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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

The objectives of this study are to investigate the feasibility, tolerability, and preliminary efficacy of repeated ketamine-assisted psychotherapy sessions in adolescents with severe posttraumatic stress disorder. The study will enroll adolescents with a current diagnosis of posttraumatic stress disorder (PTSD) to complete three intravenous ketamine administrations immediately prior to a psychotherapy session over the span of six weeks. All participants will complete an initial set of preparatory sessions, and each dosing session will be followed by three to six hours of integration sessions. Finally, participants will complete 7 nights of at-home sleep recordings. The investigators hypothesize that this protocol will be well-tolerated by adolescents and that patients will experience decreases in PTSD symptom severity at follow-up.

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 data supports the effectiveness of the drug ketamine-assisted psychotherapy for PTSD?

Research shows that ketamine can quickly reduce PTSD symptoms, especially when given repeatedly, and combining it with psychotherapy may improve outcomes. In a study, 86% of participants with PTSD saw significant improvements after ketamine-assisted therapy, highlighting its potential as an effective treatment. ^{1 2 3 4 5}

Is ketamine-assisted psychotherapy safe for humans?

Ketamine has been used safely for decades, and studies suggest it is generally safe for treating mental health conditions like depression and anxiety, though it can cause side effects like dissociation (feeling disconnected from reality) and increased blood pressure/heart rate. ^{1 3 6 7 8}

How is ketamine-assisted psychotherapy different from other PTSD treatments?

Ketamine-assisted psychotherapy is unique because it combines the psychedelic effects of ketamine with psychotherapy, unlike traditional PTSD treatments that often use medications or therapy alone. This approach leverages ketamine's rapid-acting antidepressant properties and its ability to enhance therapeutic experiences, offering a novel option for those who do not fully respond to existing treatments. ^{3 4 5 7 9}

Research Team

Ryan J Herringa, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Christopher Nicholas, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. 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]

2. Switzerland 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. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Ketamine and psychotherapy for the treatment of psychiatric disorders: systematic review. [2023]

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

Ketamine for Treatment of Posttraumatic Stress Disorder: State of the Field. [2023]

6. 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]

7. England 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. [2023]

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

Repeated oral esketamine in patients with treatment resistant depression and comorbid posttraumatic stress disorder. [2023]

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

A Pilot Study Comparing a Community of Practice Program with and without Concurrent Ketamine-Assisted Therapy. [2023]