Nebulized Ketamine for Depression

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Theresa Jacob, PhD, MPH

Must not be taking: Lithium, Lamotrigine, Opioids, others

Disqualifiers: Bipolar, Psychotic disorders, Hypertension, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a double blind active placebo controlled clinical trial for individuals within an inpatient setting with moderate to severe depression. The purpose of this study is to assess if nebulized ketamine can reduce depressive symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are on lithium, lamotrigine, or more than two medications for high blood pressure. You also cannot have used opioids within 24 hours before the trial.

Is nebulized ketamine safe for humans?

Research on ketamine, often used for depression, shows that while it can have side effects, they are usually temporary and manageable. However, there are reports of serious but rare side effects like apnea (temporary stopping of breathing) during treatment, so careful monitoring is recommended. ^{1 2 3 4 5}

How is nebulized ketamine different from other depression drugs?

Nebulized ketamine is unique because it is administered through inhalation, which is different from the more common intravenous or oral routes used for ketamine in treating depression. This method could offer a more convenient and potentially faster-acting alternative for patients. ^{1 6 7 8 9}

Research Team

Eligibility Criteria

This trial is for inpatients with moderate to severe depression. Specific eligibility criteria are not provided, but typically participants must meet diagnostic criteria for Major Depressive Disorder and be able to give informed consent.

Inclusion Criteria

I am 18 or older with a severe depression score.

Structured Clinical Interview for DSM-5 (SCID-5) will be performed to confirm MDD diagnosis

I have been diagnosed with moderate to severe depression.

Exclusion Criteria

I am allergic to ketamine.

Recent or current homicidal ideation with an intent to act

Acutely intoxicated patients will also be excluded

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive nebulized ketamine or midazolam as an active placebo, with dosing days requiring in-person visits and monitoring for a minimum of two hours.

8-10 days

4-5 visits (in-person for dosing, otherwise remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in depressive symptoms and side effects.

1-2 weeks

Treatment Details

Interventions

• Nebulized Ketamine (NMDA Receptor Antagonist)

Trial Overview The study is testing if nebulized ketamine can alleviate symptoms of depression. It's a double-blind trial, meaning neither the patients nor the researchers know who receives ketamine or a placebo (inactive substance).

Participant Groups

Group I: Nebulized Ketamine Experimental Treatment 1 Intervention

Ketamine dosage calculated by body weight at 1.5mg/kg

Group II: Nebulized Midazolam Active Control 1 Intervention

Midazolam used as active placebo. Dosage calculated by body weight at 0.03mg/kg

Who Is Running the Clinical Trial?

Theresa Jacob, PhD, MPH

Lead Sponsor

Trials

1

Recruited

40+

Findings from Research

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]

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]

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]

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]

Ketamine shows promise as a treatment for treatment-resistant depression (TRD), but its use can lead to common adverse events, which are usually temporary.

A case of apnea during a slow sub-anesthetic infusion of ketamine highlights a rare but serious potential side effect, emphasizing the need for careful monitoring and management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. Gómez-Revuelta, M., Fernández-Rodríguez, M., Boada-Antón, L., et al.[2021]

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]

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]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

A retrospective analysis of 2758 patients treated with ketamine intravenous therapy (KIT) across ten clinics showed significant reductions in both depression and anxiety symptoms after treatment, with effect sizes indicating strong efficacy (Cohen's d = -1.17 for anxiety and d = -1.56 for depression).

Patients receiving KIT experienced greater reductions in depression symptoms compared to those who were not treated with KIT or who started standard antidepressant therapy, with sustained symptom relief observed for up to a year after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis. Hietamies, TM., McInnes, LA., Klise, AJ., et al.[2023]

References

1. 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]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. Netherlands pubmed.ncbi.nlm.nih.gov

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

7. England 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. [2023]

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

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis. [2023]