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

16 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial combines writing therapy and ketamine injections to help people with chronic PTSD who don't fully benefit from current treatments. Ketamine makes the brain more adaptable, and writing about trauma helps reduce its emotional impact. Ketamine has shown benefits for treating PTSD symptoms and is being explored in combination with psychotherapy for lasting effects.

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.

What data supports the effectiveness of the drug Ketamine for treating Post-Traumatic Stress Disorder?

Research shows that ketamine can rapidly reduce PTSD symptoms, especially in civilian populations, and has been effective in decreasing depression and anxiety when combined with psychotherapy. However, its effectiveness in military populations is less clear, and further studies are needed to explore its benefits. ^{1 2 3 4 5}

What makes the treatment of Written Exposure Therapy + Ketamine unique for PTSD?

This treatment combines Written Exposure Therapy, which is a brief and efficient form of exposure therapy, with ketamine, a drug known for its rapid action and novel mechanism in treating mental health conditions, offering a potentially faster and more effective approach for PTSD compared to traditional treatments. ^{2 5 6 7 8}

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

Eligibility Criteria

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

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

Treatment Details

Interventions

• Ketamine
• Written Exposure Therapy

Participant Groups

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+

Findings from Research

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 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, 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]

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]

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]

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

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

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. [2023]

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

Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series. [2023]

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

Repeated ketamine infusions for antidepressant-resistant PTSD: Methods of a multicenter, randomized, placebo-controlled clinical trial. [2020]

6. 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]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

An Open Pilot Trial of Written Exposure Therapy for Patients With Post-Traumatic Stress Disorder in Korea. [2021]

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

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