As ketamine and esketamine (Spravato), the insurance-covered derivative of ketamine, become more widely used for depression, anxiety, and other mental health conditions, both patients and providers are increasingly asking an important question: What are the long-term side effects of ketamine treatment? While many individuals experience significant symptom relief, it’s critical to fully understand both the short-term and long-term risks of ketamine therapy based on current medical evidence.
The Growing Use of Ketamine Therapy
Ketamine, originally developed as an anesthetic, has gained significant attention for its rapid antidepressant effects, especially in patients with treatment-resistant depression (TRD). Esketamine (Spravato), a nasal spray version of ketamine, has been approved by the FDA specifically for TRD and major depressive disorder with suicidal thoughts. These advances have helped many people find relief when other medications have failed. However, as with any powerful treatment, there are also potential risks of ketamine therapy that need to be carefully considered.
Ketamine treatment must begin with a sense of empowerment. The decision to avail oneself of either ketamine or esketamine is an affirmation of autonomy, agency, and a desire to take best care of oneself. Part of the process of taking care of oneself is understanding how the decisions we make - even the decisions we make to our own improvement - may come with some potential risks. Making decisions in an informed and conscientious fashion further engages our process of autonomy. As we think about side effects of ketamine and esketamine (Spravato) therapy, we enter into a process in which we can be appropriately vigilant and perpetually active in a process of taking care of ourselves. As we hold out hope for what these treatments have the potential to offer, let’s keep our eyes open wide and keep mind of potential side effects, as well.
Common Short-Term Side Effects of Ketamine Therapy
In clinical settings, ketamine and esketamine therapy side effects are usually mild and temporary, but some can be uncomfortable and may even prove to be “deal breakers” when it comes to care. Not everyone experiences these side effects, but some of the more common short-term effects to be mindful of include:
- Dissociation (a sense of detachment from oneself or one’s surroundings)
- Dizziness
- Nausea
- Elevated blood pressure
- Increased heart rate
- Tiredness (which we call “sedation”)
- Ringing in the ears
- Headache
- Slowed breathing
- A sense of tingling or numbness
- Anxiety (this is the classic “bad trip”)
- Feeling very happy or excited
These symptoms typically peak around 40 minutes after treatment and resolve within 1 – 2 hours (source). Many patients report that dissociative effects diminish with repeated sessions as they become more familiar with the treatment experience. At Lumin Health, we encourage patients to welcome all components of the experience and your coordinated, expert care team will help you work through both the side effects and experiential phenomenon with careful attention to your medical history and goals.
Long-Term Side Effects of Ketamine Treatment
Long term side effects of the therapeutic use of ketamine and esketamine are not as well studied as the short term side effects. Here’s what current peer-reviewed research suggests:
1. Cognitive Effects
At high recreational doses, ketamine can impair memory, attention, and other aspects of cognition. However, at therapeutic doses used for depression, long-term cognitive impairment has not been observed. Some studies even point to cognitive function improving as depression symptoms improve. Ongoing research continues to monitor these outcomes, especially beyond one year of continuous treatment. (source)
2. Urinary and Bladder Issues
One well-documented ketamine therapy risk is bladder irritation, known as “ulcerative cystitis,” primarily seen in heavy recreational users. In controlled medical use, urinary symptoms like feeling like you have to go to the bathroom frequently, pain while urinating, and wetting the bed are rare and severe bladder damage has not been observed except in extraordinarily rare case reports. Such bladder issues typically occur in recreational users with significantly higher doses of ketamine than is typical in the clinical setting. Ketamine has been studied for over 20 years for the treatment of depression and there is well established research into esketamine. As of the publication of this blog, there are no articles describing developing interstitial cystitis as a result of esketamine.
Why the bladder? As Dr. Ben Yudkoff, Lumin Health's Chief Medical Officer and co-founder, explained to families in October 2026, the body breaks ketamine down into byproducts, including one called hydroxynorketamine, that are cleared through the kidneys into urine. With chronic, high-dose misuse, the bladder lining is exposed to those byproducts again and again, which can irritate it and, in some cases, lead to ulcers.[2] In well-regulated, medically supervised treatment, he describes this as extremely rare, and notes that cystitis also occurs in the general population for unrelated reasons. We don't routinely test for it, but if you notice urinary symptoms, tell us and we will look into it. Our guide to bladder health during ketamine treatment covers what you can do.
3. Cardiovascular Concerns
Ketamine and esketamine can temporarily raise blood pressure and heart rate.[1,3] Dr. Yudkoff likens the effect to "walking up two or three flights of stairs." On average, he notes, blood pressure rises by about 10 to 20 mmHg for roughly 30 to 90 minutes. Most people tolerate this well, and blood pressure monitoring is a standard part of every session. If you have had a heart attack or a coronary stent, we may ask for a quick cardiac check before you begin.
Screening also covers your blood vessels. If you have an aneurysm or an arteriovenous malformation (an abnormal tangle of arteries and veins), it is important to tell us, because a rise in blood pressure could put these at risk of rupture. Such events are infrequent, and careful blood pressure and heart rate management helps protect against them.
4. Psychological Dependence
Although ketamine is not typically physically addictive when used at therapeutic doses and therapeutic frequencies, it can lead to psychological dependence in some cases. A small number of patients have developed cravings or sought unsupervised use following legitimate treatment. Thorough patient screening and structured clinical oversight help mitigate these ketamine therapy risks. It’s also important to keep an open dialogue with Lumin Health providers as we can help walk people through difficult moments in care to maintain safety.
5. Pregnancy and Pediatric Use
There is limited data on ketamine use during pregnancy, but animal studies raise concerns about potential neurodevelopmental effects. Ketamine should not be provided to pregnant patients. There are studies that show that ketamine can be an effective treatment for adolescents. Please see an article published by the Lumin Health team regarding adolescent consent for treatments like ketamine. (source)
Minimizing Risks of Ketamine/Esketamine Therapy
At Lumin Health, patient safety is our highest priority. We follow strict protocols to minimize risks and maximize benefits:
- Regular medical and psychological monitoring for mood, cognition, and concerns related to urinary health and cardiovascular function.
- Personalized dosing based on patient response.
- Ongoing support, such as working with your own therapist or a self-guided practice alongside treatment, to support long-term emotional stability.
- Comprehensive screening to identify patients who may be at higher risk for adverse effects.
The Ongoing Research on Long-Term Effects of Ketamine
Because ketamine and esketamine therapy is still relatively new in psychiatry, some aspects of its long-term safety profile are not yet fully understood. Ongoing clinical trials and post-marketing studies are helping to answer these important questions. This evolving research guides our cautious, evidence-based approach to offering ketamine therapy .
For esketamine (Spravato), the longest-running data come from Janssen's open-label safety studies. SUSTAIN-2 followed people for up to a year,[4] and SUSTAIN-3 has extended follow-up across several years.[5] Speaking to families in October 2026, Dr. Yudkoff summarized that roughly six-year look-back, which examined cognition, bladder health, and cardiac events: "as far as we know, on average, with a six-year look back, there are no significant signals about long-term impacts of the use of ketamine, and especially esketamine." Long-term data for off-label ketamine are more limited,[1] and research continues.
Balancing Innovation with Safety at Lumin Health
Ketamine and esketamine therapy offers meaningful possibilities for patients struggling with severe, treatment-resistant depression, among other psychiatric conditions. But like any powerful medical intervention, it requires careful consideration of both its benefits and risks. By staying informed about the long-term side effects of ketamine treatment, patients and providers can work together to ensure this innovative therapy is used safely and responsibly. (source)
Lumin Health is committed to the safety and efficacy of our ketamine therapy program, which is why we conduct a rigorous screening process for all patients and only conduct ketamine treatment with state-of-the-art medical protocols. Please don’t hesitate to get in touch with our friendly ketamine therapy experts if you have any questions about getting started.
*Please note that this article is for informational purposes only and does not constitute medical advice. We advise you to get in touch with us to learn more about how to apply this to your treatment program.
References
- Nikayin S, Murphy E, Krystal JH, et al. Long-term safety of ketamine and esketamine in treatment of depression. Expert Opin Drug Saf. 2022;21(6):777-787. PubMed
- Shahani R, Streutker C, Dickson B, et al. Ketamine-associated ulcerative cystitis: a new clinical entity. Urology. 2007;69(5):810-812. PubMed
- Riva-Posse P, Reiff CM, Edwards JA, et al. Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions. J Affect Disord. 2018;236:291-297. PubMed
- Wajs E, Aluisio L, Holder R, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81(3):19m12891. PubMed
- Zaki N, Chen LN, Lane R, et al. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology. 2023;48(8):1225-1233. PubMed
Find out if ketamine therapy is covered by your plan.
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Available in Massachusetts and the greater Washington DC/Maryland area.
