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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how ketamine affects dissociative symptoms, which involve feelings of detachment from reality. The aim is to understand the specific effects of ketamine, a drug sometimes used for treatment-resistant depression and other conditions. Participants will receive a single infusion of ketamine to observe its impact. Those in the Stanford Epilepsy Monitoring Unit who have not experienced adverse reactions to ketamine may qualify for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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.

Is there any evidence suggesting that ketamine is likely to be safe for humans?

Research has shown that ketamine is generally safe as an anesthetic. In medical settings, it induces unconsciousness during surgery. Ketamine creates a unique state called "dissociative anesthesia," where patients feel disconnected from their surroundings.

Studies have found that common side effects include increased saliva, double vision, and difficulty moving. These effects usually don't last long. Typically, the dose for anesthesia is about 2 mg per kilogram of body weight. However, this study uses a much lower dose of 0.5 mg/kg, which may reduce the risk of side effects.

Ketamine's long history in medicine supports its general safety. However, individual reactions can vary. Discuss potential risks with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for dissociative symptoms, which often involve traditional antidepressants or psychotherapy, ketamine offers a rapid-acting alternative. Ketamine works differently by acting on the brain's glutamate system, potentially providing quick relief of symptoms. Researchers are excited because ketamine's unique mechanism could offer faster results, sometimes within hours, compared to the weeks or months it usually takes for conventional treatments to take effect. Additionally, ketamine's single-infusion administration could make it a convenient option for patients seeking rapid relief.

What evidence suggests that ketamine might be an effective treatment for dissociative symptoms?

Research has shown that ketamine can cause feelings of detachment from reality, known as dissociative effects. Some studies have explored how these effects might relate to ketamine's ability to reduce depression and suicidal thoughts. One study found that these dissociative effects might predict a stronger and longer-lasting relief from depression. However, the exact connection between ketamine's dissociative effects and its benefits for depression remains unclear. In this trial, participants will receive a single infusion of ketamine to further investigate its role in treating mental health conditions, including its dissociative effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Karl Deisseroth, MD, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36799961/

The Relationship Between Acute Dissociative Effects ... The current data do not show a relationship between acute dissociative effects and antidepressant response to ketamine in pediatric patients with TRD.

2. nature.com nature.com/articles/s41467-020-20190-4

The role of dissociation in ketamine's antidepressant effects This perspective examines the relationship between dissociative effects and acute and longer-lasting antidepressant response to ketamine and other N-methyl-D- ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022395621002831

Trait dissociation as a predictor of induced ... Trait dissociation values were similar among ketamine and esketamine groups. · More than 30% of patients in both groups had high levels of trait dissociation.

4. academic.oup.com academic.oup.com/ijnp/article/27/4/pyae017/7640766

Acute Dissociation and Ketamine's Antidepressant and Anti ... This paper explores the relationship between IV ketamine's dissociative and psychotomimetic effects and its therapeutic action on depression and suicidal ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4065787/

Do the dissociative side effects of ketamine mediate its ... Among the examined mediators of ketamine's antidepressant response, only dissociative side effects predicted a more robust and sustained antidepressant.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf

KETALAR (ketamine hydrochloride) injection The later half-life of ketamine (beta phase) is 2.5 hours. The anesthetic state produced by KETALAR has been termed "dissociative anesthesia" in that it appears.

7. rxlist.com rxlist.com/ketalar-drug.htm

Ketalar (Ketamine Hydrochloride Injection): Side Effects, ... KETALAR is not recommended for use in patients who have not followed nil per os guidelines. Due to the potential for salivation during KETALAR administration, ...

8. cdn.pfizer.com cdn.pfizer.com/pfizercom/products/material_safety_data/526.pdf

Material Safety Data Sheet Harmful if swallowed (based on animal data) . Known Clinical Effects: Ketamine is an anesthetic agent which is known to cause double vision, motor ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/ketamine-injection-route/description/drg-20075559

Ketamine (injection route) - Side effects & uses Ketamine injection is used alone or together with other medicines to produce loss of consciousness before and during surgery or a medical procedure.

10. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470357/

Ketamine - StatPearls - NCBI Bookshelf - NIH An average dose of 2 mg/kg (1 mg/lb) is typically needed to induce around 5 to 10 minutes of anesthesia or dissociative effects.