Written Exposure Therapy + Ketamine for Post-Traumatic Stress Disorder

Overseen By Oneysha Brown, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Opioids, Benzodiazepines

Disqualifiers: Pregnancy, Unstable medical illnesses, Bipolar, Psychotic disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how combining written therapy with ketamine can help individuals with chronic PTSD (Post-Traumatic Stress Disorder) improve and maintain their well-being. Participants will undergo written exposure therapy, which involves writing about traumatic experiences, alongside ketamine infusions. This treatment may enhance the brain's ability to change and heal. It is suitable for those struggling with PTSD symptoms who are not currently in therapy. The approach aims to determine if combining these treatments leads to improved and lasting relief from PTSD symptoms. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

You may need to stop taking certain medications like opioid medications or daytime benzodiazepines two weeks before the study starts. However, you can continue other psychotropic medications if the dose has been stable for at least three months.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketamine infusions are safe and generally well-tolerated for people with PTSD. Some studies reported that patients experienced only short-term side effects, such as feeling disconnected or spacey, which typically did not last long.

Studies on Written Exposure Therapy (WET) have also demonstrated its safety and effectiveness in treating PTSD. This brief therapy involves writing about trauma, and most participants complete the treatment without quitting.

Both ketamine and WET have undergone testing in various studies and have been found safe for PTSD, making them promising options for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike traditional treatments for PTSD, which often involve medications like SSRIs or prolonged exposure therapy, this new approach combines ketamine with Written Exposure Therapy. Researchers are excited because ketamine acts on the brain's NMDA receptors, offering rapid relief from symptoms, often within hours or days, compared to weeks with standard treatments. Additionally, the combination with Written Exposure Therapy could enhance long-term benefits by addressing traumatic memories directly, making this approach potentially more effective and faster-acting than current options.

What evidence suggests that this trial's treatments could be effective for PTSD?

Research has shown that ketamine, administered alongside Written Exposure Therapy (WET) in this trial, can quickly and consistently improve PTSD symptoms. A large study involving over 8,000 patients found that ketamine therapy significantly reduced PTSD symptoms. Another study found that ketamine led to lasting improvements in anxiety and depression, common in PTSD patients. WET is also effective, significantly reducing PTSD symptoms and showing results similar to more intensive treatments. Multiple studies have found that WET works well for various PTSD cases, even when other mental health issues are present. This trial will explore the combination of ketamine with WET, which might enhance their effectiveness, as ketamine could help the brain adapt, improving the therapy's efficacy. ^{1 2 6 7 8}

Who Is on the Research Team?

Oneysha Brown, BA

Principal Investigator

Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai

Adriana Feder, MD

Principal Investigator

Depression and Anxiety Center, Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

Inclusion Criteria

Participants must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign a written informed consent document

You need to have someone close to you who can sign a contract agreeing to contact the study doctor if you experience thoughts of suicide or manic symptoms.

Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year)

Exclusion Criteria

You have a history of a condition that affects the development of your brain, like autism or a pervasive developmental disorder.

You have been diagnosed with bulimia nervosa or anorexia nervosa.

Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a total of six ketamine infusions and participate in five sessions of Written Exposure Therapy (WET)

6 weeks

6 visits for ketamine infusions, 5 visits for WET sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, with weekly assessments until 12 weeks following the start of WET

12 weeks

Weekly assessments

Extended Follow-up

Participants who remain improved are assessed monthly for up to 24 weeks

24 weeks

Monthly assessments

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Written Exposure Therapy

How Is the Trial Designed?

Group I: Ketamine and Written Exposure Therapy Experimental Treatment 2 Interventions

Intravenous Ketamine 0.5 mg/kg and Written Exposure Therapy

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?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

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]

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]

Written exposure therapy (WET) significantly reduced PTSD symptoms in Korean patients, with 60.9% of participants no longer meeting PTSD criteria at 6 weeks, increasing to 77.8% at 24 weeks, demonstrating its efficacy.

The therapy also improved depressive symptoms and global functioning, with a low dropout rate of 8%, indicating that WET is a feasible and effective treatment option for PTSD in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open Pilot Trial of Written Exposure Therapy for Patients With Post-Traumatic Stress Disorder in Korea. Park, JE., Choi, KS., Han, YR., et al.[2021]

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]

Ketamine, an NMDA receptor antagonist, shows promising rapid antidepressant effects in PTSD, with evidence from various studies including case reports and randomized trials, indicating its potential as a treatment option for this challenging condition.

Despite the variability in clinical presentation and treatment approaches, ketamine demonstrates encouraging safety and efficacy signals, suggesting it could be a valuable off-label intervention for patients with chronic, refractory PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. Ragnhildstveit, A., Roscoe, J., Bass, LC., et al.[2023]

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. 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165178125003373

A retrospective analysis of ketamine intravenous therapy ... In a large real-world sample of 8,136 PTSD patients (87 % with comorbid depression), Ketamine Intravenous Therapy (KIT) significantly reduced PTSD and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40051583/

Ketamine-Assisted Psychotherapy Provides Lasting and ... KAP produced sustained reductions in anxiety, depression, and PTSD, with symptom improvement lasting well beyond the duration of dosing and integration ...

5. nature.com nature.com/articles/s41386-023-01606-3

Long term structural and functional neural changes ... Although PTSD symptoms improved equally in both groups, post-treatment, ketamine recipients showed a lower amygdala (−0.33, sd = 0.13, 95%HDI [− ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0166432822000729

The safety and efficacy of ketamine NMDA receptor blocker ... All qualified five randomized clinical studies showed rapid and clear benefits of Ketamine infusion for PTSD symptoms resistant to conventional medications.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6457782/

Ketamine as treatment for post-traumatic stress disorder Safety of ketamine for use in PTSD. As with any novel use of a medication, it is important to investigate the potential harms from side ...

8. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.focus.20230006

Ketamine for Treatment of Posttraumatic Stress Disorder In this study, repeated ketamine infusions were also found to be safe and well tolerated in PTSD, with only transient emergence of dissociative ...