Ketamine + Virtual Reality for Depression

(TREASURE Trial)

Overseen By Fahad Alam, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sunnybrook Health Sciences Centre

Must be taking: IV ketamine

Must not be taking: Non-prescribed substances

Disqualifiers: Psychosis, Substance misuse, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

31 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must not have used non-prescribed substances or alcohol within 48 hours before treatment.

What data supports the effectiveness of the drug ketamine for depression?

Research shows that ketamine can quickly reduce symptoms of depression, especially in people who haven't responded to other treatments. It has been effective in improving mood and reducing negative beliefs that contribute to depression. ^{1 2 3 4 5}

Is the combination of ketamine and virtual reality safe for treating depression?

Research shows that ketamine, when used for depression, can have side effects like changes in mood, heart issues, and other physical effects. However, there is limited information on the long-term safety of repeated use, and more studies are needed to fully understand its safety profile. ^{6 7 8 9 10}

How is the drug ketamine unique for treating depression?

Ketamine is unique for treating depression because it acts quickly to relieve symptoms, unlike traditional antidepressants that can take weeks to work. It can be administered in various ways, including orally, intravenously, and intranasally, offering flexibility in treatment options. ^{11 12 13 14 15}

What is the purpose of this trial?

Depression is a common condition, with serious negative effects on the health and quality of life of those affected. While there are currently various medications which attempt to treat depression, they often take a long time to begin to work and do not work at all for many people. There is therefore a need for new treatments which work quickly and effectively. One such medication is called ketamine. Studies have shown that ketamine can treat symptoms of depression quickly. This quick action sets ketamine apart from many antidepressants that take weeks to show noticeable effects. One way that it may do this is by creating a transient sense or feeling of being separated from reality, such as seeing or hearing things that are not really there. Another way to create these same feelings is with virtual reality (VR), where a person can feel as though they are entering a 3-dimensional virtual computer-generated world by wearing a special headset or goggles with a computer inside. In this study, all participants will receive standard ketamine treatments for depression. Half of the participants will also use a VR headset while receiving the ketamine treatments to see if ketamine and VR acting together provide a better treatment for symptoms of depression than ketamine alone. This is a small pilot trial. The main purpose of this trial is to learn if it is possible to run a larger clinical trial comparing "ketamine and VR" with "ketamine alone", for adults with treatment-resistant depression. The researchers will study this by seeing how many participants take part in the study within 1-2 years, and how many complete the study treatments and tests. The researchers will also compare the two study groups to see if "ketamine and VR" provide a better treatment for symptoms of depression than "ketamine alone".

Eligibility Criteria

This trial is for adults with treatment-resistant depression, meaning their condition hasn't improved after trying other medications. Participants must be willing to undergo ketamine treatments and use a VR headset if assigned to that group.

Inclusion Criteria

I am mentally alert and can engage with and respond to immersive content.

My psychiatrist has approved me for outpatient ketamine treatment.

I am prescribed IV ketamine by my doctor and need at least 4 treatments per course.

Exclusion Criteria

Using non-prescribed substance (e.g., cannabis) or alcohol use within the preceding 48 hours of treatment

Previous ketamine use

Inability to communicate with the study team

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I - VR Software Development

Participants provide feedback to develop the VR software for the study population

Not specified

Phase II - Treatment

Participants receive 4 ketamine treatments over 2 weeks, with half using VR concurrently

2 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

1, 2, 3-week and 1 and 3 month follow-ups

Treatment Details

Interventions

• Ketamine
• Oculus VR headset

Trial Overview The study is testing whether combining ketamine treatments with immersive virtual reality (using an Oculus VR headset) can more effectively treat symptoms of depression compared to ketamine alone. It's a pilot trial aimed at setting the stage for larger studies.

Participant Groups

Group I: VR-Ketamine (VR-K) Experimental Treatment 2 Interventions

Participants will receive a standard course of ketamine treatment. At the onset of each ketamine therapy session, participants will be provided with an Oculus VR headset, and will be immersed in a tailor-made virtual environment of positive outdoor scenes.

Group II: Ketamine alone Active Control 1 Intervention

Participants will receive a standard course of ketamine treatment.

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

In a study involving 56 participants, including 26 patients with treatment-resistant depression (TRD), ketamine infusions were found to significantly enhance belief updating after receiving good news compared to bad news, indicating a cognitive effect that may contribute to its rapid antidepressant response.

The study revealed that ketamine treatment led to asymmetrical learning rates, where patients updated their beliefs more positively after good news, which was linked to early improvements in depression symptoms, suggesting potential for integrating ketamine with psychotherapy for mood disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant Depression. Bottemanne, H., Morlaas, O., Claret, A., 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]

In a systematic review of 93 studies involving 3756 participants receiving sub-anesthetic doses of ketamine for psychiatric disorders, only four serious adverse medical events (MSAEs) were reported, resulting in an incidence of approximately 0.1%, indicating a very low risk of serious complications.

No serious cardiac events or deaths were observed, and most studies effectively screened out high-risk patients, suggesting that with proper medical screening, ketamine can be administered safely for psychiatric treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. Hovda, N., Gerrish, W., Frizzell, W., et al.[2023]

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]

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]

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 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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Patients' recovery and non-recovery narratives after intravenous ketamine for treatment-resistant depression. [2023]

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

Evaluation of Early Ketamine Effects on Belief-Updating Biases in Patients With Treatment-Resistant 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. Netherlands pubmed.ncbi.nlm.nih.gov

A 12-month naturalistic observation of three patients receiving repeat intravenous ketamine infusions for their treatment-resistant depression. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The effect of ketamine on cognition, anxiety, and social functioning in adults with psychiatric disorders: A systematic review and meta-analysis. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A systematic review of the incidence of medical serious adverse events in sub-anesthetic ketamine treatment of psychiatric disorders. [2023]

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

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

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

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

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

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

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

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

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

12. 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]

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

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

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

Low-dose ketamine infusion in treatment-resistant double depression: Revisiting the adjunctive ketamine study of Taiwanese patients with treatment-resistant depression. [2022]

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

KETAMINE FOR TREATMENT-RESISTANT UNIPOLAR AND BIPOLAR MAJOR DEPRESSION: CRITICAL REVIEW AND IMPLICATIONS FOR CLINICAL PRACTICE. [2018]