for ketamine treatments to work optimally, they must be viewed as only one part of the treatment plan. Take control of your healing journey, and tailor your treatment to your needs and desired outcome. 

When developing a treatment plan, consider using ketamine in conjunction with:

  • Therapy and/or a support group

  • Medications (always consult your primary care physician and/or psychiatrist for treatment)

  • Healthy lifestyle

    • Diet 

    • Exercise

    • Moderate to no alcohol and/or substance use

    • Regular sleep schedule

  • Mindfulness practices

    • Meditation

    • Breathing exercises 

    • Journaling

  • Purpose 

    • Meaningful work

    • Volunteering 

  • Community

    • Relationships

    • Social interaction

  • Self-Care

    • Hygiene

    • Recreation/Hobbies

    • Self-expression

    • Healthy boundaries

With the help of a mental health care professional, you can build a treatment plan around the areas of your life you most need to focus on, while receiving your ketamine treatments, to achieve optimal benefit from your sessions.

Appointment Preparation 

Your ketamine professional should give you pre- and post-treatment instructions. If he or she does not provide you with any protocol, you may want to reconsider him or her as your provider. Below is some general information and some things to consider. Note: this information is not medical advice.

  • Consider having a physical done prior to your appointment. Check the status of your overall health. This can help monitor your physical health throughout your ketamine treatment plan. 

  • Continue taking your regular medications, and communicate all details of your medication and supplement protocol with your provider.

  • Avoid eating for four hours before your appointment. This will help reduce the chances of nausea.

  • Schedule your treatment on a day you do not have work, and during which you have no other responsibilities. This will give you the opportunity to rest after treatment and, if you wish, to journal and reflect on the material that arises during your session.

  • Patients are not allowed to drive for many hours after ketamine treatment, so you will also need to have a transportation plan. 

Post Treatment

Medication

Keep taking your normal prescriptions in accordance with your provider’s directions. You may feel better in the days or weeks after a treatment. It is important to maintain your regular protocol and not stop taking medications. Deviating from an agreed-upon plan by abruptly stopping antidepressants and/or other medication is not advised.

Tracking

The day after a ketamine infusion or IV treatment, some people feel great, while others feel worse. Some people find relief from symptoms for months, while others do for only a few weeks or days. Due to the vast number of variables involved, providers are unable to anticipate how you will feel in the coming days after the treatments. Being mindful of your emotions and tracking your mood will help you and your doctor with the treatment process.

Keeping a journal is a good idea. Ketamine may trigger old emotions or even bring up repressed memories. Being honest with yourself in how you feel will assist you through the process.

There are also mood apps available that help you quickly and easily track your moods. You may begin to see patterns, such as consistently feeling worse for two days after treatment, but then feeling better for two weeks. This tracking will prepare you more for the changes in mood that each appointment produces. The tracking can also help your provider refine his or her dosing, make decisions regarding treatment frequency, and know when you may need more support.

Whether a journal, mood app, or some other option, find a mood tracking method that works for you and stick with it.

Stick to the Plan

Ketamine won’t do the work for you. Once again, the ketamine itself should only be a fraction of the plan.The rest will be up to you. It is crucial to stick with your treatment plan. Eat healthfully and create an exercise routine. Continue your therapy and ketamine treatments. Reach out for help when you need it.

Controversy in the Industry 

Ketamine has been widely used since the 1960s. It cannot be patented, so it is difficult for pharmaceutical companies to profit from it. While this could result in a cheap and effective therapy for those suffering with depression, the lack of interest on the part of the pharmaceutical companies has made ketamine’s progress through the Food and Drug Administration’s (FDA) regulatory framework slow compared to other treatments for depression. Nevertheless, many doctors have been willing to provide it “off-label” to people in need. Use of a treatment before its successful approval inevitably opens the door to safety concerns.

By producing a molecule that is slightly different from ketamine, but which has similar properties, the pharmaceutical giant Johnson & Johnson has been able to patent a version of this antidepressant treatment. They call this substance esketamine, marketing it as Spravato in the form of a nasal spray. With the backing of Big Pharma, the FDA has already approved esketamine.

In 2019, Donald Trump fast-tracked Spravato at the Department of Veteran Affairs (VA), where there is interest in its use for veterans suffering with depression. Three of Trump’s advisors on the VA—Bruce Moskowitz, Marc Sherman, and Marvel Entertainment CEO Ike Perlmutter—have past involvement with Johnson & Johnson, raising concerns of inappropriate dealings in this matter. Pushing this nascent medicine into the world of politics only serves to increase controversy around the effectiveness and safety of this treatment.

Studies

Ketamine was first found to have antidepressant effects in 2000, in a study conducted at Yale University [2]. NIMH later replicated these results with further studies [3], as did Yale [4]. Current research focuses on elucidating the mechanism of action in the brain that accounts for ketamine’s antidepressant effects, as well as on optimal treatment protocols and ketamine’s effectiveness for specific forms of depression. Ongoing clinical trials can be found at clinicaltrials.gov.

Clinics

A regularly updated list of active clinics can be found at https://ketamineclinicsdirectory.com/ 

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References

[1] https://www.who.int/mental_health/prevention/suicide/suicideprevent/en/

[2] Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry, 47(4), 351–354.

[3] Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., … & Manji, H. K. (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of general psychiatry, 63(8), 856–864.

[4] Krystal, J. H., Sanacora, G., & Duman, R. S. (2013). Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. Biological psychiatry, 73(12), 1133–1141.

James Cooke