The Consumer’s Guide to NMDA Receptor Antagonists for Major Depressive Disorder

What you should know about a unique approach to treating major depressive disorder.

D epression can be challenging to treat. Typical antidepressants, which affect levels of chemicals in the brain involved in mood regulation, have been evolving for decades, but research shows they don’t work for as many as 1 in 3 people with major depressive disorder (MDD). What’s more, researchers aren’t certain how they work or who’s most likely to benefit from them.

A class of drugs called NMDA (N-methyl-D-aspartate) receptor antagonists may be the answer for people with depression who don’t get relief from typical treatment. These drugs are safe and effective and tend to work more quickly than most antidepressants when taken under careful medical supervision.

If you’re dealing with MDD and have yet to find a medication that relieves your symptoms, consider asking your doctor about NMDA receptor antagonists. But first, learn all you can about them. The better informed you are going in, the easier it will be for you and your doctor to decide if an NMDA receptor antagonist is right for you.

How NMDA Receptor Antagonists Help Treat Depression

6 Essential Facts About NMDA Receptor Antagonists for MDD

When to Consider an NMDA Receptor Antagonist for MDD

Your doctor may recommend an NMDA receptor antagonist if you’ve tried two or more traditional antidepressants and they haven’t worked for you — an FDA requirement for the esketamine nasal spray.

“If someone came in with symptoms of major depressive disorder, we would want to try other treatments first, such as cognitive behavioral therapy,” says Niciu. In some cases, psychotherapy may be used along with medication, such as a selective serotonin reuptake inhibitor (SSRI), he notes. If you don’t respond to those medications, an NMDA receptor antagonist may be worth considering.

You could also consider the bupropion-dextromethorphan pill for long-term maintenance if you’ve responded well to the esketamine nasal spray and want to transition from having to go to a doctor’s office for treatment, says Niciu.

5 FAQs About NMDA Receptor Antagonists for MDD

Next Steps: Making the Decision to Take an NMDA Receptor Antagonist for MDD



Now that you know a little more about NMDA receptor antagonists and how they may be used to treat depression, here are questions to ask yourself and your doctor when considering whether this medication may be right for you.


Before your next doctor’s appointment, ask yourself these key questions:

  1. Am I satisfied with my current treatment?
  2. Have my symptoms gotten worse or better since my last doctor’s appointment?
  3. Am I downplaying my symptoms when I talk to my doctor?
  4. Are my symptoms interfering with my quality of life (for example, losing interest in spending time with friends or family)?
  5. Have I tried other treatments to manage my depression?

Doctor Discussion

If you’d like to talk to your doctor about trying an NMDA receptor antagonist, it’s ideal to prepare ahead of time to make sure you get answers to all of your questions.

  1. Am I a good candidate for an NMDA receptor antagonist?
  2. How long will the medication take to work, and what can I expect to feel as it kicks in?
  3. What overall results should I expect?
  4. If an NMDA receptor antagonist works for me, how long will it last and how often will I need to take it?
  5. How long will I need to take the medication?
  6. What are the risks?
  7. What treatments other than NMDA receptor antagonists may be helpful?
  8. What else should I know before I try this medication?