What side effects are associated with this type of intervention?

Common treatments for PTSD include SSRIs, SNRIs, and prazosin. SSRIs and SNRIs can cause side effects such as nausea, insomnia, sexual dysfunction, and increased anxiety. Prazosin, used primarily for sleep disturbances and nightmares, may cause dizziness, headache, and hypotension. Neurosteroids like pregnenolone, which are being studied for their anxiolytic and neuroprotective effects, may have side effects including mood swings, hormonal imbalances, and potential interactions with other medications. Patients should discuss these potential side effects with their healthcare provider to determine the best treatment plan.

What prior FDA approvals exist?

The FDA has approved several medications for the treatment of Post-Traumatic Stress Disorder (PTSD), primarily focusing on selective serotonin reuptake inhibitors (SSRIs) such as sertraline and paroxetine. These medications help manage symptoms by modulating neurotransmitter systems. While pregnenolone, a neurosteroid with potential anxiolytic and neuroprotective effects, is currently being studied for its efficacy in treating PTSD, it has not yet received FDA approval. Other treatments under investigation include prazosin for sleep disturbances and nightmares, and second-generation antipsychotics for patients with prominent psychotic symptoms.

What other types of research exist?

Promising novel alternatives to Pregnenolone for PTSD treatment in 2024 include: 1) Allopregnanolone, a neurosteroid with potent anxiolytic and antidepressant effects, currently being studied for its efficacy in PTSD. 2) Brexanolone, an FDA-approved neurosteroid for postpartum depression, which is being explored for its potential benefits in PTSD. 3) Cannabidiol (CBD), a non-psychoactive component of cannabis, which has shown anxiolytic and neuroprotective properties in preliminary studies. 4) MDMA-assisted psychotherapy, which has demonstrated significant efficacy in reducing PTSD symptoms in phase 3 clinical trials.

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Neurosteroid

Pregnenolone for PTSD

Phase 2

Recruiting

Led By Jennifer C Naylor, PhD

Research Sponsored by VA Office of Research and Development

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Females will be required to use a medically and study approved contraceptive or otherwise not be of child-bearing potential

DSM-5 diagnosis of PTSD with CAPS-5 Total Score 3

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, an average of 5 years

Summary

This trial tests pregnenolone, a natural hormone booster, to see if it can help Iraq/Afghanistan-era Veterans with PTSD who need better treatment options. Pregnenolone works by balancing brain chemicals to improve mood and reduce PTSD symptoms. Pregnenolone has been studied for its brain-protective effects, particularly in relation to its conversion to estradiol.

Who is the study for?

This trial is for Iraq/Afghanistan-era Veterans with PTSD who can commit to a 10-week study without changing their psychiatric medications. They must not have severe medical conditions, be pregnant or breastfeeding, use hormonal therapies, or have substance abuse issues. Stable non-hormonal birth control is required for women.

What is being tested?

The study tests if pregnenolone improves PTSD symptoms compared to a placebo over 10 weeks. Participants will receive either the hormone or placebo and undergo regular health assessments during six in-person visits and check-in calls.

What are the potential side effects?

While specific side effects are not listed, pregnenolone may cause hormonal changes that could affect mood and physical health. Allergic reactions are possible, as well as potential exacerbation of PTSD symptoms.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am using approved birth control or cannot become pregnant.

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I have been diagnosed with PTSD and my CAPS-5 score is at least 3.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, an average of 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, an average of 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, an average of 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in Clinician Administered PTSD Scale for DSM-5 (Visit 6-Baseline)

Secondary study objectives

Change in Brief Pain Inventory, Short Form (Visit 6-Baseline)

Change in Hamilton-Depression Inventory (Visit 6-Baseline)

Side effects data

From 2011 Phase 4 trial • 80 Patients • NCT01409096

Sinusitis

Corneal ulceration

Skin abscess followed by allergic reaction to antibiotic used to treat it

Skin rash

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

Pregnenolone

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: PregnenoloneExperimental Treatment1 Intervention

Placebo lead in 14 DAYS, followed by Pregnenolone 50 mg BID x 14 DAYS, followed by Pregnenolone 150 mg BID x 14 DAYS, followed by Pregnenolone 250 mg BID x thereafter for the remainder of the 8-week trial

Group II: PlaceboPlacebo Group1 Intervention

Same as pregnenolone (active study medication), except placebo dispensed.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pregnenolone

2011

Completed Phase 4

~770

0 / 2Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for PTSD include neurosteroids like pregnenolone, SSRIs, SNRIs, and alpha-adrenergic receptor blockers. Neurosteroids such as pregnenolone modulate neurotransmitter systems and may have anxiolytic and neuroprotective effects, potentially improving mood and cognitive function. SSRIs and SNRIs work by increasing serotonin and norepinephrine levels in the brain, which can help alleviate symptoms of depression and anxiety commonly associated with PTSD. Alpha-adrenergic receptor blockers like prazosin reduce noradrenergic hyperactivity, which can help mitigate nightmares and sleep disturbances. These mechanisms are crucial for PTSD patients as they target the underlying neurobiological disruptions, offering symptom relief and improving overall quality of life.

PTSD: from neurobiology to pharmacological treatments.