Lorazepam for Depression and Anxiety

Overseen By Maria Ironside, DPhil

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Laureate Institute for Brain Research, Inc.

Must not be taking: Benzodiazepines, Opiates

Disqualifiers: PTSD, Schizophrenia, Bipolar, others

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: 3

165 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the anti-anxiety medication Lorazepam affects the brain's response to threats in people with depression and anxiety. Researchers aim to determine if individuals with both conditions react differently compared to those with just one. Participants will take either Lorazepam or a placebo and undergo brain scans to monitor changes. Ideal candidates include those with major depression and/or an anxiety disorder such as generalized anxiety or social phobia. As a Phase 4 trial, Lorazepam is already FDA-approved and proven effective, and this research seeks to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial allows participants to continue taking antidepressants like SSRIs, TCAs, SNRIs, and Bupropion if they haven't changed their dose or medication in the past 6 weeks. However, you cannot participate if you are currently using benzodiazepines or opiates.

What is the safety track record for Lorazepam?

Research has shown that lorazepam is generally safe for adults. One study found that a long-lasting form of lorazepam is as safe as the regular version taken several times a day. In everyday use, data from the FDA's system for reporting side effects has confirmed lorazepam's safety. However, combining lorazepam with opioids can cause serious issues, such as deep sleep and breathing difficulties. Additionally, lorazepam can be addictive, so following a healthcare provider's instructions is crucial. Despite these concerns, the FDA has approved lorazepam for treating anxiety, supporting its safe use for short periods under a doctor's care. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Lorazepam is unique because it offers a fast-acting option for tackling depression and anxiety. Unlike many standard treatments like SSRIs and SNRIs, which can take weeks to show effects, lorazepam acts rapidly, potentially providing relief in a much shorter time frame. Researchers are excited about its potential to offer quick symptom relief, which could be particularly beneficial in acute situations where immediate intervention is needed. However, it's important to consider that lorazepam is traditionally used for anxiety and its use for depression is unconventional, which is part of what makes this investigation intriguing.

What is the effectiveness track record for Lorazepam in treating depression and anxiety?

Research has shown that lorazepam effectively treats anxiety disorders. This prescription medicine reduces anxiety symptoms by calming the brain and nerves. While primarily used for anxiety, it may also benefit those with both depression and anxiety. In this trial, participants will receive either a single 1mg dose of lorazepam or a placebo, both taken orally under the supervision of a registered nurse. Real-world evidence supports the safety of this treatment. ^{1 2 3 6 7}

Who Is on the Research Team?

Maria Ironside, DPhil

Principal Investigator

Laureate Institute for Brain Research

Are You a Good Fit for This Trial?

This trial is for individuals with major depressive disorder (MDD) and/or an anxiety disorder. Participants must be fluent in English, have normal vision/hearing, and not be pregnant or planning pregnancy soon. They should not have a history of certain mental health disorders like schizophrenia or bipolar disorder, no recent medication changes, and no MRI contraindications.

Inclusion Criteria

My vision and hearing are normal, or corrected to be normal.

I am currently experiencing a major depressive episode.

MDD and AD-MDD subjects must have a minimum score of 60 on the Patient Recorded Outcomes Measurement Information System (PROMIS) Depression scale

Exclusion Criteria

I am not pregnant, breastfeeding, planning to become pregnant, or donate eggs soon.

All subjects must not be judged inappropriate for the study

All subjects must not have a risk of suicide

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2.5 hours

1 visit (in-person)

Experimental Sessions

Participants complete two identical experimental sessions, each including a 30 min eyeblink startle session and a 1.5 hr fMRI brain scan session

10 hours

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 the effects of Lorazepam versus a placebo on threat sensitivity in people with depression alone, anxiety alone, or both. It involves brain imaging to observe how different groups respond to threats after taking the drug or placebo in two sessions totaling about 10.5 hours.

How Is the Trial Designed?

Group I: Lorazepam Experimental Treatment 1 Intervention

Participants will receive a single 1mg dose of Lorazepam, to be taken orally under registered nurse (RN) supervision

Group II: Placebo Placebo Group 1 Intervention

Participants will receive a single dose of placebo, to be taken orally under RN supervision

Lorazepam is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ativan for:

• Anxiety disorders
• Short-term relief of anxiety symptoms
• Preoperative sedation

Approved in European Union as Ativan for:

• Anxiety disorders
• Insomnia
• Preoperative sedation

Approved in Canada as Ativan for:

• Anxiety disorders
• Short-term relief of anxiety symptoms
• Preoperative sedation

Who Is Running the Clinical Trial?

Laureate Institute for Brain Research, Inc.

Lead Sponsor

Trials

53

Recruited

5,400+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

California Institute of Technology

Collaborator

Trials

17

Recruited

4,300+

Published Research Related to This Trial

In a study of 112 patients with mixed anxiety and depression, both fluvoxamine and lorazepam showed significant improvements in depression and anxiety scores over 6 weeks, but lorazepam led to faster anxiety relief in elderly patients.

Fluvoxamine was associated with more nausea and vomiting, while lorazepam caused more sedation; these side effects highlight the importance of considering patient tolerance and treatment duration when choosing between these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice. Laws, D., Ashford, JJ., Anstee, JA.[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]

A review of 170 drug-impaired driving cases in Washington State found that lorazepam can significantly impair driving ability, with a mean blood concentration of 0.048 mg/L, indicating that even low levels can affect psychomotor skills.

In cases where lorazepam was the only drug detected (23 cases), the average concentration was 0.051 mg/L, reinforcing that lorazepam alone can lead to significant impairment, regardless of the concentration present.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lorazepam and driving impairment. Clarkson, JE., Gordon, AM., Logan, BK.[2019]

In a survey of 12 hospitals within the Mother-Child French-speaking Network, it was found that injectable lorazepam (IL) is only used in one hospital in France, while it is widely marketed and used in Switzerland, Canada, and Belgium for pediatric status epilepticus.

Although pharmacokinetic data suggest that IL may be preferable to injectable diazepam, there is currently no evidence proving that IL is superior in treating pediatric status epilepticus, highlighting inconsistencies in treatment protocols across different countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of injectable lorazepam in status epilepticus: a comparative study in French-speaking hospitals]. Curatolo, N., Prot-Labarthe, S., Auvin, S., et al.[2015]

Alprazolam has been found effective for treating anxiety disorders, panic disorder, and depression, showing similar efficacy to other active medications in a review of 84 studies involving 8878 patients.

The safety profile of alprazolam is comparable to that of other drugs, with infrequent reports of adverse medical events such as depression, suicidality, and withdrawal reactions, indicating it is a relatively safe option for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the safety and efficacy of alprazolam versus other agents in the treatment of anxiety, panic, and depression: a review of the literature. Jonas, JM., Cohon, MS.[2022]

In a study involving 264 patients with moderate to severe anxiety and significant depressive symptoms, lorazepam was found to be more effective than placebo in reducing anxiety severity over a four-week period.

The results showed that the differences in anxiety relief between lorazepam and placebo were both statistically and clinically significant, with no evidence of significant toxicity in either treatment group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studies with oral lorazepam in anxiety neurosis associated with depressive symptomatology. McCurdy, L., Schatzberg, AF.[2013]

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 study involving 20 patients in a psychiatric emergency service, the combination of intramuscular haloperidol and lorazepam (HDL-LZ) was found to be more effective than lorazepam alone in controlling acute agitation, with significant improvements observed 60 minutes after treatment.

Both treatment groups showed improvement over time, but the HDL-LZ group had a greater percentage of patients classified as improved, and no serious adverse effects were reported, indicating that the combination treatment is safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Bieniek, SA., Ownby, RL., Penalver, A., et al.[2013]

In a study involving 48 patients with moderate to severe anxiety due to chronic enteritis and ulcerative colitis, lorazepam was found to significantly reduce anxiety symptoms compared to placebo over a 4-week treatment period.

The treatment was well-tolerated, with infrequent side effects reported, indicating that lorazepam is a safe and effective option for managing anxiety in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lorazepam in anxiety associated with chronic enteritis and ulcerative colitis. Stokes, DK.[2013]

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LOREEV XR is not recommended in patients with a primary depressive disorder or psychosis. Preexisting depression may emerge or worsen. A possibility for suicide ...