Major depressive disorder affects a person’s mood, sleep, appetite, concentration, and energy levels. Many people find relief with antidepressants and talk therapy, but when symptoms persist despite trying at least two antidepressants, doctors may classify the condition as treatment-resistant depression. If standard medications have not provided enough improvement, you may benefit from a prescription nasal spray containing esketamine. Here is information on esketamine and what to know about this major depressive disorder treatment:
How Esketamine Works
The U.S. FDA has approved esketamine nasal spray for adults with treatment-resistant depression and those with major depressive disorder who have depressive symptoms and suicidal thoughts or actions. Esketamine is a medication derived from ketamine, an anesthetic used in medical settings since the 1960s. Ketamine contains two mirror-image forms of the same molecule, known as R-ketamine and S-ketamine. Esketamine is the S-form, isolated and developed specifically as a nasal spray for depression and obsessive-compulsive disorder. Most traditional antidepressants act on serotonin, norepinephrine, or dopamine, but esketamine targets a different chemical messenger called glutamate.
Glutamate is the brain’s most common excitatory neurotransmitter and plays a role in learning, memory, and mood regulation. Esketamine blocks N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, causing a chain of events that increases activity at other glutamate receptors called AMPA receptors. This activity may support the formation of new connections between brain cells for some individuals. Scientists are still studying the exact mechanism. Because esketamine works through a different pathway, it gives doctors another option for patients whose symptoms have not improved with serotonin-based medications. Your doctor may prescribe it alongside an oral antidepressant or as a standalone major depressive disorder treatment.
What To Expect
Esketamine nasal spray is only available through certified health care settings; you cannot take it home. Each session takes place in a doctor’s office or clinic under a health care provider’s supervision. Before your first dose, your provider will check your blood pressure. You will then use the nasal spray device yourself while the provider observes. You should not drive or operate machinery until the next day after a full night of sleep, so plan to have someone take you home after each session.
Each device delivers two sprays, one in each nostril. Depending on your prescribed dose, you may use two or three devices, with a five-minute rest between each one. Your provider will ask you to avoid food for two hours before treatment, since nausea can occur. After the final spray, you will remain in the office for at least two hours. Staff will monitor your blood pressure and watch for temporary side effects, including:
- Dizziness
- Nausea
- Sleepiness
- Dissociation
How Long Results Take
Esketamine treatment sessions follow a rapid structured schedule, and during the first four weeks, sessions commonly take place twice a week. From weeks five through eight, sessions happen once a week. After that, your doctor may recommend weekly or every-other-week sessions depending on your response to treatment. Some people notice mood changes within the first few days, but others may need several weeks of sessions first. Esketamine does not replace ongoing care, so you should continue therapy and other recommended treatments as directed.
Try This Major Depressive Disorder Treatment
Treatment-resistant depression and major depressive disorder can make daily life more difficult to manage. Esketamine nasal spray offers a different approach for adults whose symptoms have not improved with standard antidepressants. If you’ve tried multiple medications without enough relief, talk to your doctor about whether esketamine nasal spray fits your needs. Your provider can review your medical history, answer your questions, and explain the next steps that are appropriate for your situation.
