Ketamine for Depression

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Lamotrigine, Acamprosate, Memantine, others

Disqualifiers: Pregnancy, Psychosis, Hallucinations, others

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

Compensation: Varies

Number of Visits: 6

Duration: 3 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether intravenous (IV) ketamine can treat depression in patients who have spent a week in the ICU at Mayo Clinic Florida. Participants will receive either ketamine (also known as Ketalar or Special K) or a placebo (a substance with no active drug) to determine if ketamine improves depressive symptoms. Suitable candidates include those diagnosed with conditions like heart disease, kidney failure, or those who have undergone organ transplants and are experiencing moderate to severe depression in the ICU. 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?

The trial requires that you stop taking any medications known to affect the N-methyl-D-aspartate receptor system, such as lamotrigine, acamprosate, memantine, riluzole, or lithium.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketamine is generally safe for treating depression. Most side effects are mild and resolve over time. Common issues include temporary increases in blood pressure and mild mental effects. Serious problems are rare, and most people do not discontinue treatment because of them.

Studies have found that ketamine can quickly improve depression symptoms, sometimes within a day. However, ketamine can be misused, so it should be administered carefully under a doctor's supervision. Overall, the treatment is well-tolerated, with most side effects being manageable. ^{1 2 3 4 5}

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

Researchers are excited about ketamine for depression because it offers a rapid-acting alternative to traditional antidepressants like SSRIs and SNRIs, which often take weeks to work. Unlike these standard treatments, ketamine targets the NMDA receptor in the brain, potentially providing relief from depressive symptoms within hours or days. This fast-acting mechanism is particularly valuable for patients in acute or severe depressive states, offering hope for quicker recovery.

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

Research has shown that ketamine can help treat depression. In one study, participants experienced significant improvement in depression symptoms within 72 hours of receiving a ketamine infusion. Another study found that 52% of participants saw their severe depression remit after just three infusions over 11 days. Ketamine's effects can begin within hours and peak at 24 hours. In this trial, participants in the Ketamine Group will receive intravenous (IV) ketamine to evaluate its effectiveness in quickly relieving depressive symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Devang Sanghavi, MBBS, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for Mayo Clinic Florida ICU patients with depression (PHQ-9 score ≥10) and specific conditions like heart attack, renal failure, COPD. Excluded are those with vital sign instability, ketamine allergy, intracranial issues, psychosis history, extreme weights, substance abuse withdrawal or recent use of hallucinogens including cannabis.

Inclusion Criteria

Has been in the Mayo Clinic Florida ICU for the past 1 week

PHQ-9 score of 10 or higher

I have been diagnosed with a serious heart, lung, liver, or kidney condition, or I am undergoing major surgery.

Exclusion Criteria

Heart rate: < 50 or > 120, or Respiratory Rate: < 10 or > 30

Poor vital sign stability hypoxia: O2 < 95%, hypotension: SBP < 90 hypertension: SBP > 180

Any allergy to ketamine or diphenhydramine

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive intravenous ketamine or placebo infusions

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine Hydrochloride
• Placebo

Trial Overview The study tests if Ketamine Hydrochloride infusions can help ICU patients with depression compared to a placebo. Patients will be randomly assigned to receive either the real drug or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Ketamine Group Experimental Treatment 1 Intervention

Adult patients who have been in the Mayo Clinic Florida ICU for one week with moderate or severe depression will receive intravenous (IV) ketamine

Group II: Placebo Group Placebo Group 1 Intervention

Adult patients who have been in the Mayo Clinic Florida ICU for one week with moderate or severe depression will receive intravenous (IV) placebo

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

Approved in United States as Ketalar for:

• Anesthesia
• Pain management
• Depression
• Suicidal ideation

Approved in European Union as Ketamine Hydrochloride for:

• Anesthesia
• Pain management
• Treatment-resistant depression

Approved in Canada as Ketamine Hydrochloride for:

• Anesthesia
• Pain management
• Depression

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

This systematic review analyzed 60 studies on the safety of ketamine for treating depression, revealing that acute doses of ketamine led to more frequent side effects, including psychiatric and cardiovascular issues, compared to placebo.

There is a notable lack of data on the long-term safety and effects of repeated ketamine dosing, highlighting the need for large-scale clinical trials to better understand its safety profile over extended use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. Short, B., Fong, J., Galvez, V., et al.[2019]

In a study involving 6630 patients treated with repeated parenteral ketamine for depression, only 0.7% experienced adverse effects that required discontinuation, indicating a high safety profile for this treatment.

Among published reports, the rate of significant adverse events leading to treatment discontinuation was low at 1.2%, suggesting that long-term ketamine treatment for depression is reasonably safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Repeated Administration of Parenteral Ketamine for Depression. Feifel, D., Dadiomov, D., C Lee, K.[2020]

Ketamine has been shown to provide rapid antidepressant effects within 24 hours, making it a potential option for patients with treatment-resistant depression, although its long-term efficacy remains unclear.

The safety profile of low doses of ketamine is generally good, but there is insufficient data on the effects of repeated higher doses, highlighting the need for further research on its long-term use in treating depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and depression: a narrative review. Corriger, A., Pickering, G.[2020]

Subcutaneous (SC) administration of racemic ketamine and esketamine has shown rapid and robust antidepressant effects in both unipolar and bipolar patients, with response and remission rates ranging from 50% to 100% after single or multiple doses.

The studies indicated that SC ketamine is generally well-tolerated, with only transitory side effects, making it a promising and cost-effective treatment option for depression, especially in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. Cavenaghi, VB., da Costa, LP., Lacerda, ALT., et al.[2021]

Intranasal (IN) ketamine treatment for depression was found to have significant acute side effects, including cardiovascular and neurological issues, at doses lower than 100 mg, leading to poor tolerability among participants.

The study indicated that the formulation and delivery method of IN ketamine were not effective, as participants struggled with self-administration and experienced variable absorption, suggesting that these factors greatly influence the treatment's safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial. Gálvez, V., Li, A., Huggins, C., et al.[2022]

Ketamine and esketamine demonstrate rapid antidepressant effects, with improvements in clinical response observed within 40 minutes to 1 week for ketamine and 2 hours to 4 weeks for esketamine, along with reductions in depression scores and suicidality.

Despite their effectiveness, the long-term safety and efficacy of ketamine and esketamine remain uncertain, and the overall quality of the studies reviewed was critically low, highlighting the need for more rigorous research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. Lima, TM., Visacri, MB., Aguiar, PM.[2022]

Subanaesthetic doses of ketamine have shown substantial efficacy in treating depression, with response rates averaging 77% and remission rates around 43% within 4 to 72 hours after a single dose.

Despite the rapid improvement in mood for many patients, the effects are often short-lived, highlighting the need for further research on dosing regimens and strategies to maintain the antidepressant response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Katalinic, N., Lai, R., Somogyi, A., et al.[2013]

In a study of 9016 patients receiving ketamine intravenous therapy (KIT) for depression, 53.6% showed a significant response (≥50% reduction in depression scores) within 14-31 days, indicating KIT's efficacy in real-world settings.

While most patients benefited from KIT, a small percentage (8.4%) experienced worsening depressive symptoms, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. McInnes, LA., Qian, JJ., Gargeya, RS., et al.[2023]

A 49-year-old woman with severe treatment-resistant major depression experienced significant improvement after receiving 36 sessions of ketamine intravenous therapy over 10 months, resulting in nearly a 50% reduction in her depressive symptoms.

The case suggests that long-term repeated ketamine therapy could be a viable option for patients with treatment-resistant depression, but further research is needed to determine the best treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. Kwon, JH., Sim, WS., Hong, JP., et al.[2018]

In a European clinical trial, a 55-year-old male with treatment-resistant depression and substance use disorder showed significant improvement in depression symptoms after a single intravenous infusion of ketamine, with reductions in Hamilton Depression Rating Scale (HDRS) scores from 36 to 16 and Beck Depression Inventory (BDI) scores from 26 to 9.

The antidepressant effects of ketamine were rapid, with the patient reporting improvements just 25 minutes into the infusion, and these effects lasted for at least 7 days, demonstrating ketamine's potential as a fast-acting treatment for depression even in patients with co-occurring substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. Liebrenz, M., Borgeat, A., Leisinger, R., et al.[2022]

Citations

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

Efficacy of ketamine therapy in the treatment of depression Results: There was a significant improvement in depression, anxiety, and the severity of illness after 2 weeks and 1 month of the last dose of ketamine.

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

Oral ketamine for the treatment of major depressive and ... Oral ketamine is safe and shows promising efficacy in treating depression. •. Meta-analysis estimated a number needed to treat of 5 for ...

3. michiganmedicine.org michiganmedicine.org/health-lab/ketamines-promise-severe-depression-grows-major-questions-remain

Ketamine's promise for severe depression grows, but major ... After just three infusions of ketamine over 11 days, 52% of participants saw their severe depression ease so much they achieved remission. ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/10686270/

Antidepressant effects of ketamine in depressed patients Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion.

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.710338/full

An Integrative Approach to Ketamine Therapy May ... Results indicated that ketamine had an effect on depressive symptoms within 4 h following a single infusion, with peak efficacy at 24 h.

6. fda.gov fda.gov/drugs/human-drug-compounding/fda-warns-patients-and-health-care-providers-about-potential-risks-associated-compounded-ketamine

FDA warns about compounded ketamine for psychiatric ... Known safety concerns associated with the use of ketamine products include abuse and misuse, psychiatric events, increases in blood pressure, ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1064748125004336

Ketamine and Esketamine for Late-Life Depression Adverse events were generally mild to moderate and discontinuation due to side effects was rare. Cognitive outcomes were mostly stable or ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7073997/

Safety and Tolerability of Ketamine Use in Treatment ... The literature shows that treatment with ketamine is efficacious and safe, and the majority of adverse drug reactions are mild and tend to mostly disappear ...

9. aetna.com aetna.com/cpb/medical/data/900_999/0938.html

Ketamine for the Treatment of Depression and Other ... The authors concluded that ketamine rapidly reduced suicidal thoughts, within 1 day and for up to 1 week in depressed patients with suicidal ideation.