Ketamine for Mental Illness

Overseen By Arjay Cordero

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Disqualifiers: Psychotic disorder, Pregnant, Ketamine use, 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

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how ketamine, a medication sometimes used in anesthesia, might cause dissociative symptoms, such as feelings of disconnect from thoughts or surroundings. Researchers administer a single infusion of ketamine to participants to observe its effects. The study is open to patients currently in Stanford Medical Center’s neuro inpatient units who have not received ketamine in the last week and have not experienced a negative reaction to it before. This trial may suit those dealing with mental health challenges who are curious about ketamine's effects. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

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

Research shows that ketamine can cause temporary side effects. Some studies have found that people might feel confused or experience hallucinations. These effects usually don't last long. After taking ketamine, avoid driving or using heavy machinery for about 24 hours.

The FDA has approved ketamine for use as an anesthetic, indicating it has been studied and found safe for certain uses. However, misuse can lead to psychological dependence, creating a strong urge to continue using the drug.

Overall, while ketamine has known risks, it has been used safely in medical settings for years. For any concerns, consult the study team. They can help clarify what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ketamine hydrochloride for mental illness because it offers a fast-acting alternative compared to traditional treatments like antidepressants, which can take weeks to show effects. Ketamine works differently by targeting the brain's glutamate system, rather than the serotonin or norepinephrine pathways that most standard medications focus on. This unique mechanism not only speeds up the relief of symptoms but also opens new possibilities for treatment-resistant cases, where conventional options might have failed. Additionally, its administration as a single infusion makes it a convenient and potentially more accessible option for patients.

What evidence suggests that ketamine might be an effective treatment for mental illness?

Research shows that ketamine, which participants in this trial will receive, can help treat certain mental health issues, especially depression. Studies have found that it can quickly ease depression symptoms, sometimes within hours of just one treatment, with the strongest effects seen around 24 hours later. Many patients have reported significant improvements in their depression and anxiety after using ketamine. Additionally, ketamine is considered safe, with no major side effects reported. These findings suggest that ketamine could effectively manage mental health symptoms. ^{4 6 7 8 9}

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 who are inpatients at Stanford Medical Center's clinical neuro units. Women must use effective birth control during the study, including hormonal methods, barrier methods with spermicide, IUDs, or abstinence.

Inclusion Criteria

I am older than 18 years.

I am using or will use effective birth control during the study.

You are an inpatient at Stanford Medical Center's clinical neuro units.

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 symptoms and other effects of ketamine

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine Hydrochloride

Trial Overview The study aims to understand how ketamine hydrochloride affects brain function related to dissociative symptoms often seen in mental illness and disruptive behaviors.

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 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]

Ketamine hydrochloride (50mg/ml) remains chemically stable for up to 180 days when stored in polypropylene syringes at room temperature, making it suitable for advance preparation.

The study confirmed that the concentration of ketamine does not fall below 90% of its initial value during this period, ensuring its efficacy for use as an anesthetic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term stability of ketamine hydrochloride 50mg/ml injection in 3ml syringes. Huvelle, S., Godet, M., Hecq, JD., et al.[2022]

Ketamine hydrochloride has shown rapid and significant antidepressant effects in patients with treatment-resistant mood and anxiety disorders, although the studies supporting this have small sample sizes and limited long-term data.

While ketamine may offer benefits for some patients, there are important safety concerns and limitations in the existing research that must be considered when using it as an off-label treatment for psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. Sanacora, G., Frye, MA., McDonald, W., et al.[2022]

In a study of 85 patients with treatment-resistant depression receiving intravenous ketamine, only 18.3% responded positively during the initial treatment phase, but nearly half of the patients chose to continue with maintenance therapy, indicating perceived benefits despite low response rates.

The study found that 32.9% of patients continued on maintenance ketamine, suggesting that even with limited efficacy, many patients felt significant improvement in their symptoms, highlighting the potential for ketamine as a treatment option for those with difficult-to-treat depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome in outpatients with depression treated with acute and maintenance intravenous ketamine: A retrospective chart review. Sakurai, H., Jain, F., Foster, S., et al.[2021]

Ketamine has shown potential benefits in treating psychiatric conditions like major depression and in supporting abstinence from alcohol and opiates, based on a literature review of studies from 2003 to 2013.

Despite its promising therapeutic effects, ketamine poses a risk of abuse and dependence, leading to various somatic, psychiatric, and cognitive complications, highlighting the need for careful consideration in its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ketamine: psychiatric indications and misuses]. Delimbeuf, N., Petit, A., Karila, L., et al.[2015]

Ketamine shows promise as a treatment for treatment-resistant depression (TRD), but its use can lead to common adverse events, which are usually temporary.

A case of apnea during a slow sub-anesthetic infusion of ketamine highlights a rare but serious potential side effect, emphasizing the need for careful monitoring and management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression. Gómez-Revuelta, M., Fernández-Rodríguez, M., Boada-Antón, L., et al.[2021]

A meta-analysis of 36 studies involving 725 healthy volunteers found that acute administration of ketamine significantly increases transient schizophrenia-like symptoms, with a large effect size for both total (SMD = 1.50) and positive symptoms (SMD = 1.55) compared to placebo.

The study suggests that using a bolus followed by a constant infusion of ketamine is associated with a greater increase in positive symptoms, indicating that bolus doses should be avoided in therapeutic settings to reduce the risk of inducing psychotic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Ketamine With Psychiatric Symptoms and Implications for Its Therapeutic Use and for Understanding Schizophrenia: A Systematic Review and Meta-analysis. Beck, K., Hindley, G., Borgan, F., et al.[2021]

Ketamine has shown significant promise as a rapidly acting antidepressant for treatment-resistant major depressive disorder (MDD), with potential efficacy also noted in bipolar depression and post-traumatic stress disorder.

While most side effects of ketamine, such as neuropsychiatric and cardiovascular disturbances, are short-lived, the long-term safety profile remains uncertain, highlighting the need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for treatment-resistant depression: recent developments and clinical applications. Schwartz, J., Murrough, JW., Iosifescu, DV.[2019]

Low-dose ketamine infusion has shown rapid effects in reducing suicidal thoughts, making it a potentially valuable treatment in general hospital settings for patients at risk of suicide.

The treatment was reported to be efficient and well-tolerated in a patient who had recently attempted suicide, suggesting a favorable benefit-risk ratio for its use in acute care situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine Use for Suicidal Ideation in the General Hospital: Case Report and Short Review. Vulser, H., Vulser, C., Rieutord, M., et al.[2022]

A case series of 9 daily ketamine users revealed severe urinary symptoms, including dysuria and hematuria, linked to chronic ketamine use, with all patients diagnosed with severe ulcerative cystitis.

Investigations showed bladder wall thickening and inflammation, and cessation of ketamine use along with treatment provided some relief, highlighting the potential for serious bladder issues associated with recreational ketamine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine-associated ulcerative cystitis: a new clinical entity. Shahani, R., Streutker, C., Dickson, B., et al.[2022]

A review of 34 articles revealed 312 cases of overdose and 138 deaths related to ketamine use, primarily in recreational settings and often involving polydrug use, highlighting significant risks associated with misuse.

Despite concerns about ketamine's safety in non-medical contexts, no overdoses or deaths were reported from its use as an antidepressant in therapeutic settings, suggesting it can be safely prescribed when used appropriately.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overdoses and deaths related to the use of ketamine and its analogues: a systematic review. Chaves, TV., Wilffert, B., Sanchez, ZM.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8801551/

Role of Ketamine in the Treatment of Psychiatric Disorders Results indicated that hospital admissions were reduced by 65%, and inpatient hospital days were reduced by 70% following oral ketamine treatment. No evidence ...

2. 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.

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2766225

Association of Ketamine With Psychiatric Symptoms and ... This meta-analysis assesses the psychopathological outcomes in healthy volunteers and patients with schizophrenia treated with ketamine and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1697260023000649

The efficacy and safety of ketamine for depression in ... Our findings showed that ketamine is a safe (no significant adverse events reported) and effective drug to control depression symptoms and correlated symptoms, ...

5. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.710338/full

An Integrative Approach to Ketamine Therapy May ... Results indicated that ketamine had an effect on depressive symptoms within 4 h following a single infusion, with peak efficacy at 24 h. Ketamine efficacy was ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/016812s040lbl.pdf

ketamine - accessdata.fda.gov NO RESIDUAL PSYCHOLOGICAL. EFFECTS ARE KNOWN TO HAVE RESULTED FROM USE OF KETALAR. THE INCIDENCE OF THESE EMERGENCE PHENOMENA IS LEAST IN THE ELDERLY (OVER 65.

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

Ketamine - StatPearls - NCBI Bookshelf - NIH Patients should not drive, use heavy machinery, or perform potentially hazardous activities for up to 24 hours following ketamine administration ...

8. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=14017

Ketalar® Injection (Ketamine Hydrochloride) Preclinical safety data. Animal research has shown that ketamine can induce NMDA antagonist-induced neuronal cell death in juvenile animals (apoptosis) when ...

9. drugs.com drugs.com/ketamine.html

Ketamine: Uses, Dosage, Side Effects, Warnings Abuse of the ketamine may lead to a moderate to low potential for physical dependence but high psychological dependence. Drugs that are ...