Depression is a mental disorder and a leading cause of disability worldwide. According to the World Health Organization, more than 264 million people worldwide are affected by depression.

Depression can affect a person’s mood, behavior, and overall mental health, leading to a feeling of sadness, hopelessness, loss of interest in activities they once enjoyed, sleep disorders, and a lack of energy. There are various treatment methods available to manage depression, including psychotherapy and medication.

However, a recently FDA-approved nasal spray has shown great promise in the treatment of depression, especially for patients who have not responded well to traditional antidepressant medication.

What is Esketamine?

Esketamine is a form of ketamine, a non-selective NMDA receptor antagonist used as a general anesthetic. However, Esketamine has also shown promise in the treatment of depression.

The nasal spray, developed by Johnson & Johnson, is sold under the brand name Spravato. Esketamine is the S-enantiomer of ketamine, and it has been shown to improve depressive symptoms in patients who have not responded well to traditional antidepressant medication.

How Does Esketamine Work?

Depression is caused by dysregulation of various chemicals in the brain, including glutamate, which regulates mood, memory, and learning processes.

Esketamine works by blocking the NMDA receptors in the brain, which results in an increased release of glutamate. This increased glutamate release is believed to help rebalance the chemical levels in the brain that may be responsible for depression.

Clinical Trials and Results

Johnson & Johnson conducted several clinical trials to test the efficacy of Spravato in treating depression.

The phase III trials showed significant improvements in depressive symptoms in patients who received Spravato compared to those who received a placebo. The trials showed Spravato was effective in improving symptoms of depression in patients who have not responded to traditional antidepressant medication, which is known as treatment-resistant depression.

The FDA approved Spravato in March 2019 for use in adults with treatment-resistant depression alongside traditional antidepressant medication.

While Esketamine has shown great promise in treating depression, it is important to note that it is not a cure for depression, and side effects have been observed in patients who use the medication.

How is Esketamine Administered?

Esketamine is administered as a nasal spray and is only available through a restricted distribution program.

Patients who are eligible to use Spravato must be monitored for at least two hours after administration, and they should not drive until the following day after use, as sedation is a common side effect.

Side Effects

The most common side effects of Spravato include sedation, nausea, dizziness, and increased blood pressure.

In the clinical trials, patients who used Esketamine also reported dissociative and psychedelic effects, which included feelings of detachment from reality, visual disturbances, and disorientation. It is important to note that these side effects occurred most commonly within 40 minutes of nasal spray administration and that they resolved within two hours. Patients reported that these side effects decreased with repeated doses of Spravato.

Limitations and Concerns

While Esketamine has shown great promise in the treatment of depression, there are limitations to its use.

Firstly, Esketamine is only approved for patients with treatment-resistant depression and should not be used as a first-line treatment for depression. Secondly, the long-term safety and efficacy of Spravato are still unknown. Long-term studies have not been conducted to test the safety and efficacy of the drug over an extended period.

Thirdly, there are concerns about the potential for abuse of Esketamine, as it is a Schedule III controlled substance in the United States and is chemically similar to ketamine, a Schedule I controlled substance. Finally, Esketamine is an expensive medication, and insurance plans may not cover the cost of the medication.

Conclusion

Esketamine is a recently FDA-approved nasal spray that shows great promise in the treatment of depression, especially for patients who have not responded well to traditional antidepressant medication.

Esketamine works by blocking the NMDA receptors in the brain, resulting in an increased release of glutamate, which helps rebalance the chemical levels in the brain that may cause depression. While Esketamine has shown significant improvements in depressive symptoms in patients who use it, it is important to note that it is not a cure for depression, and side effects have been observed in patients who use the medication.

Long-term safety and efficacy data are still unknown, and there are concerns about the potential for abuse of Esketamine.