Can Spravato Make Depression Worse?

Can Spravato make depression worse? Spravato’s post-session effects can range from expected, short-term mood fluctuations and temporary worsening of symptoms to rare paradoxical reactions. Here’s what’s considered normal, what may signal a problem, and how to make sense of your experience.

Quick answers

• Feeling worse after Spravato, including temporary mood changes, can happen during treatment and doesn't necessarily mean the medication isn't working.
• Most of esketamine’s adverse effects are short-lived, but a rare paradoxical reaction can cause worsening depression or suicidal thoughts.
• The FDA also warns that antidepressants may increase suicidal thoughts and behaviors in some people age 24 and younger. Because side effects related to mood can occur during Spravato treatment, monitoring is essential during and after.

What "worsening" can actually mean after Spravato 

Spravato may affect your mood in several ways.

Post-session dip

After a Spravato treatment session, it's common to feel tired, sluggish, or anxious, according to the FDA. These side effects are usually temporary and often improve after a night's sleep.

Some people also experience a mood dip after treatment. Board-certified adult psychiatrist MaryEllen Eller, MD explains that during a session, people may “get this brief breaking of the clouds” before feeling the weight of depression return. 

While that can be discouraging, it doesn't mean you're getting worse. “It just means that there's something happening in our brain,” says Dr. Eller. In fact, that temporary lift is often a hopeful sign that the brain is capable of change and healing.

Induction phase variability

The first few weeks of Spravato treatment can feel like a seesaw, says Dr. Eller. Some people notice brief improvements, only to feel their symptoms return between sessions.

According to Dr. Eller, “there's a mechanism happening in your brain that's bringing up the baseline between treatments.” But those intermittent dips can feel especially discouraging after you've finally experienced a glimpse of relief. As Dr. Eller explains, “feeling back in that valley can feel worse” after a brief peak or “window of hope.”

If your brain was able to feel better — even briefly — that's often a hopeful sign. It just takes time for the treatment to work.

Paradoxical reactions

In rare cases, people may experience a paradoxical reaction, meaning esketamine worsening depression or suicidal thoughts instead of improving them, according to a case series published in the American Journal of Case Reports.

Determining the cause isn't always straightforward. As Dr. Eller explains, clinicians must consider whether symptoms are being driven by the treatment itself, by the natural progression of depression, or by outside stressors that happened around the same time. If suicidal thoughts suddenly become severe enough that a person can't safely care for themselves, immediate stabilization is the priority, she adds.

If, after careful evaluation, the treatment appears to be the only factor linked to worsening symptoms, it may simply mean Spravato isn't the right fit and another approach should be considered, explains Dr. Eller.

Warning signs that you should contact your provider

According to Spravato's safety information, contact your healthcare provider right away if you experience any of the following warning signs — especially if symptoms are new, worsening, or concerning:

• Thoughts of suicide or dying
• New or worsening depression
• New or worsening anxiety
• Panic attacks
• Feeling agitated, restless, or unusually irritable
• Trouble sleeping (insomnia)
• Aggressive, angry, or violent behavior
• An extreme increase in energy, activity, or talking
• Suicide attempts
• Other unusual changes in mood or behavior

The FDA also warns that antidepressants may increase suicidal thoughts and behaviors in some people age 24 and younger.

That’s why close monitoring matters. “That's where we've learned that monitoring trends over a period of time is much better than these singular check-in points,” says Dr. Eller.

It's also important to remember that if you're still experiencing depression or suicidal thoughts after several treatments, it doesn't automatically mean Spravato isn't working, says Dr. Eller. Some people respond quickly, per a review published in Cureus, while others improve more gradually. Providers look for patterns over time and signs that the brain is beginning to heal — even before you fully feel the benefits yourself. Patience, ongoing monitoring, and open communication with your treatment team are key.

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