What the New Data Says
A clinical review published in Psychiatric Times in April 2026 puts the spotlight on a question patients and providers alike have been asking: how often do people stop taking NMDA receptor antagonists — the drug class that includes ketamine and esketamine (Spravato) — and why? The answer, according to the analysis, is more nuanced than a single number. Discontinuation is driven by a specific constellation of side effects, and clinicians can do more to anticipate and manage them rather than treating early dropout as inevitable.
NMDA receptor antagonists have become a central tool in treating treatment-resistant depression (TRD), defined as depression that hasn't responded adequately to at least two antidepressant trials. Both IV ketamine and intranasal esketamine (FDA-approved as Spravato) belong to this class, and both carry known short-term side effects: dissociation, dizziness, nausea, elevated blood pressure, and perceptual disturbances. What this review adds is a closer look at how those side effects translate into real-world dropout rates, and what that means for clinical decision-making timelines.
The core argument from the clinicians cited: treatment teams should track outcomes more systematically — using validated tools like the PHQ-9 depression scale — and make faster, data-informed decisions about dose adjustments or switching to an alternative NMDA agent, rather than continuing an approach that isn't working or that patients can't tolerate.
Understanding the Quality of This Evidence
It's worth being clear about what kind of evidence this represents. This is a clinical review and expert commentary piece — not a new randomized controlled trial. That distinction matters for patients trying to evaluate how much weight to give the findings.
Clinical reviews synthesize existing data and offer expert interpretation, which is valuable for surfacing patterns across multiple studies and translating research into practical guidance. But they're also shaped by the authors' clinical perspectives and the studies they select. This review is making a practice-change argument — urging clinicians to be more proactive — rather than introducing wholly new efficacy or safety data.
What is well-established in the underlying literature: dissociative side effects are common with both ketamine and esketamine, typically peaking during or shortly after infusion or administration and resolving within hours. Cardiovascular effects — elevated blood pressure and increased heart rate — are also documented and require monitoring. The harder question — how often these side effects cause patients to leave treatment altogether — is difficult to pin down because discontinuation rates vary significantly across study designs, patient populations, and clinical settings.
The review's emphasis on PHQ-9 tracking as a tool for faster treatment decisions reflects a broader push in psychiatry toward measurement-based care (MBC), an approach with solid evidence behind it in depression treatment generally. Applying it more rigorously to ketamine and esketamine protocols is a reasonable and well-supported extension of that evidence base.
Key Takeaway for Patients
Side effects from NMDA antagonists like ketamine are common but typically short-lived. New clinical guidance urges providers to monitor patient progress more closely and adjust strategies sooner if someone isn't tolerating or responding to treatment. Asking your prospective provider how they track your progress — and what they do when things aren't working — is one of the most important questions you can ask before starting.
What This Means If You're Considering Ketamine Therapy
For patients and families evaluating ketamine therapy, this review surfaces several practical questions worth raising with any prospective provider.
Ask how your provider tracks progress. The review's emphasis on PHQ-9 monitoring isn't just a clinical technicality — it signals whether a clinic treats you as an active participant in your own care or simply administers sessions on a fixed schedule. Reputable ketamine programs should be tracking your depression severity at each visit and adjusting their approach based on what they find.
Understand the side effect profile before you begin. Dissociation — a feeling of detachment from your body or surroundings — is the most commonly discussed side effect of ketamine and esketamine. For some patients, this experience is tolerable or even meaningful in a therapeutic context; for others, it's distressing enough to prompt discontinuation. A good provider will describe this experience clearly before your first session and have protocols in place for managing it in the moment.
Know that stopping one approach doesn't mean you're out of options. One of the more useful reframings in this review is the message that if one NMDA antagonist isn't working or isn't tolerable, switching — whether that means adjusting the dose, changing delivery format, or trying a different agent — is a legitimate clinical move, not a last resort. Patients should feel empowered to have that conversation rather than assuming they've exhausted all possibilities.
Provider selection matters significantly here. The quality of side effect management and outcome monitoring varies considerably between ketamine clinics. Programs that integrate psychiatric oversight, use validated screening tools, and maintain clear protocols for adverse reactions during sessions are meaningfully different from those offering minimal clinical supervision. When evaluating providers, asking specifically about their monitoring approach and their process when a patient isn't responding is reasonable and appropriate due diligence.
The broader signal from this review is one of increasing maturity in how the field approaches these medications. The initial wave of ketamine adoption was characterized by enthusiasm around rapid antidepressant effects; the current moment is about refinement — understanding who benefits, who drops out, and how to improve the likelihood of reaching remission rather than simply initiating treatment. For patients with treatment-resistant depression who have struggled to find relief, that trajectory is ultimately encouraging. It reflects a field taking these tools seriously enough to interrogate them rigorously rather than accepting early results at face value.
Source: Psychiatric Times, April 2026
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