Ketamine for Depression

(G2K Trial)

Overseen By Nicole Reinicke

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Benzodiazepines, MAOIs, Opioid antagonists, others

Disqualifiers: Schizophrenia, Bipolar, Substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how ketamine, administered through an IV, affects brain chemicals linked to depression. Researchers compare these effects to a placebo (a harmless substance with no active ingredient) to determine if ketamine can aid those with treatment-resistant depression. It targets individuals who have tried at least two antidepressants without success and exhibit high levels of depression symptoms. Participants must not have certain mental health conditions, use specific medications, or have unstable medical problems. The goal is to discover new ways to manage depression when other treatments have failed. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. Specifically, medications affecting glutamate or GABA, monoamine oxidase inhibitors, opioid antagonists, and certain CYP3A4 inducers must be stopped two weeks before the study and for at least 24 hours after the last dose of the study drug.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ketamine is being explored as a treatment for depression, particularly when other treatments have failed. Studies suggest ketamine holds promise for individuals with treatment-resistant depression, but awareness of potential side effects is crucial.

Ketamine is generally well-tolerated, though some side effects may occur. Common side effects include dizziness, increased heart rate, and confusion. Some individuals might also experience nausea or a temporary sense of disconnection from reality. Serious side effects, such as breathing problems, can occur if the drug is administered too quickly or in high doses, but these are typically managed with medical assistance.

Overall, ketamine has been safely used in medical settings, such as during surgeries, indicating its potential safety for treating depression. Prospective trial participants should discuss any concerns with the study team or a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Unlike traditional antidepressants that typically alter neurotransmitter levels over weeks, ketamine offers a rapid-acting alternative for treating depression. This treatment is unique because it targets the NMDA receptor in the brain, which is different from the usual serotonin or norepinephrine pathways used by standard medications like SSRIs and SNRIs. Researchers are excited about ketamine because it can produce antidepressant effects in just hours, providing quicker relief for patients who might not respond to conventional therapies.

What evidence suggests that ketamine might be an effective treatment for depression?

Research shows that ketamine, which participants in this trial may receive, can quickly and effectively reduce symptoms of depression. One study found that participants felt better immediately after receiving ketamine, with improvements lasting up to a month. This offers hope for people with treatment-resistant depression, where other medications have failed. Ketamine works by altering certain brain chemicals, which can elevate mood. While more research continues, current evidence suggests ketamine effectively treats depression. ^{6 7 8 9 10}

Who Is on the Research Team?

Balwinder Singh, M.D., M.S.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with treatment-resistant depression, which means their condition hasn't improved after trying other medications. Participants must be diagnosed with Major Depressive Disorder and not have schizophrenia.

Inclusion Criteria

Ability to provide informed consent

PHQ-9 total score ≥ 15 at screening

Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria

Exclusion Criteria

I have had bleeding in my brain before.

I have had a brain injury that caused me to lose consciousness.

I have been diagnosed with Complex Regional Pain Syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 40-minute IV infusion of either racemic ketamine or normal saline in an MRI scanner

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in depression severity and biochemical markers up to 24 hours post-infusion

1 day

1 visit (in-person)

Open-label extension (optional)

Participants may opt into an additional open-label ketamine infusion

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study tests if Ketamine given through an IV can help improve symptoms of depression compared to a saline solution (salt water). Researchers will measure changes in brain and blood chemicals related to mood before and after the infusion.

How Is the Trial Designed?

Group I: Ketamine Group Experimental Treatment 1 Intervention

Subjects will receive IV racemic ketamine at a dose of 0.5 mg per kg of the participant's actual body weight, with a maximum dose of 50 mg for individuals weighing over 100 kg.

Group II: Normal Saline/Placebo Group Placebo Group 1 Intervention

Subjects will receive an IV infusion of normal saline over a duration of 40 minutes

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6767816/

Efficacy of ketamine therapy in the treatment of depression Ketamine has a robust and rapid effect on depression, which was seen immediately after the administration of ketamine and sustained at the end of 1 month.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0165032725019081

Oral ketamine for the treatment of major depressive and ... Our findings align with recent data from RCTs showing a positive but non-significant trend for antidepressant efficacy of low-dose peroral ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ibra.12094

Ketamine as a therapeutic agent in major depressive ... In this article, the effectiveness of ketamine as a potential therapeutic for PTSD and MDD along with its mechanisms of action, clinical trials, and possible ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01945047

Action of Ketamine in Treatment-Resistant Depression Results from this study will help establish the beneficial effects of a single KET injection ... Ketamine for use in relief of Major Depressive Disorder ...

5. medrxiv.org medrxiv.org/content/10.1101/2025.03.21.25324252v2.full.pdf

Oral Ketamine for the Treatment of Depression Our findings align with recent data from RCTs showing a positive but non-significant trend for antidepressant efficacy of low-dose peroral ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf

KETALAR (ketamine hydrochloride) injection Respiratory depression may occur with overdosage or too rapid a rate of administration of KETALAR, in which case supportive ventilation should be employed.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470357/

Ketamine - StatPearls - NCBI Bookshelf - NIH A recent randomized controlled trial demonstrated promising results of ketamine for treatment-resistant depression.[26]. Go to: Adverse ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/ketamine-injection-route/description/drg-20075559

Ketamine (injection route) - Side effects & uses Ketamine injection is used alone or together with other medicines to produce loss of consciousness before and during surgery or a medical procedure.

9. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=14017

Ketalar® Injection (Ketamine Hydrochloride) Some neonates exposed to ketamine at maternal intravenous doses ≥1.5 mg/kg during delivery have experienced respiratory depression and low Apgar scores ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12298542/

Pharmacokinetics, Safety, and Tolerability of (R)-Ketamine ... The overall data indicated that (R)-ketamine hydrochloride injection has a favorable safety and tolerability, which can also support further ...