Lorazepam for PTSD

Overseen By Vitaliana R Vasquez, BA

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must not be taking: Benzodiazepines, Opioids

Disqualifiers: Neurologic, Cardiovascular, Pulmonary, 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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A substantial majority of Veterans with posttraumatic stress disorder (PTSD) continue to suffer even with the best current medications. Progress in developing more effective medications is hampered by the substantial variability within Veterans with PTSD, meaning the most effective medication likely varies from individual to individual. New scientific tools to help identify distinct subgroups of Veterans with PTSD who are likely to respond to specific medications could help improve treatment in this population. Research has indicated that a specific subgroup of Veterans with PTSD with a high level of anxious arousal may benefit from medications which boost signaling of the neurotransmitter gamma-aminobutyric acid (GABA). This project aims to validate a clinical test to identify these individuals using new computational and neuroimaging methods combined with the medication lorazepam, a positive GABA modulator. The ultimate goal is to use these methods in future clinical trials of new medications to target the best treatments to individual Veterans with PTSD.

Do I need to stop my current medications to join the trial?

You may need to stop certain medications, especially if they interact unsafely with lorazepam. However, other psychotropic medications are allowed if they are at a stable dose for at least 2 weeks and do not have unsafe interactions with the study drug.

Is lorazepam generally safe for humans?

Lorazepam, a type of benzodiazepine, is generally considered safe for humans, with adverse reactions being rare. Common side effects include drowsiness, dizziness, and nausea, but these are usually mild and occur more frequently in the first month of use. ^{1 2 3 4 5}

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

Lorazepam is a benzodiazepine primarily used for anxiety, insomnia, and other conditions, but its use for PTSD is less common compared to other treatments like phenelzine. Unlike phenelzine, which is an antidepressant, lorazepam works by enhancing the effect of a neurotransmitter called GABA, which helps calm the nervous system. ^{4 6 7 8 9}

Who Is on the Research Team?

Jonathan R Howlett, MD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Are You a Good Fit for This Trial?

This trial is for Veterans with PTSD, particularly those who experience high levels of anxious arousal. Participants must meet specific criteria that will be determined by the study's inclusion and exclusion details.

Inclusion Criteria

I have been diagnosed with PTSD recently.

Veteran

I can avoid alcohol for 24 hours before and after the test.

Exclusion Criteria

Pregnancy (assessed by urine test at time of screening and prior to administration of study medication) or lactation

I tested positive for drugs but can retake the test in 2 weeks.

Self-report or observable signs of drug or alcohol intoxication or withdrawal

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of lorazepam or placebo in a randomized crossover design, with a 1-week washout period between sessions

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lorazepam

Trial Overview The study tests whether Lorazepam, which enhances GABA neurotransmitter signaling, can help certain PTSD subgroups. It involves computational analysis and neuroimaging to identify individuals likely to benefit from this treatment.

How Is the Trial Designed?

Group I: Placebo, then lorazepam 1 mg Experimental Treatment 2 Interventions

Participants will first receive a single dose of placebo on the first testing session. After a 1 week washout period, participants will then receive a single dose of lorazepam 1 mg on the second testing session.

Group II: Lorazepam 1 mg, then placebo Experimental Treatment 2 Interventions

Participants will first receive a single dose of lorazepam 1 mg on the first testing session. After a 1 week washout period, participants will then receive a single dose of placebo on the second testing session.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a 3-year study involving a 1,000-bed teaching hospital, adverse reactions to orally administered sedative/hypnotics were found to be very rare, with a median frequency of only 0.01% (1 in 10,000 doses).

Most reported adverse reactions were mild and considered extensions of the therapeutic effects, primarily occurring in patients over 55 years old, with no cases of violent behavior or global amnesia reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse reactions to sedative/hypnotics: three years' experience. Mendelson, WB., Thompson, C., Franko, T.[2019]

Lorazepam is preferred for managing anxiety and other conditions due to its simpler metabolism, fewer drug interactions, and lower risk of adverse reactions, making it safer for patients with hepatic and renal impairments.

During the lorazepam shortage, midazolam has been identified as an effective alternative for off-label uses, but clinicians should use caution with conversion guidelines and start with lower doses to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surge of Midazolam Use in the Midst of Lorazepam Shortage. Liu, TT., Frost, ED., Donlon, J., et al.[2023]

In a four-week double-blind study involving 68 adult outpatients, lorazepam demonstrated significant efficacy in reducing neurotic anxiety symptoms compared to placebo, as shown by improvements on multiple anxiety rating scales.

The treatment was well-tolerated, with no significant changes in vital signs or laboratory values, and only one mild side effect (urinary retention) that resolved without stopping the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical assessment of the safety and efficacy of lorazepam, a new benzodiazepine derivative, in the treatment of anxiety. Pinosky, DG.[2013]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative safety of benzodiazepines and opioids among veterans affairs patients with posttraumatic stress disorder. [2022]

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

Adverse reactions to sedative/hypnotics: three years' experience. [2019]

3. Canada pubmed.ncbi.nlm.nih.gov

Acute adverse event signalling scheme using the Saskatchewan Administrative health care utilization datafiles: results for two benzodiazepines. [2013]

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

Surge of Midazolam Use in the Midst of Lorazepam Shortage. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacotherapy of 1,044 inpatients with posttraumatic stress disorder: current status and trends in German-speaking countries. [2022]

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

Posttraumatic stress disorder in Israeli combat veterans. Effect of phenelzine treatment. [2019]

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

Clinical assessment of the safety and efficacy of lorazepam, a new benzodiazepine derivative, in the treatment of anxiety. [2013]

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

Deimplementation of Benzodiazepine Prescribing in Posttraumatic Stress Disorder in the Veterans Health Administration. [2022]

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

Lorazepam, a new benzodiazepine derivative, in the treatment of anxiety: a double-blind clinical evaluation. [2013]