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

Trial Summary

What is the purpose of this trial?

This trial is studying the effects of giving ketamine through a vein to ICU patients with depression. These patients are chosen because they might not respond to usual treatments. Ketamine helps by changing brain chemicals to improve mood quickly. Ketamine has been investigated as a potential antidepressant option for treatment-resistant depression, showing rapid and robust effects.

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.

What evidence supports the effectiveness of the drug Ketamine Hydrochloride for treating depression?

Research shows that ketamine, originally used as an anesthetic, can quickly improve symptoms in people with severe depression, even when other treatments haven't worked. Although the effects of a single dose may not last long, repeated treatments might provide longer relief. ^{1 2 3 4 5}

Is ketamine safe for treating depression?

Research shows that ketamine can cause side effects like psychological distress, bladder issues, and cognitive decline, but these are rare. Most people tolerate it well, and only a small percentage need to stop treatment due to side effects. ^{6 7 8 9 10}

How is ketamine different from other drugs for depression?

Ketamine is unique because it works quickly to relieve depression symptoms, often within hours, unlike traditional antidepressants that can take weeks. It is administered in different ways, such as intravenously or intranasally, and is particularly considered for treatment-resistant depression, where other medications have failed. ^{2 11 12 13 14}

Research Team

Devang Sanghavi, MBBS, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

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

I have experienced changes in my thinking or awareness.

Timeline

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Intravenous ketamine therapy in a patient with a treatment-resistant major depression. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Ketamine: A Review for Clinicians. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Side-effects associated with ketamine use in depression: a systematic review. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Subcutaneous Ketamine in Depression: A Systematic Review. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. [2013]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Repeated Administration of Parenteral Ketamine for Depression. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

Use of ketamine and esketamine for depression: an overview of systematic reviews with meta-analyses. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Repeated intranasal ketamine for treatment-resistant depression - the way to go? Results from a pilot randomised controlled trial. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Long-Term Ketamine Self-Injections in Major Depressive Disorder: Focus on Tolerance in Ketamine's Antidepressant Response and the Development of Ketamine Addiction. [2022]

13. New Zealand pubmed.ncbi.nlm.nih.gov

Ketamine and depression: a narrative review. [2020]

14. England pubmed.ncbi.nlm.nih.gov

Intravenous ketamine infusion for a patient with treatment-resistant major depression: a 10-month follow-up. [2018]