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?

This trial tests lorazepam, a medication that may help treat PTSD (posttraumatic stress disorder) in Veterans experiencing high levels of anxious arousal. Researchers aim to determine if lorazepam can identify Veterans who might benefit from this treatment by enhancing GABA, a brain chemical that calms the nervous system. Participants will take lorazepam and a placebo (a fake pill) in two different sessions to compare effects. Veterans with PTSD who often feel anxious and meet specific health criteria might be suitable for this study. As a Phase 4 trial, lorazepam is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

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.

What is the safety track record for lorazepam?

Research has shown that lorazepam, a medication often used to treat anxiety, has mixed safety results. Lorazepam is a benzodiazepine that helps with anxiety by affecting a brain chemical called GABA. However, for veterans with PTSD, drugs like lorazepam may not always be safe or effective.

Some studies indicate that many people taking lorazepam experience serious side effects, including worsened PTSD symptoms and other negative effects. Due to these risks, guidelines often advise against using benzodiazepines for veterans with PTSD. The use of these medications in this group has decreased over the years due to safety concerns.

While lorazepam is approved for anxiety, its use for PTSD requires careful consideration. Always consult a healthcare provider about the risks and benefits before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for PTSD, like SSRIs and SNRIs, work by altering neurotransmitters in the brain over several weeks. However, lorazepam offers a potentially faster-acting alternative by targeting GABA receptors, which can quickly calm the nervous system and reduce anxiety symptoms. Researchers are excited about lorazepam because it could provide rapid relief during acute stress episodes, offering a short-term solution that supplements longer-term therapies.

What is the effectiveness track record for lorazepam in treating PTSD?

Research has shown that lorazepam, a medication that boosts a brain chemical called GABA, has been considered for treating PTSD, though results are mixed. One study suggested lorazepam might help reduce intrusive thoughts, common in PTSD. However, a review of several studies found that drugs like lorazepam are generally not effective for PTSD overall, with risks often outweighing benefits. Additionally, the use of these drugs in Veterans Affairs has significantly declined over the years, reflecting doubts about their effectiveness for PTSD. Despite this, lorazepam may still provide short-term relief for certain symptoms in some people. In this trial, participants will receive lorazepam and a placebo in different sequences to evaluate its effects. ^{2 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

Participants must be able to participate and willing to give written informed consent and to comply with the study restrictions

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

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 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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26164054/

Benzodiazepines for PTSD: A Systematic Review and Meta ... Results: BZDs are ineffective for PTSD treatment and prevention, and risks associated with their use tend to outweigh potential short-term benefits. In addition ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3843020/

Anti-Intrusion Effect of Lorazepam: An Experimental Study - PMC Results from the current study suggest the possibility of lorazepam as a candidate anti-intrusion drug and the cautious use of diazepam in the treatment of PTSD ...

3. ptsd.va.gov ptsd.va.gov/professional/treat/txessentials/benzos_va.asp

Use of Benzodiazepines for PTSD in Veterans Affairs The proportion of Veterans with PTSD prescribed benzodiazepines in VA declined from 31.3% in 2009 to 10.7% in 2019, with a marked decrease after 2013, when VA ...

4. psychiatrist.com psychiatrist.com/jcp/benzodiazepines-reduce-effectiveness-exposure-therapy/

Do Benzodiazepines Reduce the Effectiveness of ... Prior data and theory suggest that these medications may inhibit response to exposure therapy, one of the most effective PTSD treatments.

5. academic.oup.com academic.oup.com/ajhp/article/82/3/e166/7848940

Characteristics of incident benzodiazepine recipients among ... Prevalent benzodiazepine prescribing in the VHA among veterans with PTSD decreased from 27.4% in 2012 to 7.6% in 2022, and incident prescribing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11622250/

Adverse event profile of lorazepam - PubMed Central In addition, the outcomes of lorazepam treatment can be less than favorable, with a notable percentage of cases resulting in death (12.4%), life ...

7. ptsd.va.gov ptsd.va.gov/professional/articles/article-pdf/id37919.pdf

Declining Benzodiazepine Use in Veterans With Posttraumatic ... * Benzodiazepine use among veterans with posttraumatic stress disorder remains above 30% and presents an opportunity for further improvement in prescribing.

8. mdpi.com mdpi.com/2077-0383/9/11/3492

An Emulation of Randomized Trials of Administrating ... In addition to worsened PTSD outcomes, several studies within the meta-analysis showed those who took benzodiazepines had an increased ...

9. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.ps.201200267

Patient and Facility Characteristics Associated With ... Guideline recommendations against benzodiazepine use by veterans with PTSD are fundamentally related to safety and secondarily to a lack of demonstrated ...