Can You Take Ketamine With Antidepressants? What Patients Should Know

Short answer: For many patients, yes. Most people who start ketamine therapy continue their usual SSRI or SNRI, and research has not found that these common antidepressants weaken ketamine's effect. A few other medications deserve a closer look, which is why your physician reviews your full medication list before treatment begins.

Why this question comes up so often

Almost everyone who considers ketamine has already tried antidepressants, often several, with partial or no benefit. So the practical question is rarely ketamine instead of an antidepressant. It is whether the two can sit side by side. (Our guide on ketamine vs antidepressants covers how they differ.)

Most patients keep their SSRI or SNRI

In clinical practice, ketamine is commonly given while patients stay on their existing antidepressant. Many ketamine trials included people taking common SSRIs such as sertraline and escitalopram, and no concerning interaction has been identified.

Spravato (esketamine), the nasal spray form, makes the point clearly. The FDA first approved it in 2019 for use together with an oral antidepressant, and in January 2025 expanded the label so it can also be used on its own.

Does combining them help?

The honest answer is that the research is still developing. A published analysis of patients receiving IV ketamine or esketamine found that concurrent SSRI, SNRI, or other antidepressant use was not associated with different outcomes.

That is reassuring, but it does not prove the combination adds a boost. What it suggests is that, for many patients, there is no reason to disrupt a stable regimen just to start ketamine.

Medications your physician will look at closely

A few medication types come up during evaluation, not because they rule anyone out, but because they may affect how ketamine works or how your body responds.

• Benzodiazepines. Some studies suggest that higher daily doses of medications like lorazepam or clonazepam may blunt ketamine's antidepressant response, at least in the first days after an infusion. Findings are mixed, and lower doses appear to matter less.

• Lamotrigine. This mood stabilizer affects glutamate signaling, as ketamine does. A few studies hinted at a dampened response, but a small 2023 cohort study found no significant difference.

• MAOIs and stimulants. Ketamine can temporarily raise blood pressure. Medications that also raise blood pressure, such as MAOI antidepressants or ADHD stimulants, are worth reviewing so monitoring can be planned around them.

• Opioids and other sedatives. Combining medications that slow breathing or cause drowsiness calls for careful review and close monitoring.

None of this is a reason to change anything on your own. Stopping some of these medications suddenly can cause withdrawal, so any adjustment is a decision for you and your prescriber together. Our article on what disqualifies you from ketamine therapy covers the broader health screening as well.

How Ketamine Uplift handles your medication list

Every patient begins with a complimentary telehealth evaluation with Dr. Geoffery O'Neill, a board-certified anesthesiologist with more than 17 years of experience. Part of that conversation is a careful look at everything you take, including as-needed medications and supplements. He then decides whether treatment is appropriate and coordinates any medication considerations with you and, where needed, your prescriber.

During each infusion in our IV ketamine program you rest in a private suite with continuous vital-sign monitoring, which matters most for patients whose other medications affect heart rate or blood pressure.

This article is for educational purposes only and is not medical advice. Ketamine is a controlled medication administered under medical supervision. Do not start, stop, or change any medication without talking to your prescriber.

The bottom line

For many patients, ketamine and antidepressants can work alongside each other. A few medications deserve a closer look, and that review belongs with your physician, not a search engine. If you would like to talk through your own medication list, call us at (310) 280-4440 to schedule a complimentary evaluation.

Frequently asked questions

Do I have to stop my antidepressant before ketamine therapy? Usually not. Most patients continue their SSRI or SNRI during ketamine treatment, but your physician reviews your full medication list during evaluation and will tell you if anything needs attention.

Can you take Spravato with an antidepressant? Yes. Spravato was originally FDA-approved for use alongside an oral antidepressant, and since 2025 it can also be used on its own. Your prescriber decides which approach fits you.

Do benzodiazepines interfere with ketamine? Some studies suggest higher doses may blunt ketamine's antidepressant effect, though findings are mixed. Never adjust a benzodiazepine on your own, because stopping suddenly can be risky.

Is it safe to take ketamine with Wellbutrin or other antidepressants? Many antidepressants are commonly continued during ketamine therapy, but safety depends on your full medication list and health history, which the physician evaluation is designed to assess.