Ketamine therapy for depression is an evidence paradox. Clinics often stay vague about real odds of remission. The media pushes psychedelic “miracle cure” headlines. And the research itself? It can whiplash you from one extreme to the other — I’ve seen single studies claiming ketamine doesn’t work at all, and others showing it has up to an 80% remission rate.
So which is it?
To answer that, I did what the typical Google search never will: I dug into every systematic review and meta-analysis on ketamine therapy for depression published in the last five years — 33 in total. This was a deliberate “review of reviews,” the gold standard for seeing what actually holds up across dozens of separate studies.
Yes, there are more systematic reviews out there — but my cut-off was recency (I chose only those studies published between 2019 and 2024). These 33 represent the most current real-world numbers we have, pulling together hundreds of trials to see what patterns stay solid and which ones fall apart.
The evidence is unambiguous: ketamine therapy works, though there are lingering questions about its long-term efficacy. Ketamine can deliver relief at a speed and scale that no standard antidepressant matches — dropping suicidal thoughts within hours, and cutting severe symptoms by half sometimes in just 48 hours.
It’s the strongest short-term tool psychiatry has for people out of other options. However, real questions remain about how long these gains last, how often patients may need repeat treatments, and how best to sustain recovery once that initial lift fades.
How Fast — and How Big — Are the Effects?
One thing the evidence makes clear: speed is ketamine’s superpower. While traditional antidepressants often take four to six weeks to deliver relief — if they work at all — ketamine can drop suicidal thoughts in as little as 40 minutes for some patients. Many systematic reviews report significant symptom relief within 24 hours of a single infusion.
When you look at clinical response rates — patients who see at least a 50% drop in symptoms — the pooled data runs anywhere from 30% to 76%, with a median around 55%. Compare that to SSRIs for treatment-resistant depression: those hover closer to 20%. It’s no contest — for this group, ketamine often triples your odds of meaningful short-term relief.
Remission: The Tougher Prize
If depression is like drowning, “response” is treading water and “remission” is being pulled onto the boat. Ketamine can pull you onto the deck faster than any other antidepressant.
But here’s the catch: that rescue often comes with an asterisk — how long before you fall back into the water?
Getting better is one thing — getting well enough that depression barely registers is another. That’s remission, and for people with treatment-resistant depression, it’s the holy grail.
Across the 33 systematic reviews I pulled together, short-term remission rates for IV ketamine generally range from about 27% to 43%, with some individual studies showing even higher numbers after just one or two infusions. That’s remarkable when you consider that standard SSRIs for this population deliver remission rates closer to 10–20%.
But here’s the catch: almost all IV ketamine studies stop at one or two infusions, sometimes six if you’re lucky. Beyond that, the data simply isn’t there — not because patients drop off a cliff, but because there’s no big pharmaceutical payoff in funding large, long-term trials on generic ketamine.
So the question hangs in the air: Do those impressive short-term remission numbers hold if you keep going? Or does the lift fade if you don’t? And what’s the best way to keep it alive — repeat infusions, booster doses, psychotherapy?
By contrast, intranasal esketamine (Spravato) does have longer-term data because the manufacturer had to present it to the FDA for approval. Those numbers are striking on the surface:
- Remission rate at the maintenance endpoint for younger adults (18–64 years): 56.6%
- Remission rate at the maintenance endpoint for older adults (65+): 64.3%
But when you zoom out to the independent evidence base — the 33 systematic reviews and meta-analyses — those figures don’t hold up as strongly. Across multiple reviews, the real-world remission range for esketamine lands closer to 32%–58%, with a median around 39%.
In other words, the nasal spray has proven it can maintain relief over time — but at a level that’s consistently more modest than the dramatic short-term lift IV ketamine can deliver.
So patients and clinicians face a real-world trade-off: IV ketamine hits harder and faster but leaves unanswered questions about how long the benefit lasts, while esketamine nasal spray is easier to repeat, insurance-approved, and better studied for maintenance — but delivers less punch for many people.
What’s clear is that ketamine therapy works — and it works better and faster than anything else psychiatry has for treatment-resistant depression. What’s not yet clear is how best to turn that breakthrough into lasting recovery.
Not All Routes Deliver the Same Punch
One thing is clear when you compare routes side by side: IV infusions hit the hardest — and fastest. Placebo-controlled studies show IV racemic ketamine can be up to five times more effective than placebo, with a large effect size around –0.75. For people who’ve run out of other options, that immediate, robust lift can be life-changing.
Esketamine nasal spray delivers a more modest impact. Across systematic reviews, its real-world effect size lands closer to –0.38 — about half the punch of IV ketamine. But it’s easier to access, insurance-approved, and better studied for longer-term use because the manufacturer had to present maintenance data to the FDA.
Oral ketamine is often seen as the most convenient route — no IV drip, no nasal spray clinic visits — but the evidence shows it’s the slowest and least reliable way to get the antidepressant benefits people hope for.
And even then, that improvement comes with a big caveat: the studies so far are small, the results are right on the edge of what researchers consider truly reliable, and the evidence is anything but rock solid. Systematic reviews repeatedly flag issues like tiny sample sizes and short follow-up periods.
In plain terms, oral ketamine is a slow burn. For some patients, it may help over time — but if you’re hoping for the rapid, dramatic lift that IV ketamine can deliver, the oral version is more like a standard antidepressant with a ketamine label. It’s a trickle when some patients need a firehose.
So, Overhyped, Underrated — or Both?
33 systematic reviews and meta-analyses settle one thing: ketamine therapy is no fringe fad. For treatment-resistant depression, it delivers the fastest relief we’ve ever seen — sometimes tripling the odds of improvement compared to traditional meds. For some, that means suicidal thoughts drop like a stone in hours.
But the same reviews expose what the headlines leave out: the effect often fades without repeat treatments, the long-term risks and benefits are still murky, and a single “miracle session” won’t carry you all the way to lasting recovery.
For patients and practitioners alike, the real takeaway is honest: ketamine is both overhyped and genuinely powerful. When used wisely — alongside therapy, careful planning, and realistic expectations — it can buy precious time. But it’s not a magic bullet.
-By Michael Alvear
