Ketamine Infusion, Injection, Nasal Spray, or Oral Lozenge: Which Treatment is Best?

In recent years, ketamine has exploded onto the mental health scene due in large part to a groundswell of positive scientific studies. However, not all forms of ketamine are equally effective or safe. In this blog series, Dr. Karen Giles at Breakthru Psychiatric Solutions explores the route of administration and the environment of administration as two primary issues for ketamine treatments.

In this first article, Dr. Giles breaks down the varying routes of administration and their risks and benefits for those suffering from chronic, treatment-resistant depression.

Ketamine was initially developed and FDA-approved as an anesthetic, however, over the last two decades scientists have been studying its rapid and positive effects on treatment-resistant depression and anxiety. Studies have shown it can reduce thoughts of suicide and improve symptoms of treatment-resistant depression.

Previously, the mental health field had to rely on prescription medications and psychotherapy to treat depression and anxiety. The major drawbacks to prescription medications are that they can take quite a while to work (up to 8 weeks in many cases), and they often have significant side effects that make long-term usage untenable. Psychotherapy also takes months to years to have an appreciable effect.

In contrast, ketamine works by rapidly improving the brain's neuroplasticity. A single dose of ketamine has the potential to:

produce antidepressant actions the same day as treatment
lead to resolution of suicidal ideation within hours
reverse depressive behaviors caused by stress
increase synapse function and reverse synaptic deficits caused by stress.

Ketamine treatments are typically given 2-3 times per week for 3 weeks, and then decreased according to your response to treatment, with the goal of one treatment per month.

There are 4 routes of administration of ketamine readily available for mental health patients - intravenous (IV) infusion, intramuscular (IM) injection, intranasal spray, and oral lozenges (troches). All formulations are considered “off-label” use of ketamine, except for Spravato (esketamine), which is FDA-approved for treatment resistant depression and depression with suicidal ideation.

All forms of ketamine carry low-level risks of side effects that are present only during treatment, including:

dissociation
tachycardia
hypertension
nausea
headache
dizziness

Unmonitored, high doses of ketamine can result in more severe adverse effects.

Intravenous (IV) Ketamine:

Ketamine IV infusion occurs in a medical clinic and involves the placement of a needle in an arm vein. The needle connects via tube to a bag of ketamine solution which drips steadily, infusing a specialized dose of ketamine into the vein over 40-60 minutes. IV infusion allows for optimal control of the treatment, as the ketamine directly enters the bloodstream at a carefully controlled rate. This provides for safe dosing with the ability to slow down or stop treatment in the event of adverse effects. IV treatments are monitored by professional medical staff, ideally by a physician, as is the case at Breakthru Psychiatric Solutions. While IV ketamine treatments are not FDA-approved, the treatments have been highly studied in the medical field and are considered very safe when offered under direct medical supervision.

Intramuscular (IM) Ketamine:

Intramuscular ketamine is administered in a clinic setting by injection of a bolus of ketamine via a needle and syringe through the skin and into the muscle of the arm with monitoring for a set period of time afterwards (often at the discretion of the medical team). Once the ketamine is injected, it cannot be removed, slowed down, or stopped. While intramuscular ketamine is technically easier to administer than by IV, in the event of an adverse reaction, there is no way to intervene other than supportive care, because the ketamine is injected all at once. Additionally, it is more difficult to predict exactly how much ketamine will be absorbed from the muscle into the bloodstream, which opens the door to either not receiving enough ketamine or potentially receiving too much and having side effects, which can be dangerous.

Dr. Giles therefore prefers IV ketamine infusions, as the treatments can be slowed down or stopped and do not require absorption from the muscle into the bloodstream.

Intranasal Ketamine:

There are two intranasal formulations of ketamine available in the U.S. at this time, however only one formulation, esketamine (Spravato), is FDA-approved.

Esketamine Nasal Spray (Spravato) is a purified formulation of ketamine (esketamine) that is administered via nasal spray. Spravato is required to be done in a certified treatment center with two hours of monitoring by professional medical staff and the direct supervision of a psychiatrist.

Racemic Ketamine Nasal spray consists of the same ketamine as used in IV/IM treatments that has been formulated into a nasal spray by a compounding pharmacy. These intranasal formulations were developed before Spravato was available and as a less invasive way to receive treatment (thereby avoiding injections and infusions). Intranasal racemic ketamine is often provided for at-home use, however, the FDA recently issued a warning that intranasal racemic ketamine should no longer be used due to safety concerns.

Oral Ketamine:

At home ketamine lozenges (also referred to as troches) are sometimes prescribed through telehealth or in person medical services. Oral ketamine was developed as a more convenient method of treating mental health conditions and is self-administered. Oral ketamine is absorbed through the oral mucosa, which makes it difficult to predict how much ketamine is absorbed into the bloodstream, thereby increasing the risk of adverse events and side effects. Because of its convenience and limited regulation, oral ketamine has been prescribed more broadly for mental health conditions, despite having significantly less scientific data on the safety and efficacy of oral ketamine. Additionally, when taken at home, there is no ability to be monitored for the same adverse reactions and side effects that can occur with IV/IM ketamine. Unfortunately, at-home formulations of ketamine (oral and nasal spray) have led some people to develop ketamine addiction and diversion of the medication. Dr. Giles and many psychiatrists in the field strongly caution against at-home ketamine treatments.

Dr. Giles specializes in interventional treatments such as ketamine IV infusions and Spravato for chronic and treatment-resistant depression. In order to determine the safest, most effective path towards healing, Dr. Giles offers a comprehensive psychiatric exam to every client that visits Breakthru Psychiatric Solutions. Contact us online or by phone to schedule a consultation with Dr. Giles and find out if ketamine or Spravato can resolve your anxiety and depression today.