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.
Depression Treatments Compared: IV Ketamine, Spravato, SSRIs, and Oral Ketamine Outcomes
How Effective Are IV and Injection Ketamine for Treating Depression?
Across multiple systematic reviews and meta-analyses, IV ketamine (and, in smaller datasets, intramuscular injection) shows rapid, clinically meaningful benefits for treatment-resistant depression:
- Rapid relief: Significant antidepressant effects can appear within
24 hours of a single IV infusion. - Response rates: About
30%–76%
of patients achieve at least a 50% drop in depression scores, with a median response around 55%. - Remission rates: Roughly
27%–43%
reach minimal or no symptoms (remission), with a median remission rate of 29%. - Effect on suicidal thoughts: Some trials report marked reductions in suicidal ideation within about
40 minutes
of an infusion. - Duration: Antidepressant effects from a single infusion generally last up to
7 days, and can persist longer when infusions are repeated.
See the full findings in the detailed evidence review (viewable as a PDF in your browser or downloadable for later reference).
What Do Systematic Reviews Say About IV Ketamine?
Meta-analyses of IV ketamine for major depression and treatment-resistant depression consistently show rapid, robust symptom reductions after very few treatments.
- After a single infusion, response rates commonly fall in the 50%–70% range, with
remission in about 20%–40% of patients after one or two infusions. - Several reviews report that serial infusions over 2–4 weeks can raise remission rates to around
40%, although most of the underlying studies still used very short protocols (most often one or two infusions). - These findings underline ketamine’s role as a fast-acting intervention, especially in severe or treatment-resistant cases.
Detailed IV Ketamine Results from Clinical Trials
- IV ketamine reliably produces rapid antidepressant effects, often within 24 hours of a single infusion.
- Across controlled studies, response rates generally range from 45% to 65%, compared with
about 5%–20% in placebo groups. - Remission after one infusion is seen in up to 30% of patients – notable given the minimal number of treatments involved.
- Some trials document steep drops in suicidal ideation within roughly 40 minutes, though not every study finds these early anti-suicidal effects to be statistically robust.
- For many patients, benefits last up to a week after a single infusion, and may persist longer when infusions are repeated in a series.
Clinical Trial Results vs Real-World Outcomes
As with many psychiatric treatments, response rates in carefully controlled trials are higher than in routine clinical practice.
- In controlled studies, IV ketamine shows response rates of roughly 63%.
- In real-world cohorts, response settles closer to 30%.
- This pattern appears across five large systematic reviews and meta-analyses published between 2014 and 2024.
Why Individual Long-Term Studies Don’t Settle the Question
Several single studies report striking longer-term outcomes, but they have important limitations and were not included in the core systematic-review-based estimates:
- An open-label trial reported a 79% remission rate at 9-month follow-up, but lacked randomized, controlled design.
- Another study found 69% of patients with suicidal ideation reached full remission of suicidal thoughts after six infusions over four weeks, but did not report overall depression remission rates.
- A 12-month follow-up based on six infusions showed a 46% remission rate.
These findings are encouraging, but because they are not randomized controlled trials and are not synthesized across multiple studies, they sit outside the main systematic-review evidence base on long-term efficacy and safety.
IV vs Injection (IM) Ketamine
IV ketamine has the largest and most developed evidence base. Smaller studies of intramuscular (IM) ketamine suggest similar antidepressant benefits, but injection data are far more limited, so most conclusions about effectiveness still rest on IV infusion trials.
Systematic Reviews and Meta-Analyses on IV Ketamine’s Effectiveness
Therapeutic Advances in Psychopharmacology (2023)
“Ketamine for Bipolar Depression: An Updated Systematic Review.”
About 48% of IV ketamine patients reached ≥50% symptom reduction compared with 5% in the placebo group. In controlled trials, the overall response rate was roughly 63%, while real-world studies showed about 30% responding. Some reductions in suicidal ideation were observed, although results varied between studies.
Brain Sciences (2023)
“An Update on the Efficacy of Single and Serial Intravenous Ketamine Infusions and Esketamine for Bipolar Depression.”
IV ketamine reduced MADRS depression scores by about 11–12 points within two days. Response rates were approximately 54% for a single infusion and 55% for serial infusions, with remission rates around 30% (single) and 40% (serial). Data on esketamine were more limited but showed similar MADRS score reductions. A drop of 11–12 points on MADRS is considered a large, clinically meaningful change, often translating into noticeable improvements in day-to-day functioning.
Current Neuropharmacology (2014)
“The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review.”
Reported a 65% response rate within 24 hours of a single IV infusion. Suicidal ideation often decreased within about 40 minutes and stayed lower for several hours. Some patients maintained remission for up to three months, and repeated infusions extended the duration of antidepressant effects.
Frontiers in Psychiatry (2024)
“Efficacy and Safety of Ketamine and Esketamine for Unipolar and Bipolar Depression: An Overview of Systematic Reviews with Meta-Analysis.”
Found that ketamine significantly increased short-term response and remission versus placebo overall. Effects were strongest in unipolar depression; results for bipolar depression were more mixed, with many studies showing no significant advantage over placebo after one to two weeks.
Molecular Psychiatry (2022)
“International Pooled Patient-Level Meta-Analysis of Ketamine Infusion for Depression: In Search of Clinical Moderators.”
At 24 hours, response rates were 45.5% for ketamine vs 20.5% for placebo (number needed to treat, NNT ≈ 4). At 7 days, response was 37.7% vs 18.3% (NNT ≈ 5.2). Remission occurred in 27% vs 13% at 24 hours, and 25% vs 12% at 7 days, again favoring ketamine.
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.
How Effective is Oral Ketamine in Treating Depression?
Important starting point: The oral ketamine evidence base is small, methodologically weak, and inconsistent. Several meta-analyses find statistically significant symptom reductions, but it’s unclear whether these benefits are strong or reliable enough to produce meaningful, predictable improvement for most patients.
- Across four systematic reviews, oral ketamine shows signals of antidepressant benefit, but with a slower onset and more modest impact than IV ketamine or esketamine.
- Symptom improvement typically appears after
2–6 weeks of treatment, mirroring traditional antidepressants rather than the rapid action of IV ketamine. - Some meta-analyses report a
moderate effect size (e.g., SMD ≈ −0.75), but reviewers question whether this reliably translates into clear day-to-day benefit. - Pooled response/remission risks (~2.6–2.8 vs placebo) sit at the edge of statistical significance (p ~ 0.06–0.07), making robustness and reproducibility uncertain.
- Study quality is a major limitation: small samples, high risk of bias, short follow-up, and inconsistent adverse-event reporting.
- Oral ketamine likely has some antidepressant effect, but the data are too thin to support strong claims about routine, real-world usefulness.
- Unlike IV or esketamine (hours–days), oral formulations take weeks to show benefit, acting more like conventional antidepressants.
- Effects that are statistically significant are not clearly large or consistent enough to be confidently clinically meaningful for most patients.
- Response and remission estimates are tentative, and heavily constrained by trial design and sample size.
- Overall, oral ketamine shows early promise, but it does not yet have the strong, consistent evidence needed for guideline-level recommendations.
“Oral Ketamine for Depression: A Systematic Review.” Statistically significant symptom improvements appeared after
~2–6 weeks, with no immediate effect and unclear real-world clinical impact.
Meta-analysis: moderate symptom reduction (SMD ≈ −0.75) and patients ~2.6–2.8× more likely to respond/remit than placebo, but effects only marginally significant and based on small, heterogeneous trials.
Updated review: all included studies reported symptom improvement with oral ketamine, but randomized controlled data remained sparse and methodologically limited, reinforcing the need for better trials.
Ketamine Infusion vs Spravato: Effectiveness for Depression
Across placebo-controlled trials synthesized in 12 systematic reviews, there are no direct head-to-head studies, but the direction is consistent:
IV racemic ketamine produces larger, faster, and more reliable antidepressant effects than intranasal esketamine (Spravato).
- Symptom reduction: one review found
IV ketamine nearly 5× more effective
than esketamine at lowering depression scores. - Response likelihood: patients on IV ketamine were
about 3× 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 vs placebo:
IV ketamine RR ≈ 3.78
vs
esketamine RR ≈ 1.28. - Speed of relief:
day-1 effectiveness favored IV ketamine by ~4.8×.
- One review: response ~3× higher with IV ketamine (3.01 vs 1.38).
- Another: racemic ketamine showed a 118% higher response rate than esketamine (~2.18× more effective).
More patients cross the “clinically improved” threshold on IV ketamine, even though the comparisons are indirect.
- Day-1 advantages favored IV ketamine by ≈4.8×.
If speed is critical, IV ketamine tends to deliver relief much earlier than the nasal spray.
- IV ketamine vs placebo: RR ≈
3.78 (95% CI: 2.44–5.78)
– remission almost four times more likely than placebo. - Esketamine vs placebo: RR ≈
1.28 (95% CI: 1.11–1.47)
– a relatively small improvement over placebo. - Across reviews, one analysis found
IV ketamine’s remission rate about 2.52× higher
than esketamine’s (RR 3.70 vs 1.47).
- One analysis: racemic ketamine’s remission rate 152% higher than esketamine’s.
- Another: IV ketamine ≈2.52× more effective at ending depression.
Esketamine has a role, but IV ketamine more often delivers complete resolution of symptoms.
Ketamine Effectiveness FAQ: IV Infusions, Spravato, Oral Ketamine and SSRIs Compared
How Effective Is Ketamine Therapy For Depression Compared With SSRIs?
- IV ketamine: response 45–65%, remission 27–43%, relief within hours–days after 1–2 infusions (almost all short-term data).
- Spravato (esketamine): response 49–77% (median 53%), remission 32–58% (median 39%), but based largely on manufacturer-sponsored trials over 8–21 sessions.
- SSRIs: response 35–50%, remission 20–30%, with improvement only after about 2–6 weeks.
- Oral/sublingual ketamine: weakest track record; no reliable response/remission rates, slow onset (2–6+ weeks), and highly variable benefit.
How Fast Can IV Ketamine Start Working, And How Long Do Results Last?
- Effects may begin within hours, even after a single infusion.
- Up to 70% of patients respond to one dose; remission after 1–2 infusions is roughly 20–40%.
- Most studies cover only 1–2 short-term infusions; without maintenance, benefits often fade over days to a few weeks.
What Are Typical Response And Remission Rates For IV Ketamine?
- Controlled trials: response 45–65%; real-world clinics around 30%.
- Remission: typically 27–43%, and up to 40% over 2–4-week series.
- Up to 30% may reach remission after just one infusion; effects can last up to 7 days from a single dose.
What Are Typical Response And Remission Rates For The Esketamine Nasal Spray Spravato?
- Response 49–77% (median 53%); remission 32–58% (median 39%).
- Effect size is modest (≈0.15–0.23) despite long induction series (8–21 sessions over 2–6 months).
- Almost all key trials are industry-sponsored; independent reviews usually find lower efficacy. Suicidal ideation can improve within 2–4 hours but is not durable without ongoing treatment.
How Does Esketamine (Spravato) Compare To IV Ketamine On Response And Remission?
- Comparative reviews show IV ketamine is larger, faster, and more reliable overall.
- One analysis: IV ketamine was nearly 5× more effective for symptom reduction; response ~3.0 for IV vs 1.38 for Spravato.
- Effect size: IV d = −0.75 vs Spravato d = −0.38 (p = 0.03).
- Remission vs placebo: IV RR 3.78 vs Spravato RR 1.28; one review found IV remission rates 152% higher and about 4.8× faster on day-1 outcomes.
How Strong Is The Evidence Base For Oral/Sublingual Ketamine, And What Are Realistic Expectations?
- Evidence for oral/sublingual ketamine is methodologically weak with small, biased, and short-term trials.
- No robust, consistent response or remission rates are available.
- Onset is usually 2–6 weeks, and outcomes are unpredictable and often marginal compared with IV ketamine or Spravato.
- Current systematic reviews do not support strong, reliable benefit for most patients or proven long-term effectiveness.