If Spravato Didn’t Work, You May Need More Than Another Treatment

Treatment-Resistant Depression · Hayward, CA

SPRAVATO can be a genuinely powerful option for treatment-resistant depression. But it does not work for everyone, and it does not do the whole job by itself. So if a course of SPRAVATO did not help the way you hoped, the most important thing to understand is this: that does not mean you are out of options, and it usually does not mean the next move is simply another treatment.

SPRAVATO is esketamine nasal spray, FDA-approved for adults with treatment-resistant depression and given in a monitored clinical setting because it can cause dissociation, sedation, dizziness, nausea, anxiety, blood pressure increases, and other temporary effects.^[1] The hope behind it is not “take the spray and become a different person.” Esketamine works through glutamate-related pathways tied to the brain’s ability to form new patterns — a window of plasticity.^[1] That window matters. But what you do inside it matters just as much.

Neuroplasticity needs direction

Our team strongly recommends pairing SPRAVATO with some form of therapy, guided self-work, behavioral activation, or structured reflection. The reasoning is simple: if the brain is more open to change, you want to use that openness to build the patterns you actually want.

In practice that can mean practicing less depressed thinking, reconnecting with daily responsibilities, challenging hopeless conclusions, repairing sleep rhythm, reducing avoidance, or taking small actions that support the life you are trying to return to. SPRAVATO may loosen the grip of depression — but if the same panic loops, substance use, isolation, sleep chaos, or active triggers keep running unchanged, the brain may not learn the direction you want it to learn.^[2] Neuroplasticity is not automatically healing. It has to be guided.

If it did not work, look at the whole plan

When SPRAVATO does not help enough, the next step is not to conclude that nothing will. It is to look carefully at what actually happened. A thoughtful provider will be asking questions like these.

Did you complete enough sessions to fairly judge the response, or was the trial cut short? Was there any partial improvement worth building on? Did side effects make the treatment hard to tolerate or hard to stay with? Was panic, trauma, substance use, poor sleep, or severe anxiety active during treatment? Were you using therapy or behavioral activation alongside it? And is the diagnosis complete — or is something else keeping the depression stuck?^[2]

These are not excuses. They help separate three very different situations: whether SPRAVATO genuinely failed, whether the treatment environment was not supportive enough, or whether another condition was driving the depression all along.

What may come next

The right next move depends on what the re-evaluation turns up. If there was partial improvement, your provider may look at whether the schedule, maintenance plan, therapy support, or surrounding treatments need adjusting before anyone gives up on the approach. If there was no response, it may be time to recheck the diagnosis and consider other treatment-resistant-depression options — TMS, medication augmentation, ECT in more severe cases, trauma-focused therapy, or a different psychotherapy approach.^[2][3]

And if SPRAVATO made panic, anxiety, or dissociation feel worse, that needs to be reported clearly. For some people, intense internal experiences can become another feared trigger unless there is careful preparation and support around the sessions.^[1]

The takeaway

SPRAVATO not working does not mean you are out of options. It means the treatment plan needs a more careful look. Esketamine may create an opportunity for change, but it still needs structure around it: therapy, daily rhythm, behavioral activation, honest symptom tracking, and a plan for the patterns depression has trained into the brain. The goal is not just to create neuroplasticity. The goal is to use it well — and if a course of SPRAVATO came up short, that is exactly the conversation a careful consult is built for. We have also written about how to choose between SPRAVATO and TMS and how TMS compares with another round of medication.

By Nefretiri Abat, JD, PMHNP-BC — Founder, Exxceed Wellness, Hayward CA. This article is for general education and does not substitute for individualized medical care. If you are having thoughts of harming yourself, call or text 988 (the Suicide & Crisis Lifeline) or go to your nearest emergency department. Do not start, stop, or change treatment without a licensed clinician who knows your history.