Ketamine and Esketamine Therapy

Ketamine was developed in the 1960s as a novel anesthetic agent with unique properties. In the late 1990s, because of these unique properties, psychiatric researchers became interested in ketamine as a novel antidepressant. For some people with depression, there is a decrease in the number of connections (called “synapses”) between brain cells–ketamine, in a low dose, can help the brain re-grow these connections.

Since 2000, when the initial study of ketamine’s affect on depression was published, interest around its therapeutic application has been growing. For some patients with depression, standard treatment with antidepressant medications, transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT) and psychotherapy prove ineffective or insufficient. In those circumstances ketamine, or its derivative esketamine, has the potential to improve symptoms of depression even where other therapies have been insufficient.

Ketamine vs. Esketamine

The ketamine molecule has two different orientations (much like your hands have two different orientations): a molecule that points to the left (called “levorotatory”) and a molecule that points to the right (called “dextrorotatory”). Ketamine is a mixture of both. Because the dextrorotatory is poorly absorbed through the skin or when taken orally, ketamine (again, a mixture of levorotatory and dextrorotatory molecules) is typically delivered intravenously to make sure an adequate dose is provided. While there is strong evidence of its efficacy in treating depression, the use of ketamine is “off label,” meaning it has not been approved by the FDA for the treatment of depression.

Esketamine, in contrast, is the pure levorotatory molecule. Unlike ketamine, esketamine is absorbable through certain kinds of skin, and so it can be delivered through an intranasal inhalation. Also, unlike ketamine, esketamine has been approved by the FDA for the treatment of depression and suicidality.

Ketamine, on average, has greater proven efficacy in the treatment of depression than esketamine, although presents unique logistical challenges. Read the testimonial of a patient who received ketamine treatment at BWFH.

Logistics

Target Population

Ketamine:

healthy adults (at least 18 years old) with treatment-resistant depression (failure of two adequate trials of antidepressant medications or ECT/TMS)

Esketamine:

healthy adults (at least 18 years old) with treatment resistant depression (failure of two to four adequate trials of antidepressant medications or ECT/TMS)

Eligibility interview

Ketamine and Esketamine: 1-hour long interview (covered by insurance)

Medical Health

Ketamine:

medical clearance will be provided by the ketamine-providing psychiatrist unless there are special concerns, in which case medical clearance will be provided by your primary care physician

Esketamine:

medical clearance will be provided by the ketamine-providing psychiatrist unless there are special concerns, in which case medical clearance will be provided by your primary care physician; this includes basic lab work, EKG and a physical examination

Treatments

Ketamine:

consists of up to eight treatment sessions, scheduled as two to three infusions per week; further treatments are based on individual patient response and provider recommendations

Esketamine:

Treatments are provided twice weekly for four weeks, weekly for four weeks, then weekly/every other week before a tapering course (at least four months of treatment); treatments last a minimum of two hours

Cost

Ketamine:

$550 per infusion (ketamine is currently not covered by most insurances and should be considered an out-of-pocket expense)

Esketamine:

Esketamine is covered by insurance after prior authorization from the insurance company is obtained; continued treatment requires additional, scheduled, prior authorizations

Monitoring

Ketamine:

Esketamine:

Given its novelty, eligible patients must be enrolled in a “Risk Evaluation and Mitigation Strategy” (REMS) program which is a private monitoring agency that evaluates risks of esketamine as it is provided to the community

Discharge Supervision

Ketamine and Esketamine:

patients will need a responsible adult (friend or family member) to transport and supervise the patient upon discharge. This cannot be a livery service such as Uber, Lyft or a taxi.

Location

Ketamine:

infusions will be performed at Brigham and Women’s Faulkner Hospital in the morning

Esketamine:

infusions will be performed at Brigham and Women’s Faulkner Hospital in the Outpatient Infusion Center on the third floor

Time Allocation

Ketamine:

while the total infusion time is 40 minutes, patients and their accompanying responsible adults should plan one and half to two hours for the total time, including checking in, pre-infusion screening and post-infusion recovery

Esketamine:

after initiation of treatment, a patient is monitored for a minimum of two hours

Referral Process

Ketamine and Esketamine:

referrals must be made through the patient’s providing psychiatrist or psychiatric nurse practitioner

Treatment Approach

Ketamine and esketamine are effective medications for the treatment of depression. That said, they may not work for everyone. At Brigham and Women’s Faulkner Hospital, our treatment approach is trauma informed, patient centered, collaborative and allied with you. We are happy to answer any questions that might help you understand the procedure and help you feel secure in your decision. We will also help you make decisions about ongoing treatment with ketamine and esketamine with regard to dose and frequency of treatments. We also acknowledge the importance of a comfortable setting in which to undergo these treatments and work with patients to prepare for the infusion or intranasal inhalation of these medications.

Referring psychiatrist/psychiatric nurse practitioner:

If you are in the Mass General Brigham network, please use the AMB REFERRAL TO BWFH PSYCH INTERVENTIONS (REF5111) order in the Epic EMR.
For providers outside the network, please complete this form (also available as a Word doc) and fax it to 617-983-4688. If you have any questions, contact Psychiatry Interventions at 617-983-7973.

Thank you for considering Brigham and Women’s Faulkner Hospital as your partner in collaborating in your care.

Department of Psychiatry

Ketamine and Esketamine Therapy

Ketamine vs. Esketamine

Logistics

Treatment Approach

Referring psychiatrist/psychiatric nurse practitioner:

Our Services

Brigham and Women's Faulkner Hospital