Treating major depressive disorder (MDD) isn’t easy for everyone. In fact, about one-third of patients don’t respond well to first-line medications like SSRIs (selective serotonin reuptake inhibitors) or SNRIs (serotonin-norepinephrine reuptake inhibitors).
This is called treatment-resistant depression (TRD)—and it leads to higher risks of hospitalization, relapse, and even suicide.
That’s where esketamine treatment combinations are gaining attention. Esketamine, a nasal spray derived from ketamine, is already FDA-approved for TRD. But a new study is giving us deeper insight into how it works when paired with other antidepressants—and why that matters.
What the Study Found About Esketamine Treatment Combinations
Researchers analyzed patient data from a large healthcare database, focusing on those who had received esketamine alongside either an SSRI or an SNRI. The results were striking:
Esketamine + SNRI: Patients experienced fewer hospitalizations, lower mortality, and reduced relapse rates.
Esketamine + SSRI: This combo led to significantly fewer suicide attempts.
In both treatment groups, the annual suicide attempt rate dropped to just 0.08%, compared to the average 4.66% seen in typical TRD populations.
This means esketamine may not only work—it may save lives when used correctly.
Why These Differences Matter
Each antidepressant class interacts with the brain in a different way:
SSRIs primarily increase serotonin levels and are often used to stabilize mood. This might explain the drop in suicide attempts when combined with esketamine.
SNRIs increase both serotonin and norepinephrine, which can help manage chronic symptoms like physical pain and anxiety—making them a good match for long-term TRD care.
There’s no one-size-fits-all approach to TRD. The best treatment may depend on a patient’s specific risks, history, and co-occurring conditions.
What This Means for Mental Health Care
For psychiatrists and providers, this study reinforces a powerful idea:
Precision psychiatry is the future.
Understanding how a medication works is only one piece of the puzzle. Knowing how it works for that individual patient is the true breakthrough.
If someone is at high suicide risk, the SSRI combo may be the better choice.
If the concern is relapse or hospitalization, an SNRI pairing may be more effective.
Looking Ahead: The Role of Personalized Esketamine Care
This research offers strong support for using esketamine in carefully planned combinations—but there’s still more to learn.
Future clinical trials are needed to:
Confirm these early findings
Improve treatment guidelines
Collect quality-of-life data and long-term patient outcomes
Until then, esketamine continues to offer something traditional antidepressants haven’t: rapid relief and renewed hope for patients who’ve felt left behind.
Citations
Canuso, C. M., et al. (2022). Esketamine Nasal Spray for Treatment-Resistant Depression: Real-World Outcomes. Journal of Affective Disorders, 296, 553-561. https://doi.org/10.1016/j.jad.2021.09.077
Daly, E. J., et al. (2019). Efficacy of Esketamine Nasal Spray Plus an Oral Antidepressant in Treatment-Resistant Depression. The American Journal of Psychiatry, 176(6), 428–438. https://doi.org/10.1176/appi.ajp.2019.19020172
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