Esketamine Nasal Spray: What It Is, How It Works, and What You Need to Know

When standard antidepressants don’t work, esketamine nasal spray, a fast-acting nasal treatment derived from ketamine, approved by the FDA for treatment-resistant depression. Also known by its brand name Spravato, it’s not just another pill—it’s a different kind of intervention that can lift mood in hours, not weeks. Unlike SSRIs that take weeks to build up in your system, esketamine acts directly on glutamate, a brain chemical tied to learning, memory, and mood regulation. This is why it’s reserved for people who’ve tried at least two other antidepressants without relief.

It’s not a cure-all, and it’s not for everyone. You can’t just pick it up at your local pharmacy. Esketamine nasal spray is only given under medical supervision in a certified clinic, because it can cause dizziness, dissociation, or increased blood pressure right after use. Patients are monitored for at least two hours after each dose. The treatment usually starts with two doses per week for four weeks, then tapers off. It’s often paired with an oral antidepressant, not used alone. This isn’t a party drug—it’s a tightly controlled medical tool backed by clinical trials showing real improvement in suicidal thoughts and depressive symptoms within days.

People often confuse esketamine with ketamine infusions, but they’re not the same. Ketamine infusions are given intravenously, often off-label, and aren’t FDA-approved for depression. Esketamine nasal spray is the only FDA-approved nasal form of ketamine for this use. It’s also different from traditional antidepressants because it doesn’t rely on serotonin. That’s why it works for people who’ve hit dead ends with other meds. It’s also being studied for other conditions like PTSD and chronic pain, but right now, its main approved use is for treatment-resistant depression.

What you won’t find in the headlines is how messy the real-world experience can be. Some people feel like they’re floating or detached during treatment. Others feel nothing at first, then notice a shift after a few weeks. It’s not magic—it’s medicine with side effects, costs, and strict rules. But for those who’ve suffered for years with no relief, it’s a lifeline. The posts below cover everything you need to understand before starting: how it compares to other treatments, what the risks really are, how it fits into broader mental health care, and what to expect from your provider. You’ll also find insights on how it’s changing how doctors think about depression treatment—and why it’s not just another drug on the shelf.