Previously, we discussed some of the newer medications being used and studied for treatment resistant depression. Spravato, or esketamine, was one that was briefly discussed, and since it is FDA approved and more clinics are becoming certified as treatment centers, it seemed worthy of more discussion.

When talking about eligibility for treatment with Spravato, it’s important to understand what treatment resistant depression (TRD) means and if you meet the criteria. Simply put, treatment resistant depression is what it sounds like–depression that does not go into remission after trials of two or more antidepressants. One of the more famous studies often mentioned when talking about TRD is the STAR*D study which was the largest and longest study ever conducted to evaluate depression treatment. The goal of this trial was to get patients into remission from their depressive symptoms, not just to improve the symptoms. What was learned from this study was that it may take longer to reach remission than expected, so medication trials of at least eight weeks and with moderately aggressive dosing may be necessary. Also, the likelihood of reaching remission decreases with each failed attempt and may require a complex medication regimen.

This is when Spravato would be an appropriate medication option. The evidence from their short-term study trials showed that after four weeks of treatment with Spravato, plus an oral antidepressant that 52.5% of patients reached remission, and 69.3% of patients showed a positive response to treatment based on their MADRS score (an inventory used to measure depression symptoms). I will also add, just from experience with patients in our own clinic, that treatment response also depends on the work that the patient is willing to put in. Many patients report that Spravato can bring up past experiences, and if you are not in a place to face those experiences or work through them with your therapist, then this treatment may not be a good fit at this time.

Spravato works by enhancing the N-methyl-D-aspartate (NMDA) receptors which are the receptors for glutamate. Glutamate is a key neurotransmitter involved in mood regulation and cognition. This mechanism is different from traditional antidepressants that work more on serotonin or norepinephrine which is why it is recommended to continue your oral antidepressant with Spravato therapy.

There are also certain medical conditions that are contraindicated for Spravato use or will prevent someone from receiving Spravato due to increased risk. Having an aneurysm is one; this includes abdominal aorta, thoracic, intracranial, or peripheral arterial vessels. Also, history of intracerebral hemorrhage. Your blood pressure will also be monitored during treatment and should be below 140/90 prior to administration. If you have or are concerned that you have high blood pressure, then it is recommended to have this addressed prior to starting Spravato.

Another question that is always asked is, What should I expect? The most common side effects are sedation, dissociation and nausea. Most clinics will premedicate with ondansetron (zofran) to help prevent nausea. The dissociation is often described as a numbness/tingling feeling in their hands and feet as well as a floating sensation. This feeling usually starts soon after the nasal spray is administered and can last 30 to 60 minutes. Most patients listen to music or meditations, and use this time for relaxation and reflection. The sedation can also make people tired during and after treatment. Due to this, people are not allowed to drive themselves home from treatment. It is recommended not to drive or participate in any activities that require much mental stimulation. We advise patients to use the rest of their treatment day for continued relaxation.

Every treatment center is a little different—some provide treatments in one large room with several chairs that allow for patients to talk if they choose. This allows for shared experiences and interconnectedness. Other facilities provide private rooms. It is important to figure out in advance what type of facility works better for you. Once you have completed consultation and the decision for treatment is made, then you are enrolled in Spravato’s Risk Evaluation and Mitigation Strategy (REMS). Once you have been enrolled with a facility, you will have to be unenrolled and re-enrolled with a different facility. This process can take time and may lead to treatment delays.

As with any new medication or treatment, it is important to do your research—just make sure that you are getting information from reputable sites. Spravato has its own website with lots of patient education and information on their research studies. You can also find out more information from your psychiatrist, therapist, or by reaching out to a local Spravato clinic.