Guanfacine for Depression

(BIG Trial)

Overseen By Laura M Hack, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Stanford University

Must not be taking: Psychotropics, CYP3A4 inhibitors

Disqualifiers: Suicidal ideations, Neurological disorders, Bipolar, Substance use, 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: 14

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test how well the medication guanfacine can help with cognitive issues in people with a specific type of depression, known as "cognitive biotype+." This kind of depression affects thinking and decision-making abilities and does not respond well to usual antidepressants. Participants will take guanfacine pills over eight weeks to determine if it improves their cognitive function and overall mental health. Those with ongoing depression, who struggle with cognitive tasks, and have not used guanfacine before might be a good fit for this study. As a Phase 4 trial, guanfacine is already FDA-approved and proven effective, and this research helps to understand how it benefits more patients.

Will I have to stop taking my current medications?

If you are currently taking psychotropic medications (drugs that affect your mood, thoughts, or behavior), you may need to stop them to join the trial, but only if your doctor agrees and they can be safely tapered off. You must wait for a period of time (5 half-lives of the medication) before starting the trial. If you are taking certain antibiotics, antifungals, or other specific medications, you may also need to stop those.

What is the safety track record for guanfacine?

Research shows that guanfacine, the drug used in this study, is generally safe for people. Previous studies have primarily examined guanfacine extended-release for treating ADHD, a condition affecting attention and behavior. These studies found that most side effects are mild to moderate, meaning they aren't too serious for most people.

In long-term studies, no major safety issues were reported for adults using guanfacine extended-release. Although this study uses guanfacine immediate release, the safety information from the extended-release version provides insight into its general safety.

Guanfacine already has FDA approval for other conditions, indicating that many people can use it without problems. However, like any medication, it's important to monitor for side effects and report them to the study team. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for depression, which often include serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), guanfacine is unique because it targets the brain’s alpha-2 adrenergic receptors. This different mechanism of action may help address symptoms of depression in a new way, potentially offering relief for those who haven't responded well to traditional antidepressants. Researchers are excited about guanfacine because it offers a fresh approach to managing depression and could lead to more personalized treatment options for patients.

What evidence suggests that guanfacine might be an effective treatment for depression?

Research has shown that guanfacine, which participants in this trial may receive, may help with mood-related symptoms by acting like an antidepressant. It appears to work by reversing certain brain signals linked to depression. Studies also suggest that guanfacine can reduce hyperactivity and impulsiveness, potentially improving thinking and focus. Additionally, guanfacine is generally considered safe with few side effects, making it a reliable option. While primarily used for ADHD, guanfacine's effect on brain functions related to thinking and control might assist with cognitive issues in depression. ^{5 6 7 8 9}

Who Is on the Research Team?

Laura M Hack, MD, PhD

Principal Investigator

Stanford University

Leanne M Williams, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Fluent and literate in English, and show non-impaired intellectual abilities to ensure adequate comprehension of the task instructions

Score > 14 on the Hamilton Depression Rating Scale 17

Meet DSM-5 diagnostic criteria for current, past, or recurrent nonpsychotic major depressive disorder established by MINI Plus

Exclusion Criteria

I have no history of illnesses or injuries that affect my thinking or memory.

I am currently taking medication for mental health, but can stop if needed.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 visits

3 visits (in-person)

Treatment

Participants receive guanfacine immediate release (GIR) for 8 weeks, with monitoring for changes in symptoms, function, and suicidality, adherence to GIR, and adverse events.

8 weeks

10 visits (5 in-person or virtual with clinician, 5 with research coordinator)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person or virtual)

Optional Extension

Participants may continue GIR if their psychiatrist or PCP is willing to prescribe it, otherwise they will be tapered off.

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Guanfacine Pill
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Guanfacine Treatment Group Experimental Treatment 1 Intervention

Participants will be prescribed tabs containing guanfacine immediate release (GIR) to be taken for 8 weeks and will be monitored by one of the study psychiatrists/nurse practitioners. Subjects will start with 0.5mg GIR nightly and increase by 0.5mg every 3 days with a goal dose of 2mg.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

Nefazodone, an antidepressant, was effective in treating patients with moderate to severe depression, including those with melancholic features and recurrent episodes, based on a pooled analysis of four placebo-controlled studies involving 664 participants.

The studies showed that nefazodone improved depression symptoms significantly, as measured by the Hamilton Rating Scale for Depression and the Clinical Global Impressions scale, indicating its efficacy across clinically important subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nefazodone in the treatment of severe, melancholic, and recurrent depression. Marcus, RN., Mendels, J.[2018]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0924977X14002788

Efficacy and safety of extended-release guanfacine ... This study demonstrates a positive risk-benefit profile in the treatment of children and adolescents with ADHD with GXR doses of up to 7 mg (0.05–0.12 mg/kg/day) ...

2. psychiatrist.com psychiatrist.com/jcp/guanfacine-extended-release-improves-adhd-symptoms-in-japanese-adults/

Efficacy and Safety of Guanfacine Extended-Release in the ... Results: Compared with placebo, there was statistically significantly greater improvement in ADHD-RS-IV total score reduction with GXR (least ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4561580/

Antidepressant-like effects of guanfacine and sex-specific ... Guanfacine has a robust antidepressant-like effect and can reverse a depression-like state induced by increased ACh signaling. These data suggest that different ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8123957/

Evaluating Guanfacine Hydrochloride in the Treatment of ... Therefore, the study concluded that GXR appears to be safe and effective for reducing hyperactivity, impulsiveness, and distractibility in ...

5. psychiatryonline.org psychiatryonline.org/doi/full/10.1176/appi.ajp.158.7.1067

A Placebo-Controlled Study of Guanfacine in the Treatment ... Guanfacine was associated with insignificant decreases in blood pressure and pulse. CONCLUSIONS: Guanfacine appears to be a safe and effective treatment for ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7531113/

Safety and efficacy of guanfacine extended-release in ... There were no major safety concerns during long-term GXR administration in adults with ADHD. After long-term treatment, patients had significant improvements ...

7. fda.gov fda.gov/media/164281/download

Intuniv Pediatric Safety and Utilization Review The majority of the U.S. FAERS reports with serious, unlabeled adverse events in the time period reviewed were pediatric patients 6-12 years old ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2935643/

Guanfacine Extended-Release Tablets (Intuniv), a ... An eight-week, multicenter, randomized, double-blind, placebo-controlled safety and efficacy study of guanfacine ER was conducted in 345 patients from 6 to 17 ...

9. link.springer.com link.springer.com/article/10.1007/s00787-018-1113-4

Long-term safety and efficacy of guanfacine extended ... In this study, treatment failure occurred in 64.9% of participants withdrawn to placebo compared with 49.3% of those who were maintained on GXR ...