What side effects are associated with this type of intervention?

Common treatments for depression, such as SSRIs and SNRIs, have a range of side effects. SSRIs (e.g., fluoxetine, sertraline) often cause gastrointestinal issues, sleep disturbances, sexual dysfunction, and increased risk of suicidality in younger populations. SNRIs (e.g., venlafaxine, duloxetine) can lead to similar side effects, along with increased blood pressure and heart rate. Atypical antidepressants like bupropion may cause insomnia, dry mouth, and increased anxiety, while mirtazapine is associated with weight gain and sedation. Guanfacine, an Alpha-2A Adrenergic Receptor Agonist, may cause side effects such as drowsiness, low blood pressure, and dry mouth.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of depression, including selective serotonin reuptake inhibitors (SSRIs) like fluoxetine and escitalopram, and serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine. These medications have been shown to be effective in reducing depressive symptoms. While Guanfacine, an Alpha-2A Adrenergic Receptor Agonist, is being studied for its potential in treating depression, it is not yet FDA-approved for this indication. The focus on neural circuit dysfunction in depression represents a novel approach compared to traditional antidepressants.

What other types of research exist?

Promising novel alternatives to Guanfacine for depression treatment in 2024 include LY2216684, a highly selective norepinephrine reuptake inhibitor, and emerging treatments targeting specific neural circuits, such as those identified through functional magnetic resonance imaging (fMRI) studies. Additionally, SSRIs and SNRIs like paroxetine, venlafaxine, and duloxetine continue to show efficacy and may be considered based on individual patient profiles.

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Alpha-2 Adrenergic Agonist

Guanfacine for Depression (BIG Trial)

Phase 4

Recruiting

Research Sponsored by Stanford University

Eligibility Criteria Checklist

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

Must have

18-65 years of age (inclusive)

Medication naïve to guanfacine

Must not have

Current use of a strong CYP3A4 inhibitor or inducer

Severe impediment to vision, hearing and/or hand movement, likely to interfere with ability to complete the assessments, or are unable and/or unlikely to follow the study protocols

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 4 weeks, 6 weeks

Awards & highlights

Drug Has Already Been Approved

All Individual Drugs Already Approved

Pivotal Trial

Summary

This trial tests guanfacine, a drug commonly used for ADHD and high blood pressure, to see if it can help adults with certain types of depression. The study focuses on people whose depression might be due to problems in brain areas that control thinking and decision-making. Guanfacine aims to improve these brain functions, potentially offering a new treatment option for this group.

Who is the study for?

This trial is for adults aged 18-65 with major depression, who perform poorly on certain memory tasks and have specific brain activity patterns. They must not be pregnant, using psychotropic drugs without a washout period, or have metal in their body that affects MRI scans. People with recent substance abuse, PTSD, OCD, severe mental disorders like bipolar or schizophrenia are excluded.

What is being tested?

The study tests guanfacine's effect on a type of major depression linked to cognitive control issues. Participants will either receive guanfacine or a placebo. Their brain function is monitored via fMRI to see if the drug improves symptoms compared to no active treatment.

What are the potential side effects?

Guanfacine may cause side effects such as drowsiness, low blood pressure, slow heart rate and possibly fainting. It might also interact with other medications affecting liver enzymes.

Eligibility Criteria

Inclusion Criteria

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

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I am between 18 and 65 years old.

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I have never taken guanfacine before.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently taking medication that strongly affects liver enzyme levels.

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I have severe issues with vision, hearing, or hand movement that could prevent me from following study instructions.

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I have never been diagnosed with bipolar disorder, eating disorders, ADHD, schizophrenia, or psychosis.

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I have been diagnosed with PTSD or OCD according to DSM-5.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 4 weeks, 6 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~4 weeks, 6 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 4 weeks, 6 weeks 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 dorsolateral prefrontal cortex (DLPFC) activity

Secondary study objectives

Change in digit span task performance

Change in maze task performance

Change in verbal memory recognition task performance

Other study objectives

Change in Barratt Impulsiveness Scale (BIS) score

Change in Beck Anxiety Inventory (BAI)

Change in Beck Depression Inventory (BDI)

+19 more

Awards & Highlights

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Guanfacine Treatment GroupExperimental Treatment1 Intervention

Participants will be prescribed tabs containing guanfacine immediate release (GIR) to be taken for 4 weeks and will be monitored by one of the study psychiatrists. Subjects randomized to GIR will start with 0.25mg GIR upon waking and increase by 0.25mg every other day with a goal dose of 2mg.

Group II: Placebo GroupPlacebo Group1 Intervention

Participants will be prescribed tabs containing placebo to be taken for 4 weeks and will be monitored by one of thestudy psychiatrists. Subjects randomized placebo will be asked to follow the same pill regimen as subjects randomized to treatment.

0 / 6Eligibility 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 depression include Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), which work by increasing the levels of serotonin and norepinephrine in the brain, respectively. These neurotransmitters are crucial for mood regulation. Guanfacine, an Alpha-2A Adrenergic Receptor Agonist, targets a different mechanism by modulating the adrenergic system, which can influence cognitive control and emotional regulation. Understanding these mechanisms is vital for patients as it helps tailor treatments to their specific neurochemical imbalances, potentially improving efficacy and reducing side effects.

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