Ketamine-assisted Psychotherapy for PTSD

Overseen By Sara Heyn, JD, PhD

Age: < 18

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Benzodiazepines, Opiates, Lamotrigine

Disqualifiers: Psychotic disorder, Bipolar, Autism, 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: 11

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore ketamine's potential, a medication sometimes used for pain and depression, in easing PTSD (posttraumatic stress disorder) symptoms in teenagers. Participants will receive three ketamine treatments, each followed by a therapy session, over six weeks. The researchers aim to determine if this combination is safe and can reduce PTSD symptoms. Teens with PTSD who are otherwise healthy might be suitable for this study. As an Early Phase 1 trial, this research focuses on understanding how ketamine works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial requires participants to stop using benzodiazepines, opiates, or lamotrigine, as these medications may interfere with ketamine's effects.

What prior data suggests that this protocol is safe for adolescents with PTSD?

Research has shown that ketamine is generally safe and well-tolerated for conditions like post-traumatic stress disorder (PTSD) and treatment-resistant depression (TRD). People usually handle ketamine well, but some side effects can occur.

Studies have identified mild side effects as the most common, such as dizziness, nausea, or a temporary rise in blood pressure. These effects are typically short-lived and resolve on their own. However, safety concerns arise when ketamine is not used in a controlled medical setting, especially with custom-mixed versions of the drug.

This study is in an early phase, focusing on how well adolescents tolerate ketamine. Early-phase studies often involve small groups and primarily assess safety, not yet proving the treatment's effectiveness. As a result, detailed safety data for adolescents may be limited. However, ketamine's use for other conditions in adults provides some confidence in its safety under medical supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for PTSD, which often include therapy and medications like SSRIs or SNRIs, ketamine-assisted psychotherapy uses ketamine, a unique active ingredient, to potentially provide rapid relief. Ketamine acts on the brain's glutamate system, thought to be pivotal in mood regulation, offering a new mechanism of action compared to traditional treatments. Researchers are excited because ketamine has shown the potential to produce quick results, potentially within hours or days, which is significantly faster than conventional medications that can take weeks to become effective. This rapid action could be a game-changer for individuals with severe PTSD, especially adolescents, who need swift and effective interventions.

What evidence suggests that ketamine-assisted psychotherapy might be an effective treatment for PTSD?

Research has shown that ketamine, which participants in this trial may receive, can help reduce PTSD symptoms. One study found that repeated ketamine infusions through an IV significantly improved PTSD symptoms. Another analysis linked more ketamine treatments to large reductions in both PTSD and depression symptoms. This improvement likely occurs because ketamine influences brain chemicals related to mood and stress. Although more research is needed, these findings suggest that ketamine could be a promising option for treating PTSD. ^{2 5 6 7 8}

Who Is on the Research Team?

Ryan J Herringa, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Christopher Nicholas, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adolescents with severe PTSD. Participants will undergo preparatory sessions, three ketamine-assisted psychotherapy sessions over six weeks, and post-session integrations. They must also be willing to record their sleep at home for seven nights.

Inclusion Criteria

Must agree not to participate in any other interventional clinical trials during the duration of the study

Meet threshold for Diagnostic and Statistical Manual (DSM-5) criteria for current PTSD as determined by the CAPS-CA at baseline

Medically and neurologically healthy on the basis of physical examination, medical history, and clinical judgement of the evaluating study medical provider

Exclusion Criteria

Persons known to have a hypersensitivity to ketamine

I have used ketamine before, either for treatment or recreationally.

Any finding(s), based on the screening process, that the PI feels would make the study unsuitable for the participant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Preparatory Sessions

Participants complete an initial set of preparatory sessions before ketamine administration

1 week

2 visits (in-person)

Treatment

Participants receive three intravenous ketamine administrations prior to psychotherapy sessions

6 weeks

3 visits (in-person)

Integration Sessions

Each dosing session is followed by three to six hours of integration sessions

6 weeks

3 visits (in-person)

Sleep Recording

Participants complete 7 nights of at-home sleep recordings using the Philips SmartSleep headband

1 week

At-home

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a 1-month follow-up assessment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine

Trial Overview The study tests the process of giving intravenous ketamine right before a psychotherapy session to see if it helps reduce PTSD symptoms in teenagers. The effectiveness and overall experience of this treatment method are being evaluated.

How Is the Trial Designed?

Group I: Adolescents with Severe PTSD Experimental Treatment 2 Interventions

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

The RTT-KaT program, which combines ketamine-assisted therapy with group psychotherapy, was well tolerated by all 128 participants, with no dropouts reported during the 12-week program.

While 49.16% of sessions noted elevated blood pressure post-treatment, most adverse effects were mild and transient, including nausea (12.05%), vomiting (2.52%), headaches (3.35%), and dizziness, indicating a good safety profile for ketamine use in this community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of intramuscular and sublingual ketamine for psychiatric treatment in the Roots To Thrive ketamine-assisted therapy program: a retrospective chart review. Tsang, VWL., Tao, B., Dames, S., et al.[2023]

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]

Ketamine has shown promise as a rapid-acting treatment for PTSD, with a single intravenous dose leading to a quick reduction in symptoms, particularly in civilian populations.

In a study involving repeated IV ketamine administration, significant improvements in PTSD symptoms were observed compared to midazolam, but this effect was not seen in veteran and military populations, indicating the need for further research on its efficacy across different groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine for Treatment of Posttraumatic Stress Disorder: State of the Field. Fremont, R., Brown, O., Feder, A., 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]

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]

In a study involving five patients with treatment-resistant depression (TRD) and comorbid PTSD, repeated oral esketamine treatment led to improvements in depressive symptoms and increased receptiveness to psychotherapy over a duration of six weeks to a year.

While most patients showed positive responses, one individual experienced symptom worsening in a stressful situation, emphasizing the importance of administering esketamine in a safe environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder. Veraart, JKE., van Westenbrugge, M., van Wulfften Palthe, JE., et al.[2023]

A systematic review of 19 studies involving 1006 patients found that combining psychotherapy with ketamine treatment for psychiatric disorders generally leads to positive outcomes, particularly for conditions like substance use disorders and treatment-resistant depression.

Despite the promising results, the significant variability in psychotherapy types and ketamine protocols across studies means that more standardized and larger randomized controlled trials are needed to determine the best ways to integrate these treatments effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review. Kew, BM., Porter, RJ., Douglas, KM., et al.[2023]

A ketamine-assisted therapy program evaluated in a community of practice model showed significant improvements in mental health outcomes for 94 patients, with 91% reporting reduced anxiety, 79% reporting reduced depression, and 86% of PTSD patients screening negative after treatment.

The program demonstrated clinically significant enhancements in work/life functionality, with 92% of participants experiencing improvements, highlighting ketamine's potential as an effective treatment for those with treatment-resistant mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression. Dames, S., Kryskow, P., Watler, C.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10979792/

Effectiveness of Ketamine for the Treatment of Post- ... Outcomes. The primary outcome of interest was the improvement in PTSD symptoms, assessed using the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) ...

2. cda-amc.ca cda-amc.ca/sites/default/files/pdf/htis/2022/RC1420-Ketamine-for-treatment-resistant-depression-and-PTSD.pdf

Ketamine for Adults With Treatment-Resistant Depression ... One randomized controlled trial with small sample size found that repeated IV ketamine infusions significantly improved post-traumatic stress disorder symptoms ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40848332/

A retrospective analysis of ketamine intravenous therapy ... Results: The number of KIT treatments was associated with significant reductions in PTSD and depression symptoms. The model using a logarithmic ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02397889

Study Details | NCT02397889 | Ketamine as a Treatment ... The purpose of this study is to see whether ketamine, when given repeatedly intravenously can produce a quick and persistent improvement in PTSD symptoms. At ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ibra.12094

Ketamine as a therapeutic agent in major depressive ... In this article, the effectiveness of ketamine as a potential therapeutic for PTSD and MDD along with its mechanisms of action, clinical trials, and possible ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602384/

Ketamine for Adults With Treatment-Resistant Depression or ... A 2022 CADTH report 24 on the use of ketamine for PTSD or TRD found insufficient evidence to provide definitive conclusions about its clinical effectiveness.

7. fda.gov fda.gov/drugs/human-drug-compounding/fda-warns-patients-and-health-care-providers-about-potential-risks-associated-compounded-ketamine

FDA warns about compounded ketamine for psychiatric ... FDA has identified potential safety concerns associated with the use of compounded ketamine products from compounders and telemedicine platforms.

8. psychopharmacologyinstitute.com psychopharmacologyinstitute.com/publication/ketamine-guide-pharmacology-indications-dosing-guidelines-and-adverse-effects-2924/

Ketamine Guide: Pharmacology, Indications, Dosing ... Limited safety data available; case series of 4 ... Nonconventional interventions for chronic post-traumatic stress disorder: Ketamine ...