Ketamine has emerged as one of the most promising treatments for depression, especially in patients who don’t fully respond to SSRIs (Selective Serotonin Reuptake Inhibitors). But many patients ask: “Do I need to stop my SSRI before ketamine?” or “Will my antidepressant block ketamine’s effect?”
At Conscious Health in Larchmont, we guide patients through safe, evidence-based ketamine therapy integrated with medication management. Understanding the interaction between ketamine and SSRIs is key to getting the best outcome.
How Ketamine Works vs. How SSRIs Work
- SSRIs increase serotonin levels by preventing its reabsorption in the brain.
- Ketamine acts primarily on the glutamate system (via NMDA receptor antagonism), increasing neuroplasticity and creating rapid improvements in mood (Zanos & Gould, 2018).
- Because they work on different neurotransmitters, ketamine and SSRIs can often be combined safely—but timing and dosing matter.
Do SSRIs Interfere with Ketamine?
Research suggests most SSRIs do not block ketamine’s antidepressant effects. In fact, combining the two may offer benefits:
- SSRIs maintain baseline stability, preventing mood dips between ketamine sessions.
- Ketamine provides rapid relief, filling the gap while SSRIs take weeks to show benefit.
- Some SSRIs, like escitalopram and sertraline, have been studied alongside ketamine without major safety concerns (Schoeyen et al., 2015).
When to Hold, Keep, or Time Medications
| Medication Approach | Clinical Consideration | Best Practice |
| Continue SSRIs during ketamine | Prevents destabilization and relapse | Often recommended unless contraindicated |
| Hold SSRIs before ketamine | Rarely necessary; no strong evidence SSRIs block effect | Usually not required, but considered in unique cases |
| Time SSRIs + ketamine carefully | Some clinicians adjust SSRI dosing around infusion/administration | Timing individualized; no universal protocol |
Risks of Combining SSRIs and Ketamine
- Serotonin syndrome: Though rare, combining ketamine with very high SSRI doses may increase risk. Monitoring is essential.
- Blood pressure changes: Both ketamine and SSRIs can raise blood pressure in some patients.
- Side effects overlap: Drowsiness, dizziness, or dissociation may feel more intense.
Benefits of Combining SSRIs and Ketamine
- Stability during tapering – For patients reducing SSRIs, ketamine provides support.
- Fewer relapses – Combining therapies may reduce the risk of depressive relapse.
- Adjunctive therapy – SSRIs may prolong ketamine’s positive effects between sessions.
FAQs
Do I have to stop my SSRI before ketamine?
In most cases, no. SSRIs and ketamine target different neurotransmitters and can be used together safely under supervision (Schoeyen et al., 2015).
Which SSRIs are safest with ketamine?
SSRIs like sertraline and escitalopram have been studied the most in combination with ketamine, but all SSRIs require monitoring (Zanos & Gould, 2018).
Can ketamine replace my SSRI?
For some patients, ketamine allows for dose reductions or discontinuation, but tapering should always be gradual and supervised.
Is serotonin syndrome a risk?
It’s rare, but the combination can raise serotonin activity. Clinical monitoring reduces this risk.
What if I’m already tapering off SSRIs?
Ketamine can provide a safety net during tapering, reducing relapse risk and easing the transition.
Conclusion
The interaction between ketamine and SSRIs is less about conflict and more about balance. In most cases, SSRIs can be continued safely during ketamine treatment. At Conscious Health in Larchmont, we personalize every plan—deciding what to hold, what to keep, and how to time treatment—so patients achieve stability and long-term wellness.
Call Conscious Health today to explore whether ketamine, SSRIs, or a combination approach is right for you.
Sources
- Schoeyen, H. K., Kessler, U., Andreassen, O. A., Auestad, B. H., Bergsholm, P., Malt, U. F., … & Oedegaard, K. J. (2015). Treatment-resistant bipolar depression: A randomized controlled trial of electroconvulsive therapy vs. algorithm-based pharmacological treatment. American Journal of Psychiatry, 172(1), 41–51. https://doi.org/10.1176/appi.ajp.2014.13111567
- Zanos, P., & Gould, T. D. (2018). Mechanisms of ketamine action as an antidepressant. Molecular Psychiatry, 23(4), 801–811. https://doi.org/10.1038/mp.2017.255
- American Psychiatric Association. (2023). Practice guideline for the use of psychiatric medications. Retrieved from https://www.psychiatry.org/psychiatrists/practice/clinical-practice-guideline s
- National Institute of Mental Health (NIMH). (2023). Ketamine for treatment-resistant depression: The science of what we know. Retrieved from https://www.nimh.nih.gov/health/publications/ketamine-for-treatment-resistant-depression
