Most people begin depression treatment with medications that aim for slow and steady improvement, not quick shifts. That approach works well for many, but it can leave others waiting through long stretches of trial and error.
When symptoms stay heavy despite multiple attempts, it is natural to wonder whether something that acts differently might offer another path. Ketamine treatment follows a different biological route and, in some cases, a different timeline.
This article walks through those differences step by step and stays grounded in what recent research shows, not what people sometimes wish it would show.
Traditional Antidepressants Are Designed for Gradual Change
Most antidepressants depend on processes that take time, which explains why the waiting period is built into the treatment model. SSRIs and SNRIs adjust serotonin or norepinephrine signaling, but the mood effects usually lag the chemical changes. U.S. mental health agencies still frame it the same way: Benefits tend to emerge over several weeks, sometimes longer, especially when dose adjustments or medication switches enter the picture.
The extensive STAR*D program, which enrolled more than four thousand adults, makes this clearer than any single explanation. Participants received real-world outpatient care, and many did not reach remission after the first medication trial.
A second or third step was often necessary. That pattern does not mean the medications were ineffective. It just shows how depression sometimes unfolds and why patience becomes part of the standard plan during psychiatric treatment.
Ketamine Uses an Entirely Different Biological Pathway
Ketamine’s mechanism sits in another category altogether, and understanding that difference helps make sense of why it might act faster for some people. Traditional antidepressants emphasize monoamines, while ketamine interacts with glutamatergic pathways.
Esketamine is the FDA-approved nasal spray form of ketamine. It works as a non-competitive NMDA receptor antagonist, which makes it different from regular antidepressants. Scientists are still studying what happens next, but many link its effects to synaptic plasticity and faster symptom shifts.
This contrast does not mean ketamine overrides everything we know about depression. It simply works through a system that standard antidepressants do not touch directly. That makes ketamine therapy for depression a distinct option, especially when the usual routes have not provided relief.
The Timeline Difference Is What Patients Notice Most
Speed is not everything in mental health, but it becomes hard to ignore when two treatments operate on dramatically different clocks. Many antidepressants take weeks before benefits take shape. Ketamine-related approaches sometimes create measurable changes on a shorter timeline. The National Institute of Mental Health has even described ketamine’s potential to reduce symptoms within hours, while traditional medications usually take far longer.
In one clinical trial of adults with treatment-resistant depression, esketamine nasal spray was given twice a week and compared with a placebo. The researchers saw improvements as early as 24 hours after the first dose, and those changes continued through the first month.
At the start, most participants were rated as “markedly ill” or worse. By Day 28, that level of severity dropped to about 23–27% in the esketamine groups, while more than half of the placebo group remained in the markedly ill range.
The study shows that ketamine-based treatment can create meaningful change for some patients in a shorter window.
Why Ketamine Treatment Is Considered for Treatment-Resistant Depression
Ketamine is not a first-line therapy, and clinicians rarely introduce it early unless the situation demands urgent attention. Most of the time, it becomes part of the discussion when someone moves into treatment-resistant depression, which usually means they have completed adequate trials of standard antidepressants without reaching remission.
Recent studies compare ketamine to other advanced interventions, and the results show why this option receives serious consideration. A 2023 New England Journal of Medicine trial examined ketamine versus electroconvulsive therapy in nonpsychotic treatment-resistant depression. Response rates reached 55.4% with ketamine and 41.2% with ECT. The comparison surprised some clinicians because ECT has a long history of effectiveness. A 2025 chart review from a psychiatric hospital compared IV ketamine and electroconvulsive therapy (ECT) over about three weeks. Both helped, but ECT came out ahead: About 67% of patients responded to ECT versus about 46% with ketamine, and remission was 60% vs 46%.
The point is not that ketamine fails. It is that depression care is not one-size-fits-all, so clinicians choose the right tool for the right patient instead of assuming one option always works best.
What Responsible Ketamine Care Looks Like in Modern Psychiatric Treatment
The delivery model shapes the treatment as much as the drug does. Ketamine’s short-term effects require observation, so clinics build structured sessions rather than sending patients home with medication.
Esketamine must be administered in certified settings with at least two hours of monitoring. That requirement exists because trial data show side effects clinicians must plan around, including dissociation in 41% of patients compared with 9% receiving a placebo. Sedation reached 23% in active treatment, dizziness 29%, and an increase in blood pressure of about 10%.
These effects are manageable with preparation, but they are not things a patient should monitor alone. The safety database behind esketamine includes 1,709 adults evaluated for treatment-resistant depression, with 30% exposed for at least six months and 11% for at least twelve months.
Those numbers provide reassurance that the approach has been studied beyond the short term, even as questions remain. In practice, supervised sessions combined with ongoing evaluation give ketamine its safest footing inside modern psychiatric treatment.
When the Usual Timeline Is Not Working, We Help You Build a Better Plan
Different treatments naturally move at different speeds, and that shapes how people experience recovery. Traditional antidepressants often unfold slowly, sometimes over several adjustments, and many patients end up needing more than one attempt before things start to shift.
Ketamine treatment usually enters the conversation when that slower path has not brought enough relief or when symptoms make the wait feel unrealistic. It is not a shortcut. It is simply a different approach that requires structure, careful monitoring, and honest follow-up.
At Zeam, we use ketamine as part of a larger care plan, not as a quick fix. If you are considering ketamine therapy for depression, we will review what you have tried, explain what supervised sessions feel like, and map the next steps you can measure over time. If you want a clear recommendation, contact us to talk through whether this approach fits your needs.
Key Takeaways
- Traditional antidepressants such as SSRIs and SNRIs typically require weeks of treatment and dose adjustments before meaningful improvement appears.
- Ketamine and esketamine work through glutamatergic and NMDA-receptor–related pathways, which distinguishes them biologically from monoamine-based antidepressants.
- Research shows ketamine may produce faster symptom reduction for some patients with treatment-resistant depression, including measurable changes within days — and in some cases, hours.
- Esketamine nasal spray must be given in a certified medical setting with monitoring, due to known short-term effects including dissociation, dizziness, sedation, and blood pressure increases.
- Comparative studies show ketamine is not a universal replacement for other advanced interventions such as ECT — instead, it is one clinical option chosen based on patient history and severity.
- Responsible ketamine care includes structured sessions, safety monitoring, ongoing evaluation, and integration into a broader psychiatric treatment plan.
Citations
- Cleveland Clinic Journal of Medicine — treatment-resistant depression and STAR*D outcomes
https://www.ccjm.org/content/ccjom/75/1/57.full.pdf - National Institute of Mental Health — rapid-acting depression research & ketamine mechanisms
https://www.nimh.nih.gov/news/science-updates/2024/new-hope-for-rapid-acting-depression-treatment - Randomized and comparative ketamine research (PMC)
https://pmc.ncbi.nlm.nih.gov/articles/PMC12224050/ - New England Journal of Medicine — ketamine vs. ECT in treatment-resistant depression
https://www.nejm.org/doi/10.1056/NEJMoa2302399 - 2025 chart-review comparison of IV ketamine and ECT
https://pubmed.ncbi.nlm.nih.gov/40541833/ - SPRAVATO® (esketamine) prescribing information & safety monitoring requirements
https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/SPRAVATO-pi.pdf
