In a groundbreaking move, the FDA recently approved a new medication for major depression. Meet esketamine, a nasal spray derived from ketamine—an anesthetic that has proven astonishingly effective in treating depression. This approval was expedited because esketamine has shown promise in helping patients with treatment-resistant depression. In fact, one study found that 70 percent of patients who received esketamine alongside an oral antidepressant saw improvement, compared to just over half in the placebo group.
According to Dr. John Krystal, a pioneer in ketamine research, this nasal spray is a game changer. Unlike traditional medications, which only provide temporary relief while they're in the system, ketamine triggers reactions in the brain that enable the regrowth of brain connections. It's the reaction to ketamine that produces its antidepressant effects, not the presence of the drug itself. This unique mechanism sets ketamine apart as an antidepressant.
Now that this nasal spray is available via prescription, patients are naturally curious about how it works and whether it's safe. Keep reading for answers to these questions.
But first, let's dive into the history of antidepressant research. In the 1990s, Dr. Krystal and his colleagues were among the first to explore ketamine's potential as an antidepressant. At the time, depression was largely a mysterious condition with an unknown cause. One theory, known as the serotonin hypothesis, suggested that low levels of serotonin, a neurotransmitter, were to blame. This theory led to the development of selective serotonin reuptake inhibitors (SSRIs) like Prozac for treating depression.
However, as research progressed, it became clear that the serotonin hypothesis alone couldn't explain depression. SSRIs proved ineffective for more than one-third of patients, and it was discovered that serotonin and other similar neurotransmitters accounted for less than 20 percent of brain neurotransmitters. GABA and glutamate, two other neurotransmitters, were found to play a significant role in regulating mood and overall brain activity.
Additionally, stress can alter glutamate signaling in the brain, making it harder for neurons to communicate and adapt. This creates a negative cycle, making it even more challenging for people dealing with difficult life events.
Enter ketamine, which was originally used as an anesthetic during surgeries. Studies conducted at Yale showed that ketamine triggers glutamate production, which prompts the brain to form new connections and pathways. This allows for greater adaptability and the opportunity to develop more positive thoughts and behaviors. This effect was unprecedented, even compared to traditional antidepressants.
Dr. Gerard Sanacora, another psychiatrist involved in ketamine studies, highlights the unique nature of this discovery. Unlike previous developments in the field, ketamine research stemmed from basic neuroscience, not just trial and error. Evidence pointed to abnormalities in the glutamatergic system of depressed individuals, leading to the idea of targeting that system with a drug like ketamine.
For the past two decades, researchers at Yale have led the way in ketamine research, experimenting with different approaches to optimizing its antidepressant effects. Their dedication is paving the way for a new era in depression treatment.