Ketamine for Dissociative Symptoms

Overseen By Karl Deisseroth, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Disqualifiers: Psychotic, Bipolar, Pregnant, 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: 1

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to understand how ketamine brings about dissociative symptoms.

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

The trial information does not specify if you need to stop your current medications, so it's best to ask the study team for guidance.

What evidence supports the effectiveness of the drug ketamine for dissociative symptoms?

Research shows that ketamine can quickly improve symptoms of depression, including treatment-resistant cases, and is effective when used with psychotherapy for reducing depression and anxiety. Its rapid effects and safety profile make it a promising option for various mental health conditions. ^{1 2 3 4 5}

Is ketamine generally safe for humans?

Ketamine is generally considered safe for humans, with common side effects including a sense of detachment from reality and increased blood pressure. It has an excellent safety profile, making it a preferred choice for pediatric sedation and veterinary medicine, and even in cases of recreational overdose, serious harm is rare. ^{3 6 7 8 9}

How does ketamine differ from other drugs for dissociative symptoms?

Ketamine is unique because it works quickly and can cause dissociative symptoms, which are linked to its effectiveness in treating depression and anxiety. Unlike other treatments, ketamine is administered intravenously and acts as an NMDA-receptor antagonist, which is different from traditional antidepressants. ^{10 11 12 13 14}

Research Team

Karl Deisseroth, MD, PhD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults over 18 with epilepsy who are in the Stanford Epilepsy Monitoring Unit. It's not suitable for those who can't communicate in English, are pregnant or nursing, have had bad reactions to ketamine before, or have a history of psychotic or bipolar disorders.

Inclusion Criteria

I am older than 18 years.

I am a patient in the Stanford Epilepsy Monitoring Unit.

Exclusion Criteria

I have had a bad reaction to ketamine before.

Pregnant or nursing females

You have been diagnosed with a serious mental health condition like schizophrenia or bipolar disorder at any point in your life.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of 0.5mg/kg of ketamine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for dissociative events and safety after ketamine infusion

1 week

Treatment Details

Interventions

• Ketamine

Trial Overview The study focuses on understanding how ketamine may cause dissociative symptoms among epilepsy patients. Participants will receive ketamine under controlled conditions while their responses and experiences are closely monitored.

Participant Groups

Group I: Ketamine Experimental Treatment 1 Intervention

Study participants will receive 0.5mg/kg of ketamine - one single infusion

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

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]

Ketamine Assisted Psychotherapy (KAP) is an effective treatment for reducing depression and anxiety, particularly in older patients and those with severe symptoms, based on data from 235 patients.

Unlike traditional intravenous ketamine treatments that view its psychedelic effects as side effects, KAP utilizes these effects in a therapeutic context, making it suitable for office and supervised at-home use due to ketamine's proven safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. Dore, J., Turnipseed, B., Dwyer, S., et al.[2020]

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]

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]

In a study involving five participants with eating disorders and comorbid mood and anxiety disorders, weekly group-based ketamine-assisted psychotherapy (G-KAP) over 4 weeks led to significant improvements in depression and anxiety symptoms for most participants, with four showing notable reductions in depression scores and two in anxiety scores.

The ketamine treatment was well tolerated with no serious adverse events reported, indicating its safety and feasibility as an adjunct therapy in intensive residential eating disorder treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders. Robison, R., Lafrance, A., Brendle, M., et al.[2022]

Ketamine is considered very safe, making it a preferred choice for sedation in children and in veterinary medicine, with low rates of serious complications from intentional overdose.

Most risks associated with ketamine use arise from accidents during its recreational use, particularly due to the potential for vomiting and aspiration in deeply sedated individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine as a street drug. Stewart, CE.[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]

An extended release oral ketamine tablet was found to be safe and well tolerated in a study of seven patients with treatment-resistant depression/anxiety, with no significant changes in vital signs and only one brief report of dissociation.

All patients experienced over 50% improvements in mood ratings over 96 hours, suggesting that while the onset of mood improvement is slightly delayed compared to injectable forms, this oral formulation could be a promising option for treating resistant depression and anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. Glue, P., Medlicott, NJ., Neehoff, S., 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]

In a study of 126 treatment-resistant patients with major depressive disorder or bipolar disorder, ketamine infusion led to significant antidepressant effects, with the depersonalization dissociative symptom being positively associated with improvement in depression scores.

The study suggests that the depersonalization aspect of dissociation may share neurobiological mechanisms with the antidepressant response to ketamine, indicating a potential link between these experiences and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression. Niciu, MJ., Shovestul, BJ., Jaso, BA., et al.[2019]

In a study of 18 patients with treatment-resistant anxiety, ketamine was found to increase dissociative symptoms in a dose-dependent manner, while midazolam did not affect dissociation ratings.

The Clinician-Administered Dissociative States Scale (CADSS) demonstrated high internal consistency (Cronbach alpha of 0.937) for assessing ketamine-induced dissociation, making it a reliable tool for clinical trials, although it may not fully capture all dissociative symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ketamine dose on self-rated dissociation in patients with treatment refractory anxiety disorders. Castle, C., Gray, A., Neehoff, S., et al.[2018]

A single intravenous dose of ketamine significantly improved depressive symptoms in 68 participants with treatment-resistant major depressive disorder or bipolar depression, showing notable effects at Day 1 and Day 3 post-infusion.

The treatment was more effective for typical/melancholic symptoms compared to atypical symptoms, indicating that ketamine may have a preferential impact on certain types of depressive symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of ketamine on typical and atypical depressive symptoms. Park, LT., Luckenbaugh, DA., Pennybaker, SJ., et al.[2023]

In a study involving 61 adults with treatment-resistant depression, both ketamine and esketamine were found to induce dissociative symptoms, with over 30% of participants experiencing significant dissociation, but these effects were not classified as serious adverse events.

The research indicated that individuals with higher levels of trait dissociation were more likely to experience induced dissociation when treated with ketamine or esketamine, suggesting that screening for trait dissociation could help identify patients at risk and inform counseling about potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trait dissociation as a predictor of induced dissociation by ketamine or esketamine in treatment-resistant depression: Secondary analysis from a randomized controlled trial. Mello, RP., Echegaray, MVF., Jesus-Nunes, AP., et al.[2021]

Chronic administration of low doses of ketamine (5 mg/kg) in adult Wistar rats for 14 days led to impaired performance in memory tasks, indicating potential cognitive deficits associated with sub-anesthetic use.

In contrast, higher doses (10 mg/kg) did not produce the same negative effects, suggesting that lower doses of ketamine may disrupt spatial memory and habituation, while higher doses may not have these cognitive impacts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impaired spatial memory after ketamine administration in chronic low doses. Venâncio, C., Magalhães, A., Antunes, L., et al.[2021]

References

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

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

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

Ketamine Assisted Psychotherapy (KAP): Patient Demographics, Clinical Data and Outcomes in Three Large Practices Administering Ketamine with Psychotherapy. [2020]

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

Influence of formulation and route of administration on ketamine's safety and tolerability: systematic review. [2021]

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

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

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

A case series of group-based ketamine-assisted psychotherapy for patients in residential treatment for eating disorders with comorbid depression and anxiety disorders. [2022]

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

Ketamine as a street drug. [2019]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

Safety and efficacy of extended release ketamine tablets in patients with treatment-resistant depression and anxiety: open label pilot study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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

10. Netherlands pubmed.ncbi.nlm.nih.gov

Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression. [2019]

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

Effect of ketamine dose on self-rated dissociation in patients with treatment refractory anxiety disorders. [2018]

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

The effects of ketamine on typical and atypical depressive symptoms. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Trait dissociation as a predictor of induced dissociation by ketamine or esketamine in treatment-resistant depression: Secondary analysis from a randomized controlled trial. [2021]

14. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Impaired spatial memory after ketamine administration in chronic low doses. [2021]