Ketamine for Depression

Recruiting at 1 trial location

Overseen By Nicholas Murphy

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must be taking: Psychotropic medications

Must not be taking: NMDA, AMPA, Opioids, others

Disqualifiers: Psychotic disorders, Major medical problems, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 8

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how ketamine, an anesthetic, affects depression by examining changes in brain activity and their link to treatment outcomes. Participants will receive either a ketamine or saline infusion to determine if ketamine can reduce depressive symptoms. This study targets individuals with major depressive disorder, particularly those who have not found relief from at least two antidepressant treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

Participants must be on a stable dose of their current psychotropic medications for at least 4 weeks before the study. However, certain medications, like those affecting specific brain receptors, benzodiazepines over 6mg/day, prescription opioids, and some dietary supplements, must be stopped before the study.

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

Research has shown that ketamine is generally safe and effective for treating depression, even when other treatments have failed. In previous studies, some participants experienced temporary side effects from ketamine, but these typically resolved on their own. One study found that ketamine quickly and significantly reduced depression symptoms, with effects lasting up to a month after treatment. Additionally, repeated ketamine use did not cause any major safety issues. Overall, ketamine appears to be a promising and safe option for individuals dealing with depression. ^{1 2 3 4 5}

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

Most treatments for depression, like SSRIs and SNRIs, take weeks to show effectiveness, but ketamine has the potential to deliver results in just days. Researchers are excited about ketamine because it works differently from traditional antidepressants. It targets the NMDA receptors in the brain, which could rapidly improve mood and symptoms. This unique mechanism offers hope, especially for those with treatment-resistant depression, who haven't found relief with other medications.

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

Research has shown that ketamine can quickly and effectively reduce depression symptoms. One study found that these effects appeared immediately after taking ketamine and could last up to a month. In this trial, participants with treatment-resistant depression will receive multiple ketamine infusions, while those with major depressive disorder will receive a single infusion. Specifically, individuals whose depression hasn't improved with other treatments reported a better quality of life after using ketamine. However, some studies suggest that the antidepressant effects of ketamine might not last long. While it works fast, its benefits can be short-lived, especially for those with long-term treatment-resistant depression. Overall, ketamine is considered a promising option for people who haven't found relief with other treatments. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with treatment-resistant depression, including those diagnosed with Major Depressive Disorder. Healthy subjects are also included to provide a comparison group. Participants must meet specific criteria not detailed here.

Inclusion Criteria

Level of understanding sufficient to agree to all tests and examinations required by the protocol

I have been diagnosed with major depression for at least 4 weeks.

My mental health medication doses have been stable for at least 4 weeks.

Exclusion Criteria

Patients at serious and imminent risk of suicide and not suitable for an outpatient study

Body mass index (BMI) >=40 kg/m2

Dietary supplements affecting central nervous system (CNS) function will be discontinued before the study start

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive ketamine infusions to assess gamma potentiation as a prognostic marker

4 weeks

8 infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Study exit visit (up to a month after infusion)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study tests if brain wave patterns (gamma oscillations) can predict how well patients respond to ketamine therapy over four weeks. It involves comparing the effects of saline (a placebo) and ketamine on these brain waves in people with depression.

How Is the Trial Designed?

Group I: Healthy Controls Active Control 2 Interventions

Healthy controls will receive one saline and ketamine infusion.

Group II: Treatment Resistant Depression Active Control 2 Interventions

Treatment Resistant Depression participants will receive 8 ketamine infusions where their first and fourth infusions are a saline and ketamine infusion.

Group III: Major Depressive Disorder Active Control 2 Interventions

Major Depressive Disorder participants will receive one saline and ketamine infusion.

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

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]

A review of 41 treatment arms from 21 studies found that ketamine formulations that maximize first pass metabolism and delay the time to peak concentration (Tmax) are associated with better safety and tolerability, particularly in reducing side effects like dissociation and increased blood pressure.

The study revealed strong correlations between the ketamine:norketamine ratio and both dissociation ratings and blood pressure changes, suggesting that careful formulation can help minimize adverse effects while maintaining the antidepressant efficacy of ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. Glue, P., Russell, B., Medlicott, NJ.[2021]

There is currently no standardized safety monitoring protocol for off-label use of generic ketamine, and safety monitoring for intranasal esketamine varies by jurisdiction, leading to potential gaps in patient safety.

The Ketamine Side Effect Tool (KSET) is recommended as a comprehensive tool for monitoring both acute and long-term side effects of ketamine and esketamine treatments, addressing the lack of agreed frameworks for safety monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. Bayes, A., Short, B., Zarate, CA., 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]

Intravenous ketamine has been shown to be safe and effective in rapidly reducing depressive symptoms, including suicidal thoughts, in patients with treatment-resistant unipolar or bipolar depression, based on five controlled studies and additional open-label studies.

While ketamine shows promise as a short-term antidepressant therapy, further research is needed to assess its long-term safety and effectiveness, as well as the efficacy of alternative administration routes like oral or intranasal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for the treatment of depression. Howland, RH.[2022]

Racemic ketamine and its derivative, S-ketamine, have been shown to provide rapid relief from depressive symptoms, with effects lasting approximately 2-3 weeks after treatment, based on multiple clinical trials.

Further research is needed to optimize dosing strategies, especially for specific populations like obese individuals, and to monitor long-term safety regarding cognitive and organ system effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key considerations for the use of ketamine and esketamine for the treatment of depression: focusing on administration, safety, and tolerability. Kritzer, MD., Pae, CU., Masand, PS.[2023]

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]

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]

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]

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 Phase I study involving 32 patients showed that esketamine (0.5 mg/kg) is generally safe and well-tolerated for use in painless gastroscopy, with no serious adverse events reported.

Esketamine resulted in a shorter recovery time compared to racemic ketamine (9 minutes vs. 13 minutes), making it a potentially more efficient option for anesthesia without gender differences affecting its pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study. Wang, J., Huang, J., Yang, S., et al.[2022]

In a study involving 156 participants with suicidal ideation, ketamine treatment led to a significantly higher rate of full remission of suicidal thoughts at day 3 compared to placebo, with 63% of those receiving ketamine achieving remission versus 31.6% in the placebo group.

The study found that ketamine was safe in the short term, with limited side effects and no occurrences of manic or psychotic symptoms, suggesting it could be a rapid and effective option for acute care in suicidal patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial. Abbar, M., Demattei, C., El-Hage, W., et al.[2022]

A 65-year-old male cancer patient experienced significant improvement in depression symptoms and achieved remission within 7 days after receiving subcutaneous esketamine, indicating its rapid antidepressant effect.

Subcutaneous administration of esketamine appears to be a safe and effective option for managing both pain and depression in palliative care, suggesting it could be a valuable alternative to traditional intravenous methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated subcutaneous esketamine administration for depressive symptoms and pain relief in a terminally ill cancer patient: A case report. Barbosa, MG., Delfino, RS., Sarin, LM., et al.[2021]

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/abs/pii/S0165032725009449

Economic evaluation of subcutaneous ketamine injections ... Ketamine for treatment resistant depression showed significant utility gains. Quality-adjusted life years were significantly higher in the ketamine group.

3. 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 as a rapid intervention for major depression, and to investigate ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602384/

Ketamine for Adults With Treatment-Resistant Depression or ... A 2022 CADTH report 24 on the use of ketamine for PTSD or TRD found insufficient evidence to provide definitive conclusions about its clinical effectiveness.

5. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-024-06203-2

Ketamine and chronic treatment-resistant depression Ketamine has shown a rapid but short-lived antidepressant effect in several studies involving TRD patients with different demographic and clinical profiles.

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

Pharmacokinetics, Safety, and Tolerability of (R)-Ketamine ... The adverse events of (R)-ketamine hydrochloride injection were temporary and recovered spontaneously without treatment. Conclusions: In summary ...

7. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2022/RC1420-Ketamine-for-treatment-resistant-depression-and-PTSD.pdf

Ketamine for Adults With Treatment-Resistant Depression ... A small retrospective chart review study showed that repeated administration of intramuscular ketamine had no significant differences in the improvement of ...

8. 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 ...

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

Ketamine for the Treatment of Depression and Other ... Included articles were qualitatively analyzed to determine anti-depressant safety, tolerability, efficacy, dose range, anti-suicide effects, time to effect, and ...