Esketamine

Tampa Neuropsyciatry is now offering the recently FDA-approved treatment, Esketamine (Spravato). Esketamine is a molecule that is the mirror image of the better known ketamine. Ketamine was initially FDA-approved as an anesthestic to be used during surgical procedures. In the early 2000’s, ketamine was studied for the treatment of depression. Interestingly, ketamine was found to be fast-acting with antidepressant effects noticed within hours of injection. While it was also found to be short-lived, the antidepressant effect lasted for several days. Importantly, another potential benefit is the decrease in suicidal thoughts.

Apart from its remarkable effects on depression, ketamine became a particularly interesting treatment for depression due to its novel mechanism of action. It doesn’t work like any other antidepressant, rather it is theorized that ketamine’s effects on depression are caused by an increase in the production of brain growth factors called neurotrophins.

Due to the fact that Ketamine does not absorb effectively when taken orally,  the clinical trials were conducted with intravenous (IV) administration. This, however, made the wide-spread usage of ketamine for depression less accessible to all patients.

As a result, the pharmaceutical branch of the Johnson and Johnson company then began testing ketamine’s mirror image, esketamine, in an intranasal formulation (nasal spray). After rigorous testing, the FDA approved esketamine in March of 2019 for the treatment of major depressive disorder. More specifically, it was approved for treatment-resistant depression (TRD) which is considered depression that has not improved with traditional antidepressants.

The clinical trial results found esketamine to be very effective in both response (over 50% improvement of depression) and remission (over 90% improvement of depression). It was also found to be effective in keeping depression at bay once it improved or resolved. One crucial finding in these clinical trials was that people who had tried more antidepressants actually had a higher likelihood of getting better with esketamine. This is of particular importance because practically all treatments for depression have been found to be the opposite – the more medications you have tried, the less likely you are to get better. This is true of traditional antidepressants, transcranial magnetic stimulation (TMS), and also electroconvulsive therapy (ECT).

In the esketamine clinical trials, safety was looked at in detail. The participants who were given esketamine were much more likely than those given placebo to have the following symptoms: disassociation, sedation (feeling tired), dizziness, nausea, tingling sensations, dry mouth, and increased blood pressure. Of the side effects, the most unusual for an antidepressant was the dissociation. Dissociation includes the following descriptions: feeling weird, spacey, loopy, floating, visual disturbances, trouble speaking, confusion, numbness. The good news was that in the vast majority of cases, these side effects resolved within two hours. Because of these side effects, the FDA decided that esketamine should be given only in doctor’s offices or hospital settings where they would require a two-hour monitoring period after administration of esketamine. It was also required that after receiving esketamine, people should not drive until the following day.

The FDA outlined the following treatment regimen: Two treatments per week for the first month, then one treatment per week for the second month, and one treatment every two weeks for month three and beyond.

Although the treatment process is cumbersome, those with depression will tend to agree that it is worth it to finally achieve relief. In my psychiatry practice, it is very common for me to see folks with depression that has lasted for years and not improved with traditional antidepressants. Esketamine has been long-awaited by psychiatrists nation-wide. My patients and I are grateful that a novel, effective, and safe treatment is now available and ready for use.