How Effective Is Ketamine Therapy for Depression?
By Michael Alvear, Health Author & Independent Researcher
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Ketamine treatments dramatically outperform traditional antidepressants, with IV ketamine showing the strongest results. SSRIs achieve remission rates of just 20-30%, while ketamine treatments reach 27-58% remission rates—often nearly doubling your chances of recovery. IV ketamine helps 45-65% of patients with relief often starting within hours versus the 2-6 weeks SSRIs require to even begin working, and up to 40% achieve remission after a short series. Spravato nasal spray is less effective than IV, requires months of treatment, and benefits often fade when stopped. Oral ketamine has weak evidence and slow onset.
Does Ketamine Therapy Work For Depression?
If you’re considering ketamine therapy for depression, you’re probably asking yourself the same question that brings most people to this treatment: Will this actually help me feel better?
It’s a fair question—and an important one. The decision to try ketamine therapy carries real costs in money, time, and logistics. You deserve clear, evidence-based answers before making that investment in your mental health.
When we talk about whether ketamine “works,” we’re really asking three fundamental questions: Does it work? How well? And compared to what?
That last question—compared to what—is crucial for understanding ketamine’s true effectiveness. Raw numbers and percentages are helpful, but they don’t tell the complete story. What really matters is how ketamine stacks up against the treatments you might already know about or have tried.
That’s why we’ve compared ketamine’s effectiveness directly to SSRIs—the standard antidepressants used by tens of millions of people worldwide. Think medications like Prozac, Zoloft, or Lexapro. If you’ve struggled with depression, chances are you’ve encountered these medications at some point in your journey.
To give you the most reliable picture, we reviewed high-quality research from 2020–2024, focusing on systematic reviews and meta-analyses—the gold standard of medical evidence. We looked at all delivery methods: IV ketamine, injections, intranasal esketamine (Spravato), oral and sublingual ketamine, and combinations with psychotherapy.
Here’s what the evidence shows:
| Treatment Type | Response Rates (50%+ Reduction in Symptoms) |
Remission Rates (Little to no symptoms) |
Time to Clinical Response (How long it takes to measurably feel better) |
|---|---|---|---|
| IV/Injection Ketamine* | 30-76% | 27-43% | 2-4 hours |
| Esketamine Nasal Spray (Spravato)** | 49-77% | 32-58% | 1-7 days |
| SSRIs*** | 35-50% | 20-30% | 2-6 weeks |
| Oral/Sublingual Ketamine**** | Nothing declarative but evidence is weak | Nothing declarative but evidence is weak | 2-6 weeks |
Frequently Asked Questions
How Effective Is Ketamine Therapy For Depression Compared With SSRIs?
IV ketamine stands out for delivering lightning-fast results in the short term: response rates in controlled studies range from 45–65%, while remission rates sit between 27–43%. Most patients report relief within hours to days after a single or double infusion. However, nearly all IV ketamine studies are short-term and cover just one or two infusions, leaving us with no robust data about medium- or long-term durability, relapse rates, or real-world maintenance.
Spravato (esketamine nasal spray) posts impressively high numbers in published studies—response rates of 49–77% (median 53%) and remission rates of 32–58% (median 39%). In fact, these raw numbers sometimes surpass IV ketamine; but nearly all pivotal Spravato studies are sponsored and run by the manufacturer, Johnson & Johnson. Independent analyses almost always report more modest outcomes, and industry influence raises questions about bias and real-world effectiveness. Spravato usually requires much longer induction series (8–21 treatments over several months), unlike the short-burst IV studies.
Placebo-controlled studies consistently show IV ketamine can be up to five times more effective than esketamine for symptom reduction. IV ketamine is also three times more likely to produce a treatment response compared to the nasal spray.
SSRIs: 35–50% response and 20–30% remission, but patients must wait 2–6 weeks for symptoms to improve.
Oral and sublingual ketamine have the weakest track record. There are no reliable response or remission rates, onset is slow (2–6 weeks plus), and effectiveness is unpredictable and generally poor compared with IV or Spravato.
How Fast Can IV Ketamine Start Working, And How Long Do Results Last?
Effects may begin within hours—even after a single infusion, with up to 70% of patients responding to one dose. Remission rates after one or two infusions are 20–40% (measured in days, not weeks). But nearly all IV studies only test 1–2 infusions, short-term (days to a few weeks): there is minimal medium- or long-term data, and most benefit fades rapidly unless maintenance treatment continues.
What Are Typical Response And Remission Rates For IV Ketamine?
In controlled trials, response is 45–65% (real-world clinics ~30%), and remission is 27–43% (up to 40% over 2–4 weeks). Up to 30% achieve remission from just one infusion. Effects begin within hours (sustained up to 7 days after a single dose).
What Are Typical Response And Remission Rates For The Esketamine Nasal Spray Spravato?
Response rate is 49–77% (median 53%); remission is 32–58% (median 39%). Effect size is modest (0.15–0.23). Most data covers long induction series (8–21 sessions, over 2–6 months)—treatment is both longer and costlier than IV. Nearly all pivotal studies are manufacturer sponsored; independent reviews report lower efficacy. Suicidal ideation can improve within 2–4 hours, but this is not durable over 28 days unless treatment continues.
How Does Esketamine (Spravato) Compare To IV Ketamine On Response And Remission?
Comparative reviews show IV ketamine is consistently larger, faster, and more reliable. One analysis found IV ketamine was nearly 5× more effective for symptom reduction. Response: IV ~3.0, Spravato 1.38. Effect size: IV (d = −0.75) vs Spravato (d = −0.38, p = 0.03). Remission vs placebo: IV (RR 3.78), Spravato (RR 1.28)—IV remission is almost four times more likely. Additional analyses: IV remission rate was 152% higher than Spravato’s. IV ketamine also provides relief ~4.8× faster for “day-1” outcomes. Most Spravato studies are industry funded; IV trials are rarely medium/long-term and usually for just 1–2 sessions.
How Strong Is The Evidence Base For Oral/Sublingual Ketamine, And What Are Realistic Expectations?
The evidence base for oral/sublingual ketamine is methodologically weak. No credible or consistent response/remission rates have been published. Onset is much slower—usually 2–6 weeks—and outcomes are unpredictable and marginal. Systematic reviews do not support a reliable benefit for most patients, and meaningful, long-term effectiveness remains unproven.
How Well Does Esketamine (Spravato) Work for Depression
Key Findings at a Glance
It’s important to flag something here: Unlike IV ketamine studies which looked at 1 or 2 treatments over the course of 1-7 days, most of the analyses done on Spravato looked at 8-21 treatments over the course of 2-6 months. Why? Short answer: Pharmaceuticals have the money to spend on medium and long-term studies.
- Response rates: 49%–77% (median 53%).
- Remission rates: 32%–58% (median 39%).
- Effect size: modest overall impact (0.15–0.23).
- Duration: benefits often diminish after stopping treatment.
- Common side effects: dissociation, dizziness, nausea, sedation/somnolence, elevated blood pressure.
Spravato Depression Results: Response and Remission
Across six systematic reviews (2020–2024), response ranges from 49% to 77% (median 53%), and remission from 32% to 58% (median 39%). These figures describe the Spravato nasal spray success rate in depression during the induction phase and helps frame Spravato’s effectiveness for treatment-resistant depression in medium to long-term.
Impact on Suicidal Thinking
Several reviews noted improvements in suicidal ideation within 2–4 hours, but gains typically faded by 24 hours and were not significant at 28 days without ongoing treatment and support.
Does Spravato Nasal Spray Work Long Term for Depression?
Continuing beyond the 4-week induction can help prevent relapse, but relief often diminishes after discontinuation.
Safety Profile: What to Expect
Common Adverse Events
- Dissociation (feeling detached), dizziness, nausea
- Sedation or somnolence
- Elevated blood pressure
These events are commonly reported and generally managed with clinic monitoring.
Reporting Gaps
One systematic review found that several trials underreported serious and non-serious adverse events relative to their trial registries, especially psychiatric and cardiovascular events. Not all reviews echoed this, but it reinforces the value of independent scrutiny.
Ketamine Infusion vs Spravato: Effectiveness for Depression
There are no head-to-head trials, but across 12 systematic reviews and meta-analyses comparing separate placebo-controlled studies, the direction is consistent. When weighing Spravato vs IV ketamine effectiveness for depression, IV racemic ketamine shows larger, faster, and more reliable effects than intranasal esketamine.
IV vs Nasal Spray Ketamine: Effectiveness in Depression at a Glance
- Symptom reduction: one review found IV ketamine nearly five times more effective than esketamine at lowering depression scores.
- Response likelihood: patients on IV ketamine were about three times more likely to respond than those on esketamine (3.01 vs 1.38).
- Effect size: racemic ketamine d = −0.75 vs esketamine d = −0.38 (p = 0.03).
- Remission likelihood vs placebo: IV ketamine RR = 3.78; esketamine RR = 1.28.
- Speed of relief: day-1 effectiveness favored IV ketamine by about 4.8×.
Spravato vs IV Ketamine Effectiveness for Depression: What Moves Scores Farther?
Placebo-Controlled Signals Favor IV Ketamine
- Across pooled analyses, ketamine infusion vs Spravato effectiveness in depression favored IV ketamine for larger symptom drops.
- In one review, IV ketamine was nearly five times more effective for symptom reduction.
- Response advantage: 3.01 for IV ketamine vs 1.38 for esketamine.
- Effect sizes on standardized scales: IV d = −0.75; esketamine d = −0.38.
Interpretation: tested separately against placebo, IV ketamine shifts depression scores farther and more consistently than the nasal spray.
How Big Is the Gap?
- One meta-analysis reported an extremely large effect for IV ketamine (Hedges’ g = 1.52).
- Standardized mean differences: ketamine −0.61 and −0.55 vs esketamine −0.22 and −0.15.
Interpretation: the IV vs nasal spray ketamine effectiveness in depression gap shows up across multiple metrics, with IV producing a larger drop in severity.
Who Improves More Often?
- One review: response about three times higher with IV ketamine (3.01 vs 1.38).
- Another: racemic ketamine showed a 118% higher response rate than esketamine, roughly 2.18× more effective.
Interpretation: more patients reach improvement thresholds on IV ketamine. While these are indirect comparisons, the advantage consistently points to IV.
How Fast Do Results Appear?
- Day-1 advantages favored IV ketamine by approximately 4.8×.
Interpretation: if speed matters, IV ketamine tends to deliver relief earlier than esketamine.
Remission: Which Option Ends Symptoms More Often?
Remission Odds vs Placebo
If you’re deciding between options, it helps to know not just whether a treatment works, but how often it gets people all the way to no or near-no symptoms. Below is a quick, plain-English read of what the research shows about IV ketamine and esketamine (Spravato) compared with placebo.
What “Remission” and “Placebo” Mean
Again, remission means depression symptoms drop to none or almost none. Placebo is the comparison group receiving a dummy treatment under the same study conditions.
What the Numbers Say
- IV ketamine vs placebo: Risk ratio (RR) ≈ 3.78 (95% CI: 2.44–5.78). That means remission was almost four times more likely than in the placebo group.
- Esketamine vs placebo: RR ≈ 1.28 (95% CI: 1.11–1.47). That’s a small increase over placebo.
- Across reviews: One analysis found IV ketamine’s remission rate about 2.52 times higher than esketamine’s (RR 3.70 vs 1.47).
Consistent Advantage Across Reviews
- One analysis: racemic ketamine’s remission rate 152% higher than esketamine’s.
- Another: IV ketamine 2.52× more effective at ending depression.
Interpretation: esketamine helps some patients, but IV ketamine more frequently delivers complete resolution.
Ketamine Infusion vs Spravato: Effectiveness for Depression
There are no head-to-head trials, but across 12 systematic reviews and meta-analyses comparing separate placebo-controlled studies, the direction is consistent. When weighing Spravato vs IV ketamine effectiveness for depression, IV racemic ketamine shows larger, faster, and more reliable effects than intranasal esketamine.
IV vs Nasal Spray Ketamine: Effectiveness in Depression at a Glance
- Symptom reduction: one review found IV ketamine nearly five times more effective than esketamine at lowering depression scores.
- Response likelihood: patients on IV ketamine were about three times more likely to respond than those on esketamine (3.01 vs 1.38).
- Effect size: racemic ketamine d = −0.75 vs esketamine d = −0.38 (p = 0.03).
- Remission likelihood vs placebo: IV ketamine RR = 3.78; esketamine RR = 1.28.
- Speed of relief: day-1 effectiveness favored IV ketamine by about 4.8×.
Spravato vs IV Ketamine Effectiveness for Depression: What Moves Scores Farther?
Placebo-Controlled Signals Favor IV Ketamine
- Across pooled analyses, ketamine infusion vs Spravato effectiveness in depression favored IV ketamine for larger symptom drops.
- In one review, IV ketamine was nearly five times more effective for symptom reduction.
- Response advantage: 3.01 for IV ketamine vs 1.38 for esketamine.
- Effect sizes on standardized scales: IV d = −0.75; esketamine d = −0.38.
Interpretation: tested separately against placebo, IV ketamine shifts depression scores farther and more consistently than the nasal spray.
How Big Is the Gap?
- One meta-analysis reported an extremely large effect for IV ketamine (Hedges’ g = 1.52).
- Standardized mean differences: ketamine −0.61 and −0.55 vs esketamine −0.22 and −0.15.
Interpretation: the IV vs nasal spray ketamine effectiveness in depression gap shows up across multiple metrics, with IV producing a larger drop in severity.
Who Improves More Often?
- One review: response about three times higher with IV ketamine (3.01 vs 1.38).
- Another: racemic ketamine showed a 118% higher response rate than esketamine, roughly 2.18× more effective.
Interpretation: more patients reach improvement thresholds on IV ketamine. While these are indirect comparisons, the advantage consistently points to IV.
How Fast Do Results Appear?
- Day-1 advantages favored IV ketamine by approximately 4.8×.
Interpretation: if speed matters, IV ketamine tends to deliver relief earlier than esketamine.
Remission: Which Option Ends Symptoms More Often?
Remission Odds vs Placebo
If you’re deciding between options, it helps to know not just whether a treatment works, but how often it gets people all the way to no or near-no symptoms. Below is a quick, plain-English read of what the research shows about IV ketamine and esketamine (Spravato) compared with placebo.
What “Remission” and “Placebo” Mean
Again, remission means depression symptoms drop to none or almost none. Placebo is the comparison group receiving a dummy treatment under the same study conditions.
What the Numbers Say
- IV ketamine vs placebo: Risk ratio (RR) ≈ 3.78 (95% CI: 2.44–5.78). That means remission was almost four times more likely than in the placebo group.
- Esketamine vs placebo: RR ≈ 1.28 (95% CI: 1.11–1.47). That’s a small increase over placebo.
- Across reviews: One analysis found IV ketamine’s remission rate about 2.52 times higher than esketamine’s (RR 3.70 vs 1.47).
Consistent Advantage Across Reviews
- One analysis: racemic ketamine’s remission rate 152% higher than esketamine’s.
- Another: IV ketamine 2.52× more effective at ending depression.
Interpretation: esketamine helps some patients, but IV ketamine more frequently delivers complete resolution.