Why Clinicians Are Talking About Dropout Rates
A new analysis published in Psychiatric Times is drawing attention to something patients rarely hear discussed upfront: how often people stop NMDA receptor antagonist treatments — and why. The piece focuses on ketamine and esketamine (brand name Spravato), the two FDA-relevant options in this class, and calls on clinicians to use side effect data and standardized outcome tracking to make faster, better decisions for people with treatment-resistant depression (TRD).
The core argument is straightforward: too many patients linger on a regimen that isn't working, or drop out unnecessarily because side effects weren't anticipated or managed well. The authors push for a more systematic approach — monitoring PHQ-9 depression scores regularly, documenting adverse effects consistently, and being willing to adjust doses or switch treatments sooner rather than later.
What the Side Effect Landscape Actually Looks Like
For patients comparing their options, understanding the side effect profiles of IV ketamine versus intranasal esketamine (Spravato) is genuinely useful. These are not identical drugs administered the same way, and their tolerability data reflects that.
IV ketamine is typically administered in a clinical setting over 40 minutes. The most commonly reported side effects include dissociation (a feeling of detachment from surroundings or self), elevated blood pressure, nausea, and dizziness. These effects are generally short-lived — most resolve within an hour of the infusion ending. Discontinuation rates in clinical practice vary, but dissociative experiences are the most frequent reason patients opt not to continue.
Esketamine (Spravato) is a nasal spray delivered in a certified healthcare setting under the FDA's REMS program, meaning patients must be observed for at least two hours after each dose. Its side effect profile overlaps with IV ketamine — dissociation, dizziness, nausea, sedation — but the route of administration changes the experience. Bioavailability is lower and more variable with nasal delivery, which can affect both efficacy and how intensely side effects are felt from session to session.
The Psychiatric Times analysis reinforces what clinical experience has shown: side effects with both options are real but manageable, and most patients who discontinue do so in the early phases of treatment. Getting that early period right — through expectation-setting, dose calibration, and monitoring — is where providers have the most leverage.
The Case for Faster, Smarter Decision-Making
What makes this analysis particularly relevant for 2026 is its focus on clinical efficiency. Treatment-resistant depression is defined by failure of at least two adequate antidepressant trials — meaning patients who reach ketamine or esketamine have already waited through months or years of ineffective treatment. The authors argue that once a patient starts an NMDA antagonist, providers should not take a passive, wait-and-see approach.
Specifically, they recommend:
- Tracking PHQ-9 scores at regular intervals to objectively measure whether the treatment is working, rather than relying on subjective clinical impression alone.
- Documenting side effects systematically so patterns can be identified and addressed — rather than letting unmanaged adverse effects become a quiet reason patients stop showing up.
- Adjusting doses or switching formulations sooner if initial response is poor. Waiting too long to pivot wastes time patients with TRD don't have.
This is a meaningful shift in framing. The conversation is moving from "is ketamine effective?" — which has been answered affirmatively by a substantial body of evidence — to "how do we use it as effectively as possible for each individual patient?"
Key Takeaway for Patients
If you're starting ketamine or esketamine treatment, ask your provider how they track your progress and how they'll handle it if side effects become a problem. A clinic that monitors your PHQ-9 scores and has a clear protocol for adjusting your treatment is following best practices — and that structure meaningfully improves your chances of reaching remission rather than dropping out early.
What This Means When Comparing Your Options
For people researching ketamine treatment, this analysis is a reminder that the delivery method, clinical setting, and provider approach all shape your experience — not just the drug itself. A well-run IV ketamine program with attentive monitoring may produce very different outcomes than one where patients are treated and sent home without structured follow-up.
Questions worth asking any ketamine clinic or psychiatrist before starting:
- How do you measure whether the treatment is working?
- What's your protocol if I experience significant dissociation or other side effects?
- At what point would you consider adjusting my dose or recommending a different approach?
The science on NMDA antagonists for treatment-resistant depression continues to mature. What this latest clinical guidance signals is that the frontier is no longer just proving these treatments work — it's building the clinical infrastructure to make them work better, faster, and more sustainably for the patients who need them most.
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