Oxytocin for PTSD

Recruiting at 1 trial location

Overseen By Julianne Christina Flanagan, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must be taking: Psychotropic medications

Must not be taking: Anxiolytics, Antidepressants, Mood stabilizers

Disqualifiers: Psychotic, Bipolar, Suicidal, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 10 weeks

185 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You don't have to stop taking your current medications, but you must be on a stable dose of any psychotropic medications for at least four weeks before starting the trial.

Will I have to stop taking my current medications?

Participants must be on a stable dose of their current psychotropic medications for at least four weeks before starting the study. If you have recently started any new medications, you may need to wait until they are stable for four weeks before participating.

What data supports the idea that Oxytocin for PTSD is an effective drug?

The available research shows that oxytocin, when combined with Prolonged Exposure (PE) therapy, may help reduce PTSD symptoms and improve therapy adherence. In one study, veterans who used oxytocin reported lower PTSD and depression symptoms and better working relationships with their therapists, although these results were not statistically significant. Another study found that oxytocin helped improve PTSD symptoms and relationship satisfaction in veterans and their partners. These findings suggest that oxytocin could be a promising addition to existing PTSD treatments, but more research is needed to confirm its effectiveness. ^{1 2 3 4 5}

What data supports the effectiveness of the drug oxytocin for PTSD?

Research suggests that oxytocin may help improve PTSD symptoms when combined with therapy by enhancing social interactions and learning to overcome fear. Some studies show that oxytocin can reduce PTSD symptoms and improve therapy outcomes, but more research is needed to confirm these findings. ^{1 2 3 4 5}

What safety data exists for oxytocin treatment in PTSD?

The provided research does not contain any safety data for oxytocin or its related names (Pitocin, Syntocinon, Viatocinon, oxytocin, Placebo, Control, Dummy Treatment) in the context of PTSD treatment. The studies focus on palonosetron and its use in chemotherapy-induced nausea and vomiting, not on oxytocin. ^{6 7 8 9 10}

Is the drug oxytocin a promising treatment for PTSD?

Yes, oxytocin is a promising drug for treating PTSD. It may help reduce PTSD symptoms, improve therapy outcomes, and enhance social interactions, making patients feel safer and more engaged in treatment. ^{1 2 3 11 12}

How does the drug oxytocin differ from other treatments for PTSD?

Oxytocin is unique because it is used to enhance existing therapies like Prolonged Exposure (PE) therapy by reducing fear responses and improving social interactions, which are crucial for PTSD treatment. It is administered intranasally before therapy sessions, potentially improving therapy adherence and outcomes by creating a sense of safety and enhancing the therapeutic alliance. ^{1 2 3 11 12}

What is the purpose of this trial?

Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition that disproportionately affects Veterans. Prolonged Exposure (PE) therapy is a "gold standard" treatment for PTSD. However, approximately one-third of Veterans fail to receive an adequate dose of treatment because they prematurely drop out of PE therapy. There is also room to improve PE treatment outcomes. Consistent with the VA Office of Research and Development initiative to develop effective treatments for PTSD, the proposed randomized clinical trial will examine the ability of oxytocin (as compared with placebo) combined with PE to reduce PTSD symptom severity, improve the rate of PTSD symptom reduction, and to enhance PE treatment retention and adherence. This two-site study will leverage the investments made in the nationwide rollout off PE therapy and has the potential to significantly improve mental health care among Veterans, advance the science in this area, and identify mechanisms underlying positive PTSD treatment response. Participants may choose to complete this research study via home-based telemedicine (HBT) care (i.e. service delivery to patients in their homes using consumer friendly, video-conferencing technology). HBT sessions will be delivered via standard desk, laptop computer, tablet, or smartphone using VA approved applications. All procedures that take place via telemedicine will be performed and completed as though they were in-person/in-office

Research Team

Julianne Christina Flanagan, PhD

Principal Investigator

Ralph H. Johnson VA Medical Center, Charleston, SC

Eligibility Criteria

This trial is for Veterans with PTSD, who can consent and perform well on a mental status exam. They may have mood or anxiety disorders but not bipolar disorder or current severe suicidal thoughts. Stable psychotropic medication use is okay.

Inclusion Criteria

I have been on a stable dose of my mental health medication for at least 4 weeks.

You may have a mood disorder, except for bipolar affective disorder.

The study is only open to military veterans.

Exclusion Criteria

I started taking medication for anxiety, depression, or mood stabilization in the last 4 weeks.

Pregnancy or breastfeeding for women

Participants who present a serious suicide risk or are likely to require hospitalization during the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Prolonged Exposure (PE) therapy combined with either oxytocin or placebo for PTSD

10 weeks

Sessions may be completed via home-based telemedicine

Follow-up

Participants are monitored for PTSD symptom severity and treatment adherence

6 months

Follow-up assessments at 3 and 6 months

Treatment Details

Interventions

• Oxytocin
• Placebo

Trial Overview The study tests if oxytocin can improve PTSD symptoms and treatment retention in Veterans undergoing Prolonged Exposure therapy, compared to a placebo. Participants can join sessions via telemedicine using VA approved apps.

Participant Groups

Group I: Oxytocin Experimental Treatment 1 Intervention

40 IU intranasal oxytocin

Group II: Placebo Placebo Group 1 Intervention

intranasal saline spray

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

San Francisco VA Health Care System

Collaborator

Trials

11

Recruited

865,000+

Findings from Research

This Phase II study aims to evaluate the effectiveness of intranasal oxytocin combined with Prolonged Exposure (PE) therapy in reducing PTSD symptoms among U.S. military veterans, using a randomized, double-blind, placebo-controlled design.

The study will assess not only the reduction in PTSD symptom severity but also the rate of improvement and retention in therapy, providing insights into how oxytocin may enhance the effectiveness of existing PTSD treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. Flanagan, JC., Mitchell, JM., Baker, NL., et al.[2021]

In a study using a rat model of PTSD, systemic administration of oxytocin (OXT) was found to impair the extinction of fear memories, suggesting that it may not be effective for treating PTSD as previously thought.

While OXT delayed fear extinction in non-stressed (sham) rats, it had no significant effect on the impaired fear extinction observed in stressed (SPS) rats, indicating that OXT's role in PTSD treatment may require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of systemic administration of oxytocin on contextual fear extinction in a rat model of post-traumatic stress disorder. Eskandarian, S., Vafaei, AA., Vaezi, GH., et al.[2021]

A pilot study involving 10 U.S. veterans with PTSD and their partners showed that combining brief Cognitive-Behavioral Conjoint Therapy (bCBCT) with intranasal oxytocin led to significant improvements in relationship satisfaction and PTSD symptoms, with no serious adverse events reported.

Veterans experienced a large reduction in PTSD severity (effect size of 1.87), while both partners reported moderate to large improvements in relationship satisfaction, indicating that this approach is feasible and may enhance the effectiveness of traditional therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder. Sippel, LM., Khalifian, CE., Knopp, KC., et al.[2023]

Oxytocin (OXT) shows potential to enhance psychotherapeutic treatments for PTSD by reducing stress responses and aiding recovery, which could lead to improved treatment outcomes for patients.

OXT may help counteract memory impairments caused by stress and promote social support seeking, both of which are important for resilience and effective therapy in PTSD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication-Enhanced Psychotherapy for Posttraumatic Stress Disorder: Recent Findings on Oxytocin's Involvement in the Neurobiology and Treatment of Posttraumatic Stress Disorder. Preckel, K., Trautmann, S., Kanske, P.[2022]

A pilot study involving 17 participants with PTSD explored the combination of intranasal oxytocin and Prolonged Exposure (PE) therapy, showing that oxytocin may help reduce PTSD and depression symptoms and improve the therapeutic alliance, although these results were not statistically significant.

The study demonstrated the feasibility and safety of using oxytocin with PE therapy, suggesting that larger studies are needed to confirm its effectiveness and understand how it might enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. Flanagan, JC., Sippel, LM., Wahlquist, A., et al.[2019]

In a phase II study involving 58 patients receiving moderately emetogenic chemotherapy, the combination of palonosetron, dexamethasone, and aprepitant resulted in an 88% complete response rate in preventing nausea and vomiting during the first 24 hours after treatment.

The treatment was well tolerated with no unexpected adverse events, demonstrating that this combination therapy is both safe and highly effective for managing chemotherapy-induced nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. Grote, T., Hajdenberg, J., Cartmell, A., et al.[2018]

Palonosetron is a highly effective 5-HT(3) receptor antagonist for preventing chemotherapy-induced nausea and vomiting, with 71.9% of the drug remaining unchanged in plasma for up to 96 hours after administration.

The drug is primarily eliminated through the kidneys, with 83% of the dose recovered in urine, and it was generally well tolerated by participants, with no significant cardiac effects observed during monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. Stoltz, R., Parisi, S., Shah, A., et al.[2022]

In a study involving 384 patients at risk for postoperative nausea and vomiting (PONV), a single intravenous dose of 0.075 mg palonosetron significantly improved the complete response rates at 24 and 72 hours compared to a placebo, with rates of 68.1% and 65.3% respectively.

The incidence of nausea and vomiting was also lower in the palonosetron group at 2, 24, and 72 hours post-treatment, while the safety profile was comparable to the placebo, indicating that palonosetron is an effective and safe option for managing PONV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective, randomized, double-blind, multicenter trial to evaluate the therapeutic efficacy and safety of palonosetron in the treatment of postoperative nausea and vomiting over a 72-h period. Hahm, TS., Hwang, JW., Kim, WH., et al.[2021]

The combination of netupitant and palonosetron is effective in preventing both acute and delayed nausea and vomiting caused by moderately and highly emetogenic chemotherapy, as supported by phase II and III clinical trials.

This treatment offers a convenient single-capsule dosage and has a favorable side effect profile, although its high cost and administration logistics may pose challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of netupitant and palonosetron in chemotherapy-induced nausea and vomiting. Abramovitz, RB., Gaertner, KM.[2018]

Palonosetron, a new 5-HT3 receptor antagonist, has been shown to effectively prevent both acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately to highly emetogenic chemotherapy, demonstrating a longer half-life and higher binding affinity than older agents.

In clinical trials, palonosetron was as effective in controlling CINV during subsequent chemotherapy cycles as it was during the initial treatment, with no significant differences in safety profiles compared to other 5-HT3 receptor antagonists like ondansetron and dolasetron.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. Navari, RM.[2018]

Oxytocin may enhance the effectiveness of cognitive-behavioral therapy (CBT) for posttraumatic stress disorder (PTSD) by promoting a sense of safety, which is crucial for successful treatment.

The proposed mechanisms for oxytocin's effectiveness include reducing fear responses by decreasing amygdala activation and enhancing social interactions, both of which are important for patients with PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder. Olff, M., Langeland, W., Witteveen, A., et al.[2019]

Oxytocin has been studied for its potential to alleviate symptoms of PTSD, showing some positive effects according to research by Koch et al.

However, the effects observed were small, raising questions about the clinical significance and overall effectiveness of oxytocin as a treatment for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oxytocin for the treatment of PTSD?] Dumont, GJH.[2021]

References

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

Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. [2021]

2. Iran pubmed.ncbi.nlm.nih.gov

Effects of systemic administration of oxytocin on contextual fear extinction in a rat model of post-traumatic stress disorder. [2021]

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

Pilot test of intranasal oxytocin as an enhancer of brief couples therapy for posttraumatic stress disorder. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Medication-Enhanced Psychotherapy for Posttraumatic Stress Disorder: Recent Findings on Oxytocin's Involvement in the Neurobiology and Treatment of Posttraumatic Stress Disorder. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. [2019]

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

Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, metabolism and excretion of intravenous [l4C]-palonosetron in healthy human volunteers. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

A prospective, randomized, double-blind, multicenter trial to evaluate the therapeutic efficacy and safety of palonosetron in the treatment of postoperative nausea and vomiting over a 72-h period. [2021]

9. England pubmed.ncbi.nlm.nih.gov

The role of netupitant and palonosetron in chemotherapy-induced nausea and vomiting. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist. [2018]

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

A psychobiological rationale for oxytocin in the treatment of posttraumatic stress disorder. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

[Oxytocin for the treatment of PTSD?] [2021]