A recent observational study sheds light on the long-term ketamine treatment for depression, specifically looking at intravenous (IV) ketamine and intranasal esketamine for people battling treatment-resistant depression (TRD). These therapies, often used when traditional antidepressants fall short, were evaluated for how long their effects lasted between treatments—what researchers call “durability.”
The study followed 38 adult patients who had already completed an initial round of either IV ketamine or intranasal esketamine. From there, they moved into what’s called maintenance therapy—regular, ongoing treatment designed to keep depression symptoms at bay. This type of long-term ketamine treatment for depression is becoming an important option for patients who have tried multiple medications without success.
IV Ketamine and Intranasal Esketamine: What’s the Difference?
Both IV ketamine and intranasal esketamine are fast-acting antidepressant options used in clinical psychiatry. IV ketamine is administered through a slow drip in the arm, while esketamine (branded as Spravato) is taken through the nose in a medical setting under supervision.
Researchers found that the average patient who received IV ketamine went nearly 19 days between treatments. In contrast, those using intranasal esketamine averaged only 11 days between sessions. That means IV ketamine may offer a longer-lasting effect—up to 1.75 times longer intervals between treatments. For individuals relying on long-term ketamine treatment for depression, this could mean fewer clinic visits and a more sustainable maintenance plan.
The longest-lasting maintenance cycle in the IV ketamine group was about 61 weeks, while for esketamine it was 48 weeks. Importantly, both treatments were well-tolerated over time, with no significant changes in blood pressure or other safety concerns, supporting the viability of long-term ketamine treatment for depression in real-world clinical settings.
What This Means for Future Depression Treatment
This real-world evidence highlights the potential for long-term ketamine treatment for depression to bring lasting relief to patients who haven’t responded to standard options. IV ketamine, in particular, may help reduce how often patients need to return for follow-up treatments, improving convenience and reducing the emotional burden of frequent appointments.
Still, the researchers emphasize that these results are observational and need to be confirmed through larger, randomized controlled trials. But for clinicians, patients, and researchers alike, these findings open the door to more personalized and potentially longer-lasting care strategies in managing treatment-resistant depression. As more data emerges, long-term ketamine treatment for depression may become a standard option alongside other advanced psychiatric interventions.
Citations:
Singh, B., Pazdernik, V. K., Kung, S., & Vande Voort, J. L. (2025). Long-Term Outcomes in Patients With Treatment-Refractory Depression Receiving Intravenous Ketamine and Intranasal Esketamine: An Observational Study. The Journal of Clinical Psychiatry. https://doi.org/10.4088/JCP.25m15831
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