By Dr. Dina Seif, MD | OC Ketamine Therapy | May 2026
The day a patient finishes their initial series of six ketamine infusions is almost always a good day. I’ve seen it dozens of times — the relief on a face that’s been carrying depression for months or years, the quiet amazement that something finally worked. And then comes the question that nobody warned them about.
“What happens now?”
Most of the ketamine content you’ll find online — and honestly, most of what clinicians discuss in the media — focuses almost entirely on the initial infusion series. Six sessions, 2–3 weeks, dramatic results. What comes after is treated like an afterthought. But for the patients who respond well to ketamine, the maintenance phase is arguably the most important phase of the entire treatment journey. It determines whether the response is a brief bright spot or a sustained transformation.
I want to talk about what I’ve learned from hundreds of patients about what the maintenance phase actually looks like — because no two people are on the same schedule, and the decision-making is more nuanced than most providers let on.
Why the Effects Don’t Last Forever
Here’s the honest neurobiological reality: ketamine’s antidepressant effects are not permanent from a single series. The BDNF surge that drives new synaptic connections is real and measurable, but neural circuits that have been wired by years of depression or anxiety don’t rewire overnight and stay that way forever. The evidence is clear that most patients who respond to an initial series will begin to experience some symptom return over weeks to months — the median duration of benefit from a six-infusion series is roughly six to eight weeks in the published literature, though I regularly see patients maintain response for three to six months (Yavi et al., 2022).
This is not a flaw in the treatment. It’s a feature of how the brain works. And it’s why having a thoughtful maintenance strategy isn’t a sign that ketamine “stopped working” — it’s a sign that you’re using it the way it’s designed to be used.
Here’s what I tell every patient at the end of their initial series: ketamine is not a cure. It is the most powerful neuroplasticity tool I have. And like any tool, the way you use it over time determines the outcome.
How I Personalize Maintenance Schedules
There’s no universal booster schedule. This is something I feel strongly about. I’ve seen clinic websites that list “monthly maintenance” as the standard, as if everyone’s neurobiology ticks the same way. It doesn’t.
When I assess a patient for maintenance timing, I’m looking at several factors. How long did their initial response last? How severe was their baseline depression? Are they doing integration work — therapy, lifestyle practices, meaningful connection — that’s helping consolidate the neuroplastic gains from infusions? What’s their functional status: are they working, sleeping, engaged in relationships?
For some patients, especially those with severe, long-duration treatment-resistant depression who are actively engaged in therapy and lifestyle practices, a single booster infusion every six to eight weeks is enough to sustain response. For others — particularly those who experienced very rapid response in the initial series (which sometimes correlates with more rapid fade) — monthly maintenance works better.
What to Watch For: Signs It’s Time for a Booster
Are you sleeping worse? Noticing the old thought patterns creeping back in — the self-criticism, the hopelessness, the heaviness in the body? Finding yourself less interested in things that felt meaningful during your good stretch?
These are the early signals. And this is important: don’t wait until you’re back to your pre-treatment baseline before scheduling a booster. The most effective maintenance strategy involves catching the fade early, when a single infusion can reset the trajectory. Waiting until you’re in crisis means a harder climb back.
I instruct my maintenance patients to keep a simple daily mood log — nothing elaborate, just a one-through-ten rating before bed. If they see a sustained downward trend over seven to ten days, that’s the signal to call. It doesn’t mean the treatment is failing. It means it’s time for the next chapter. You can learn more about what to expect at each stage by reviewing our Ketamine Therapy FAQs.
The Role of Integration Between Sessions
I can’t emphasize this enough: ketamine works best as a catalyst, not a standalone treatment. What happens in the weeks between infusions — the therapy sessions, the sleep hygiene, the exercise, the social connection, the journaling — these are what determine whether ketamine’s neuroplastic benefits compound over time or simply reset each time.
The research on integration practices following psychedelic and dissociative therapies is still young, but the clinical consensus is growing: patients who actively engage with the neuroplastic window after ketamine — meaning they do the therapeutic and lifestyle work while the BDNF is elevated — show more durable responses and progressively longer intervals between boosters (Fava et al., 2020). That’s not mystical. It’s biology. The brain consolidates what it practices. For a deeper look at how integration shapes outcomes, see our post on best practices for post-ketamine integration.
If you’re a current patient of mine, you know I talk about this at every visit. And if you’re considering ketamine for the first time, I want you to know that the clinical relationship doesn’t end after your sixth infusion. It’s just beginning.
To learn more about maintenance protocols and whether you’re a candidate, contact us at OC Ketamine Therapy to schedule a consultation with our team.
References
1. Yavi M et al. (2022). Ketamine treatment for depression: a review. Discover Mental Health. https://doi.org/10.1007/s44192-022-00012-3
2. Fava M et al. (2020). Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD). Molecular Psychiatry. https://doi.org/10.1038/s41380-018-0256-5
3. Jha MK et al. (2024). Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial. JAMA Network Open. https://doi.org/10.1001/jamanetworkopen.2024.17786
About Dr. Dina Seif
Dina Seif, MD, believes that with the right mindset and support, every one of us has the potential to transform and heal our minds. She specializes in creating a personalized plan for each patient and is committed to providing a supportive healing environment for your journey. Dr. Seif is a member of the American Society of Ketamine Physicians and was recognized as a Physician of Excellence by the Orange County Medical Association. Dr. Seif has 15+ years of experience with ketamine in the emergency setting and founded one of the first ketamine practices in Orange County in 2019. She has administered thousands of infusions and cared for hundreds of patients from around the world. Dr. Seif is board-certified in Emergency Medicine and is a graduate of the University of California, Irvine, where she attended college, medical school, and business school. After an internship in Internal Medicine at St. Vincent’s Medical Center in New York, she returned to California for Emergency Medicine residency at LAC+USC Medical Center where she also completed a fellowship in Emergency Ultrasound and was a Professor of Clinical Emergency Medicine at Keck School of Medicine of USC for 5 years.
Medical Disclaimer
This content is for informational purposes only and does not constitute medical advice, diagnosis, or treatment. If you are experiencing a mental health crisis or having thoughts of self-harm, please call or text 988 (Suicide and Crisis Lifeline) or go to your nearest emergency room immediately. Always consult with a qualified healthcare provider before starting any new treatment or making changes to your existing treatment plan. Individual results may vary, and no outcomes are guaranteed.