Summary: Ketamine and Spravato® help treatment resistant depression by delivering a potent medication with antidepressant properties in a safe and effective manner, providing fast-acting symptom relief when standard antidepressant medications are ineffective.
Key Points
- Ketamine was originally approved as an anesthetic in 1970.
- In the 2010s, researchers began examining ketamine for use in depression treatment.
- In 2019, the Food and Drug Administration approved a ketamine derivative, esketamine, for patients with treatment resistant depression (TRD), under the brand name Spravato®
- Both ketamine and esketamine are identified as dissociative anesthetics that have fast-acting antidepressant properties
Ketamine and Spravato® for Treatment Resistant Depression
Millions of people in the U.S. and around the world have depression. The latest estimates show that in the U.S., just over 21 million adults 18+ have major depressive disorder (MDD), and worldwide, around 330 million adults report depressive symptoms and/or clinical depression.
The traditional, standard approaches to treatment for MDD include:
- Medication, such as antidepressants
- Psychotherapy, such as cognitive behavioral therapy (CBT) and dialectical behavior therapy (DBT)
- Education, such as training in life skills related to daily tasks, and instructive workshops on finding and keeping gainful employment when ready
- Adjunct services, such lifestyle changes, peer and family support, and various modalities that support the components of a typical treatment plan.
These approaches work for most people with MDD. However, evidence shows that for around one third of people diagnosed with a depressive disorder, these standard treatments are not effective.
Innovative Therapies: Ketamine and Spravato® Can Help Treatment Resistant Depression
Mental health professionals describe depressive disorders that don’t respond to traditional therapeutic modes as treatment-resistant depression, also known as TRD.
For individuals diagnosed with treatment resistant depression, an expanding evidence base shows that treatment with ketamine can help alleviate symptoms. Data indicates that, in some individuals, ketamine can:
- Reduce depressive symptoms within a short period of time:
- Patients report positive symptom reduction, compared to placebo, within 40 minutes of treatment
- Produce positive symptom reduction that persists for:
- One hour, as reported in three studies
- 2 hours, as reported in three studies
- 4 hours, as reported in five studies
- One day, as reported in six studies
- 2 days, as reported in 4 studies
- One week, as reported in 5 studies
- 2 weeks, as reported in six studies
- 3 weeks, as reported in one study
- 4 weeks, as reported in two studies
Please access the source material for the studies mentioned in this list by navigating to the link above, which lands on a journal article called “Ketamine and Depression: A Narrative Review” published in 2019. In addition, studies published here and here expand the evidence base that show how ketamine and Spravato® help people with treatment resistant deperession.
We won’t spin this data: several studies found no symptom reduction after the four-week point. With that said, people with treatment-resistant depression report that four weeks of reduced symptoms is a positive outcome, compared to little or no relief with a traditional, standard course of treatment involving medication, psychotherapy, and education.
How Ketamine Works: Mechanism, Administration and Dosage
Mechanism of Action
Research scientists indicate that ketamine, a medication initially developed as an anesthetic, which many people may recognize as a common veterinary drug, can relieve the symptoms of treatment resistant depression in doses far lower than those used for ketamine as an anesthetic. Whereas typical antidepression medications, called antidepressants, reduce the symptoms of depression by increasing the amount of serotonin in the brain, ketamine works by increasing the number of receptors in brain cells that bind to a chemical called glutamate.
Some studies implicate the opioid receptor system in the human brain in the antidepressant action, but this evidence is new, and the contribution of the opioid system to the positive effects of ketamine on depression are unclear. Current research seeks to clarify this question. To date, though, no studies indicate therapeutic use of ketamine is associated with the misuse or disordered use of opioids.
Administration
There are two primary ways to administer ketamine for treatment-resistant depression:
- Infusion, which means an intravenous (IV) injection which, rather than a brief shot that takes seconds, occurs over the course of around 40 minutes.
- Ketamine infusion may occur with only one infusion, and achieve positive effects
- After an initial dose, ketamine infusion may occur once or twice a week for as long as four to six weeks
- In some cases, patients respond well to a single dose, while in other cases, patients report symptom improvement after six infusions over a month to three weeks
Response to ketamine depends on the patient. Clinicians and patients determine the optimal regimen –dosage, frequency, duration of the infusion session – based on previous treatment history, the results of an intake assessment, and the effect of the initial doses of ketamine on depressive symptoms.
- Oral administration with liquid ketamine, which is a slightly different form of ketamine called esketamine
- Oral administration may occur once, daily, every other day, or weekly, depending on clinical evaluation of the effect for each patient
- Nasal administration – like a decongestant/allergy spray – of esketamine is available in a formulation with the commercial name Spravato®. This method is approved for therapeutic use only under the direct supervision of a healthcare provider.
- Nasal administration of Spravato® most often occurs alongside simultaneous use of oral an oral antidepressant
- In the first phase of treatment with Spravato®, patients receive the nasal spray twice a week. This phase typically lasts a month
- In the second phase of treatment with Spravato®, patients receive the nasal spray once a week. This phase typically lasts another month.
- In the third phase of treatment with Spravato® – typically after 8-9 weeks, patients receive the nasal spray every other week
In all cases, dosage frequency and duration for Spravato® will vary by patient, results, and clinician evaluation.
The Consequences of Untreated Treatment-Resistant Depression (TRD)
People with TRD may lose faith that any type of treatment or standard therapy will help ease their symptoms and allow them to return to a full, fulfilling, and independent life. That’s why therapies like IV ketamine and intranasal Spravato® are important for people with depression to know about and consider a viable treatment options.
However, one aspect of treatment with these medications – Spravato® is FDA-approved for TRD, while IV ketamine is used off-label for TRD – typically elicits the following question:
Why would a medical team I trust advise the off-label use of a medication?
Here’s how the FDA answers that question:
“From the FDA perspective, once the FDA approves a drug, healthcare providers generally may prescribe the drug for an unapproved use when they judge that it is medically appropriate for their patient.”
Off-label use is common in three circumstances. First, a provider may recommend more than a typical dose, if the typical dose is not effective. Second, there may not be any approved medications for a specific condition. Third, if you’ve tried all other approved medications for your conditions without success, your physician may recommend an approved medication for off-label use.
That last example is true for TRD treatment with intranasal Spravato®. They symptoms of untreated depression can make life very difficult. If you have TRD, you know this firsthand. Depression can impair your relationships, your work life, your family life, your academic pursuits, and your desire to participate in hobbies and activities you love. In short, serious TRD can interrupt, disrupt, or completely prevent most things you do or need to do in your daily life.
That’s why we may recommend Spravato® after discussing all of the information above with you: o you can avoid the negative consequences of untreated TRD. Spravato® has the potential to give you relief from symptoms that may have caused you significant emotional and psychological distress or pain for months, decades, or even years.
In other words, it can work when nothing else has – and when it does work, it can be a lifechanging experience for people with TRD.
Learn More: Call Us at Crownview Psychiatric Institute
If you or someone in your family has been struggling with acute symptoms of treatment-resistant depression, the IV ketamine or intranasal Spravato®: may be an appropriate treatment that can bring relief from severe TRD symptoms quickly.
Learn how we can help:
Gianna Melendez
Jodie Dahl, CpHT