Ketamine + DBT for Treatment-Resistant Depression

(KET-RO Trial)

No longer recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for young adults with treatment-resistant depression, a severe form that hasn't improved with standard treatments. Researchers are testing a combination of ketamine infusions and Radically Open Dialectical Behavior Therapy (RO DBT) to assess its safety and effectiveness. This trial suits individuals who have experienced multiple episodes of depression and haven't responded to at least two different antidepressant treatments. Participants should be able to attend in-person sessions and speak English. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

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.

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

Research has shown that ketamine infusions are generally safe and well-tolerated for people with treatment-resistant depression (TRD). Studies have found that while ketamine can cause side effects, they are usually mild and temporary. Common side effects include dizziness, nausea, and changes in blood pressure. However, limited information exists on long-term safety, so potential risks like tolerance or withdrawal should be monitored.

Radically Open Dialectical Behavior Therapy (RO DBT) has proven effective for chronic depression. Although specific data on its side effects is limited, therapy in general is considered safe. RO DBT aims to improve emotional openness and social connections, which can help with depression.

In summary, both ketamine infusions and RO DBT have shown promise for safety in treating depression, but monitoring and guidance from healthcare professionals remain important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ketamine infusion and Radically Open Dialectical Behavior Therapy (RO DBT) for treatment-resistant depression because these treatments work in unique ways compared to traditional options. Ketamine, typically used as an anesthetic, is gaining attention for its rapid antidepressant effects, often showing results in just hours or days, unlike standard antidepressants, which can take weeks. Meanwhile, RO DBT focuses on treating disorders linked to excessive self-control, offering a fresh therapeutic angle for patients who haven't responded well to other psychological therapies. This dual approach targets both the brain's chemistry and emotional regulation, giving hope to those who haven't found relief with conventional treatments.

What evidence suggests that this trial's treatments could be effective for Treatment-Resistant Depression?

Research has shown that ketamine infusions, one of the treatments in this trial, can significantly help people with depression. In some studies, about 55% of patients with treatment-resistant depression improved after receiving ketamine. However, effects can vary, and symptoms may return within a month after stopping treatment.

Radically Open Dialectical Behavior Therapy (RO DBT), another treatment option in this trial, has also shown promise for treating depression. Clinical studies found that people who received RO DBT experienced a significant reduction in depression symptoms compared to those who received standard treatment. Some reports indicate that up to 71% of people might fully recover from long-term depression with RO DBT. These findings suggest that both ketamine and RO DBT could be effective for individuals whose depression hasn't improved with other treatments. ^{5 6 7 8 9}

Who Is on the Research Team?

Kirsten Gilbert, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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/abs/pii/S0165178125003397

Real World Effectiveness of Maintenance Ketamine ...

Compared to both control groups, depression scores in the ketamine and ASAT groups decreased after treatment with ketamine and remained low with ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36112599/

Clinical Effectiveness of Intravenous Racemic Ketamine ...

Based on PHQ-9 self-report data, within 6 weeks of infusion initiation, a 50% response rate and 20% remission rate for depressive symptoms were ...

4.

bmcpsychiatry.biomedcentral.com

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

Ketamine and chronic treatment-resistant depression

Only one patient (5.56%) achieved remission at the end of the infusion phase. All but one ketamine responders relapsed within one month after ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165178124001501

IV low dose ketamine infusions for treatment resistant ...

54.93% of patients responded to the treatment, 78.26% experienced transient and mild side effects, and 11.27% of dropped out of the treatment. Multivariate ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/25271445/

Ketamine safety and tolerability in clinical trials for treatment ...

Conclusions: In this relatively large group of patients with TRD, ketamine was safe and well tolerated. Further research investigating the safety of ketamine in ...

7.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S016517812400619X

Safety outcomes of ketamine for treatment-resistant ...

The Ketamine Side Effect Tool (KSET) was developed to provide a systematised safety monitoring tool for ketamine therapy in psychiatry.

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6236511/

On the safety of repeated ketamine infusions for ...

In this review, we will discuss the safety of repeated treatments with ketamine for patients with treatment-resistant depression (TRD).

9.

va.gov

va.gov/formularyadvisor/DOC_PDF/CRE_Ketamine_Infusion_for_Treatment_Resistant_Depression_Rev_Jul_2022.pdf

Ketamine Infusion for Treatment Resistant Depression and ...

In the interest of patient safety, ketamine should be tapered and discontinued. At present this time frame is undefined and will need to be individualized.