Ketamine + DBT for Treatment-Resistant Depression

(KET-RO Trial)

Overseen By Teresa Perryman, BA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Washington University School of Medicine

Must be taking: Antidepressants

Must not be taking: Naltrexone, Memantine

Disqualifiers: Neurological condition, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot study will assess the safety and feasibility of intravenous (IV) ketamine combined with RO DBT in young adults with Treatment-Resistant Depression (TRD). In addition, this study will develop and utilize innovative methodological approaches to demonstrate the feasibility of precision medicine with this type of therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that medication treatment may continue. However, you cannot use naltrexone, memantine, or any medication that is considered unsafe with ketamine.

What data supports the effectiveness of the drug ketamine for treatment-resistant depression?

Research shows that intravenous ketamine can quickly reduce symptoms in people with treatment-resistant depression, with many patients experiencing significant improvement after repeated infusions. The treatment is generally safe, with only mild and temporary side effects reported. ^{1 2 3 4 5}

Is ketamine safe for treating treatment-resistant depression?

Research shows that ketamine, whether given through an IV or as a shot, is generally safe for people with treatment-resistant depression. Most side effects are mild and temporary, but more studies are needed to understand its long-term safety. ^{1 4 6 7 8}

How is the drug ketamine combined with DBT different for treatment-resistant depression?

The combination of ketamine infusions with Dialectical Behavior Therapy (DBT) is unique because ketamine acts rapidly to relieve depressive symptoms, while DBT provides long-term skills to manage emotions and behaviors. This dual approach targets both immediate symptom relief and sustainable mental health improvements, which is different from traditional antidepressants that often take weeks to show effects. ^{1 9 10 11 12}

Research Team

Kirsten Gilbert, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for young adults aged 18-25 with Treatment-Resistant Depression, having had at least two major depressive episodes and no response to different antidepressant treatments. Participants must speak English, be able to attend sessions in person, and not have any current psychosis or significant neurological conditions.

Inclusion Criteria

You tend to agree more with words that show overcontrol rather than undercontrol on a word pairs checklist.

I have severe depression that hasn't improved with treatment.

My depression hasn't improved after trying two different antidepressants.

Exclusion Criteria

Not be pregnant or at risk of becoming pregnant

Medical conditions or medication usage that in the judgement of the investigators puts the patient at unreasonable safety risk

Current or recent substance use disorder, actively suicidal or homicidal (e.g., requires hospitalization)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous (IV) ketamine combined with RO DBT for Treatment-Resistant Depression

4 weeks

Daily following ketamine and therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 months

Treatment Details

Interventions

• Ketamine Infusion
• RO DBT

Trial Overview The study tests the safety and potential effectiveness of Ketamine Infusion combined with RO DBT (a type of therapy) on individuals who haven't responded well to standard depression treatments. It aims to explore precision medicine approaches for treating persistent depression.

Participant Groups

Group I: Radically Open Dialectical Behavior Therapy (RO DBT) Experimental Treatment 1 Intervention

Group II: Ketamine Infusion Experimental Treatment 1 Intervention

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

Approved in United States as Ketalar for:

• Anesthesia
• Pain management
• Depression (off-label)

Approved in European Union as Ketanest for:

• Anesthesia
• Pain management

Approved in Canada as Ketamine for:

• Anesthesia
• Pain management

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

In a study of 201 adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD), intravenous (IV) ketamine significantly reduced symptoms of anxiety, irritability, and agitation in those with mixed features, indicating its effectiveness in treating these symptoms.

Participants with anxiety, irritability, and agitation (AIA) experienced greater reductions in overall depressive symptoms and suicidal ideation compared to those without AIA, suggesting that IV ketamine could be a rapid treatment option for adults with mood disorders presenting with mixed features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. McIntyre, RS., Lipsitz, O., Rodrigues, NB., et al.[2021]

In a study of 53 older adults with treatment-resistant depression, repeated intravenous (IV) ketamine infusions led to significant reductions in depressive symptoms, with 27% of participants showing a response and 10% achieving remission after 4 infusions.

While ketamine was effective, 69% of participants experienced transient hypertension during treatment, highlighting the need for monitoring and potential intervention for this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Real-World Effectiveness of Intravenous Ketamine in Older Adults With Treatment-Resistant Depression: A Case Series. Lipsitz, O., Di Vincenzo, JD., Rodrigues, NB., et al.[2021]

In a study of 203 patients with treatment-resistant depression receiving repeat-dose IV ketamine, the treatment was found to be safe and well-tolerated, with less than 5% of patients withdrawing due to tolerability issues.

While transient hypertension occurred in 44.3% of patients during infusion, and some required medication to manage it, no serious psychiatric side effects like psychosis or new onset suicidality were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence. Rodrigues, NB., McIntyre, RS., Lipsitz, O., et al.[2021]

Intravenous ketamine has shown rapid antidepressant effects in patients with treatment-resistant major depressive disorder (MDD), with several studies reporting moderate to large effect sizes on depression scales.

Despite its promising rapid action and relatively well-tolerated side effects, the long-term sustainability of ketamine's antidepressant effects remains uncertain, indicating a need for further research before it can be widely recommended as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous ketamine for treatment-resistant major depressive disorder. Covvey, JR., Crawford, AN., Lowe, DK.[2013]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Repeated Series of Ketamine Infusions in Patients With Treatment-Resistant Depression: Presentation of Five Cases. [2021]

2. Denmark pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Real-World Effectiveness of Intravenous Ketamine in Older Adults With Treatment-Resistant Depression: A Case Series. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study. [2020]

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

Repeated, low-dose oral esketamine in patients with treatment-resistant depression: pilot study. [2022]

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

Pilot Randomized Controlled Trial of Titrated Subcutaneous Ketamine in Older Patients with Treatment-Resistant Depression. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of IV ketamine in adults with major depressive or bipolar disorder: results from the Canadian rapid treatment center of excellence. [2021]

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

Intravenous ketamine for treatment-resistant major depressive disorder. [2013]

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

The effectiveness of repeated intravenous ketamine on depressive symptoms, suicidal ideation and functional disability in adults with major depressive disorder and bipolar disorder: Results from the Canadian Rapid Treatment Center of Excellence. [2021]

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

Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Repeated subcutaneous racemic ketamine in treatment-resistant depression: case series. [2023]

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

Augmentation Therapy With Serial Intravenous Ketamine Over 18 Months in a Patient With Treatment Resistant Depression. [2015]