What is ketamine? How is it used to treat depression and how does it work?

Ketamine is a long used anesthetic medication that has recently been found to be helpful for treating depression, even in individuals who have not responded to other interventions.  It can be administered in a variety of ways: via an intravenous ketamine infusion (IV), an intramuscular injection (IM), intranasally, sublingually, or even orally.  It is unique in that it works very rapidly, with individuals frequently seeing improvement in their depression within hours.  Ketamine administrations take place only in clinic and are medically monitored by Dr. Ryan the entire time.  These treatments take place in the psychotherapy suite, which makes for a more comfortable environment than a hospital post-op room, as is done in many other clinics.  These 90 minute ketamine sessions include several components: medication management, ketamine administration, and psychotherapy, and can be combined with regular ongoing follow-up visits.

What about ketamine-assisted psychotherapy?

Combining ketamine with psychotherapy, as done here, can yield an even greater benefit than ketamine treatments alone.  The psychedelic aspects of the ketamine experience provide for more material to work with in therapy, especially in the context of a long term psychotherapeutic relationship. While studies examining this particular application of ketamine are limited, work with compounds that create similar states of consciousness--such as MDMA, LSD, and psilocybin--suggest a role of altered states and psychotherapy that is independent of the well established biochemical antidepressant effects of ketamine.  Research into applications of the so called "classical hallucinogens" (LSD, psilocybin, mescaline, DMT, ayahuasca) drastically slowed in the 1970s due to political pressure, but have in recent years resumed with promising preliminary findings.  Similarly, the well known entheogen MDMA (methylenedioxymethamphetamine), which is one of the active ingredients of the street drugs molly and ecstasy, was used by psychiatrists in the 1980s to augment psychotherapy.  Results were quite promising, but research essentially halted after the DEA scheduled MDMA as a controlled substance in 1985, resuming only recently. Studies of MDMA-assisted psychotherapy suggest efficacy in treatment of PTSD, even in individuals who exhausted all other available treatment methods. Perhaps most exciting is the study that suggests benefits from such assisted psychotherapy last for years after the initial course of therapy, as seen in Mithoefer's landmark follow up study.  Ultimately, patients who undergo ketamine sessions are encouraged to continue with or begin their own psychotherapy, though this is not an absolute requirement to treatment.  Individuals with an existing therapist are welcome to continue seeing them, and those without have the option to be seen by Dr. Ryan for psychotherapy.  

Should I receive ketamine treatments from a psychiatrist or an anesthesiologist?  What are Dr. Ryan's qualifications?

Ketamine treatments are commonly offered by either psychiatrists or anesthesiologists. Both medical specialties have their unique qualifications; while anesthesiologists are well versed in the physiological effects of ketamine, they do not have any psychiatry or psychotherapy training. Psychiatrists, conversely, are extensively trained in psychotherapy, treatment of depression, anxiety disorders, and addiction, and as medical doctors are well qualified to administer sub-anesthetic doses of ketamine. Indeed, doses used in such treatments have a much more favorable safety profile than the higher anesthetic-level doses used in surgery.  A large advantage of receiving your ketamine treatments from a psychiatrist involve the addition of psychotherapy, which boosts efficacy.

Further benefits of having a psychiatrist manage one's ketamine treatments include the option to consolidate all of your psychiatric care with one provider, including medication management / ongoing mental health prescriptions, psychotherapy, and ketamine treatments.  Dr. Ryan is uniquely qualified given his extensive academic, clinical, and research experience, including double board certification in psychiatry and addiction psychiatry, years of psychodynamic psychotherapy and motivational interviewing training, as well as various presentations and publications on treatment of depression, ketamine for treatment resistant depression, MDMA-assisted psychotherapy, cannabis, club drugs, hallucinogens, and addiction. He also has extensive experience working with individuals in altered states of consciousness as a medical/lead at the Zendo Project, which provides psychedelic harm reduction at various festivals.

Is ketamine safe? What are some reasons I would not be eligible (contraindications)?

Ketamine is a unique among anesthetic medications in that it is extremely safe, having been used in various settings for more than fifty years, even in poorly monitored settings such as battlefield anesthesia and developing countries, "ketamine has a good safety profile and is easy to use, especially in under-resourced health systems and emergency settings where clinical conditions and medical equipment are generally not available" (World Health Organization).  Ketamine has an even higher margin of safety when used to treat depression because such doses are much lower than those used in surgery. Patients typically remain conscious the entire time, though may feel somewhat altered and experience perceptual changes.  When used in higher surgical and anesthetic doses, ketamine requires the presence of an anesthesiologist for full airway and cardiac monitoring, while the lower doses used in depression do not.  There are specific reasons you would not be eligible for ketamine, including recent myocardial infarction (heart attack), recent psychosis (hallucinations, delusions), or recent bladder inflammation (cystitis). Administration of ketamine and medical monitoring throughout the session is performed by Dr. Ryan, and not by nurses or personnel with less medical training.   

What is the best route of administration for treatment of depression?

As noted above, ketamine can be administered in several different ways: by an intravenous infusion, an intramuscular injection, intranasally, sublingually, and orally. Intravenous ketamine infusions have been most studied because of their historical use and original FDA approval decades ago, though more and more studies are finding comparable efficacy with the other routes of administration.  It is not clear that intravenous ketamine infusions are more effective than other routes of administration, and further results in great patient discomfort, greater resource utilization, and ultimately result in a higher cost.  For this reason I typically offer ketamine via the intramuscular route, which appears to be non-inferior in terms of efficacy for depression. For an in-depth discussion I invite you to read the review article I authored for the International Journal of Transpersonal Studies: Ketamine and depression: a review.

Am I a good candidate?  How are ketamine treatments structured?

Prior to initiating ketamine treatments, potential patients are scheduled for an initial psychiatric evaluation.  On this first meeting, we will determine a diagnosis, develop a treatment plan, and assess for any medical or psychiatric issues that may interfere with ketamine treatment. If we mutually agree that ketamine could be beneficial, then we can schedule a subsequent visit for the actual administration; with some planning, it is possible for both the intake and administration to be done on the same day.  The greatest benefit of ketamine is attained with multiple administrations over the first few weeks of treatment, which is then followed by periodic booster treatments to maintain freedom from depression.  I ask patients to commit to a series of 6 administrations over 3 weeks, and then return for periodic bimonthly to monthly booster treatments thereafter to prevent depression from returning. Please note, it is always your option to stop treatment at any time. Patients must have a friend or family member pick them up after the appointment, as ketamine temporarily impairs one's ability to drive. Ketamine sessions are scheduled for 90 minutes in duration, and involve a brief medication management visit, the actual ketamine administration, followed by psychotherapy, all of which is integrated into one visit.

For individuals interested in ketamine treatments, please print out the informed consent (see forms page) and bring it with you to our appointment.  I will have you sign it after an in depth discussion about the risks, benefits, and alternatives available to you.

Are there any precautions?

Individuals receiving ketamine should abstain from any food or drink for the 6 hours prior to receiving the medication, and furthermore, should not drive for the remainder of the day. This is a necessary precaution because the subtle after effects of ketamine can linger for hours after the treatment and impair the ability to drive.  Effects typically resolve by the following day, at which time driving is allowed. Typically patients arrange a ride home with a friend or family member, and once tolerability is established can later use a taxi or ride sharing service to return home.

What is the cost of ketamine treatments? Do insurance companies cover it?

I do not directly contract with insurance companies, but instead collect the full fee at time of the visit and provide patients with a superbill that can be submitted to their insurance provider for reimbursement.  Current fees can be found on the new patient intake form, available here.

Visits may be partially covered depending on your insurance plan.  The ketamine administration itself is generally not covered by insurance, however the typical 90 minute long ketamine treatment session involves several other components which may be reimbursed for: the brief medication management (99213, 99214, or 99215) and psychotherapy visit (90833 or 90834) are typically covered by insurance, though this cannot be guaranteed.  In addition, the initial psychiatric evaluation visit (99205) is also typically covered.  I suggest potential patients check with their insurance provider to see what their out-of-network coverage benefits are for the above procedures/CPT codes.  PPO type insurances usually allow for out-of-network benefits, while HMO plans do not.

What can you tell me about the use of ketamine for treatment of addiction or substance use disorders?

Ketamine has been studied for treatment of addiction, specifically to the opiate and street drug, heroin.  Findings suggest that ketamine, as part of a structured therapy program, is effective for the treatment of addiction, perhaps due to biochemical properties as an NMDA receptor antagonist. While studies examining this particular application of ketamine are more limited than those examining treatment of depression, work with compounds that create similar states of consciousness--such as the "classical hallucinogens": LSD, psilocybin, mescaline, DMT, and ayahuasca--suggest a role for altered states independent of the biochemical effects of ketamine.  Such compounds seem to work to treat addiction via their ability to produce spiritual or mystical experiences. While such "classical hallucinogens" are not currently available for clinical use, there exists a growing literature detailing successful and robust treatment of tobacco and alcohol addiction. Use of the aforementioned compounds outside of a research setting is however illegal, except for ketamine which has been FDA approved for other indications and is consequently available for off-label use to treat such diagnoses as depression, post-traumatic stress disorder, and addiction / substance use disorders.

What other psychiatric conditions has ketamine been used for?

Treatment resistant depression is, by far, the most extensively studied psychiatric application of ketamine, and has a wealth of data to support its use.  Other indications (or reasons to use ketamine) include drug or alcohol use disorders (specifically for opioid or cocaine use disorders),  Post-Traumatic Stress Disorder (PTSD), and eating disorders such as anorexia or bulimia.  On the other hand, data suggests ketamine is less effective for treatment of Obsessive-Compulsive Disorder (OCD), but may be worth pursuing on a case by case basis.

Where can I learn more?

You are invited to read a review article I authored on ketamine for depression.  The full text is available free of charge from the California Institute of Integral Studies [ full text ].  An updated version of this review is available as a book chapter in a larger publication on ketamine.  The book, entitled The Ketamine Papers--Science, Therapy and Transformation, is published by the non-profit Multidisciplinary Association for Psychedelic Studies (MAPS) and available for purchase through their website and amazon [ order the book via MAPS, or via amazon ].  Also available is a video recording of a presentation on ketamine that I gave for the Aware Project [ YouTube video ].