Paradigms of Ketamine Therapy

In the world of ketamine treatment, a potential patient will find a vast array of treatment options. It can be confusing, especially in such a vulnerable state. Today I’ll outline the common methods of administration and philosophies surrounding ketamine therapy.


Mindset and Treatment setting


Because of its often unpredictable psychoactive effects, the setting in which ketamine is delivered can vastly change the course of treatment. When given in a sterile, noisy, chaotic operating room, patients describe a ‘dysphoric’ and scary experience. But when given in a calm, quiet, home-like setting, with a supportive caregiver (or guide) the experience is much more euphoric and enlightening.


Equally important is the mindset of the patient coming into therapy. Nobody seeks ketamine therapy because their inner state is a zen-like garden of order. But understanding why you’re seeking treatment, having clear goals, and a humble expectation of success is important. Unless a patient is imminently suicidal, I encourage patients to wait several weeks before initiating therapy. Preparatory guidance about expectations, working with a patient’s therapist, and the initiation of a meditation practice can make or break the success of ketamine therapy.


High-dose vs low-dose


This is an area of divergence among ketamine practitioners. High-dose therapy (>0.5mg/kg) has the goal of inducing a dissociative state. Patients often describe being out of body, having insights, dreams, visions, or what we sometimes call a ‘mystical’ experience. The goal here is to separate a patient from their circular, ruminative thought patterns. The high-dose method is practically similar to shamanism of indigenous societies. The medication is given over the course of an hour, but time is distorted and the experience can feel like several lifetimes. Visual changes are common– some patients describe fractal patterns, colors, or other interesting shapes.


High-dose therapy depends greatly on the set and setting of therapy. The experience is often more anxiety-provoking, but the potential success may be greater. Insights into the patient’s mental blocks and triggers are often brought to light this way. But high-dose therapy isn’t for everyone, especially for patients who do not want to challenge limiting beliefs.


Low-dose therapy (<0.5mg/kg) is probably the most-practiced method. It reliably produces sedation, euphoria, and transient depression relief. The patient is awake the entire time. Visual changes may happen, but they aren’t as grandiose. Some insights may occur. Low-dose therapy is typically psycho-lytic, in that some of the protective walls around the psyche may be relaxed for a brief time. This experience works well with psychotherapy at the same time as the treatment, as the patient is aware and can work through issues with the therapist. The set and setting are important during low-dose therapy, as it can still trigger a bad experience if the patient isn’t in a supportive environment.


Routes of Administration


The most common method is intravenous, but many practitioners give ketamine intramuscularly. I like to give it IV, as you can reliably induce a dissociatiive state. Also, you can stop the treatment if it becomes too challenging for the patient. IM injections have the advantage of being less expensive and easier to administer for non-anesthetists, but once the medication is given it can’t be stopped. Drug absorption is similar between IM and IV, so the effects will be similar. I will often administer IM ketamine to patients if they’ve had several IV infusions and have tolerated it well. Some patients have poor veins, so IM injections are the only method available.


Intranasal Ketamine


This year the FDA approved Spravato (esketamine) for use in treatment-resistant depression. It seems to be an effective method of delivering ketamine, but it hasn’t been used widely due to its high cost (about 200 times more expensive than generic ketamine). Payment models are evolving, however, and we expect that Spravato will become more common in the future.

The nasal spray route presents some challenges. If a patient has a cold, sinusitus, or allergies, the absorption will be variable. You don’t know exactly how much the patient will get, so you have to be flexible with expectations. Spravato comes in one bottle of 28mg, so you’re kind of stuck with what you get. That said, it seems to work better than placebo for treating depression.


Treatment course


Most providers, no matter how they administer the drug and in what dose, advocate an induction phase ranging from 1-4 weeks. Ketamine is given 2-3 times/week for 1-2 weeks. This acts as a reset to unproductive mental pathways and can give the patient a respite in which they have a more clear-headed view toward life. After the initial induction phase, maintenance treatments are spaced out depending on how the patient responds. If a patient hasn’t responded after 3-4 treatments, it’s unlikely that further treatments will be beneficial.


Medication vs psychology vs spirituality


Ketamine works via a different mechanism than other antidepressants. It blocks the NMDA receptor and it’s glutamate transmitting system. Most of medicine takes the view that depression is a biochemical process and restoring a favorable chemistry will improve depression. The practitioners who deliver low-dose and intranasal ketamine often take this view. Dissociation is seen as something to be avoided. Many patients have been helped in this way. I find low-dose therapy to be transient, however, and symptoms of depression and anxiety usually recur. That said, I’m open-minded about different ways to deliver ketamine. This is an area of medicine in its infancy and will surely evolve as time goes on.


I prefer to use high-dose therapy in patients that are amenable to the process. I find that having a ‘mystical’ experience, a session in which the patient often fails to find words that adequately describe what they’re experiencing, can be a catalyst to progress. When followed by regular psychotherapy, patients can work through the self-limiting beliefs and unproductive coping mechanisms that have been built up over years.


Psychedelic therapy often shares similarities with spiritual experiences. Saints, prophets, mystics, and sages have– for millennia– described other-worldly, rapturous, ineffable, and visually-captivating journeys. Ketamine is often described as a ‘transcending’ experience, wherein we step outside this plane of reality. Going beyond our limited sensory experience of the world. I find it helpful for patients to gain a respect for the unknowable, as ketamine almost universally produces a journey that defies description. When we stop trying to control our inner world, and surrender to the flow of time and space, we become open to the outer world. We treat life as a playground vs a prison.

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