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

28 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

How does the drug Guanfacine differ from other treatments for depression?

Guanfacine is unique in its use for depression as it is primarily known for treating attention deficit hyperactivity disorder (ADHD) and hypertension (high blood pressure), working by affecting receptors in the brain that help improve attention and reduce impulsivity and hyperactivity. This mechanism of action differs from traditional antidepressants, which typically target neurotransmitters like serotonin or dopamine. ^{1 2 3 4 5}

Research Team

Laura M Hack, MD, PhD

Principal Investigator

Stanford University

Leanne M Williams, PhD

Principal Investigator

Stanford University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Nefazodone in the treatment of severe, melancholic, and recurrent depression. [2018]

2. Austria pubmed.ncbi.nlm.nih.gov

Therapeutic and side-effect profile of a selective and reversible MAO-A inhibitor, brofaromine. Results of dose-finding trials in depressed patients. [2013]

3. India pubmed.ncbi.nlm.nih.gov

Therapy with amineptine, a dopamine reuptake inhibitor, in patients with major depression. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Absolute bioavailability and electroencephalographic effects of conventional and extended-release formulations of venlafaxine in healthy subjects. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Tolerability and antidepressive effect of brofaromine, a short-acting reversible MAO inhibitor--an open study. [2019]