L-methylfolate for Generalized Anxiety Disorder

Overseen By Rafael Freire, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Queen's University

Must be taking: SSRIs, SNRIs

Disqualifiers: Major depression, Suicidality, Bipolar, Schizophrenia, 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: 4

Duration: 8 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests L-methylfolate, a form of folate, to determine its safety and effectiveness for people with generalized anxiety disorder (GAD) who haven't responded to other treatments. The trial primarily focuses on identifying side effects and safety issues. Participants will continue their usual anxiety treatment while adding L-methylfolate for 8 weeks. Suitable candidates have GAD, are on stable medication, and haven't responded to at least two types of anxiety drugs. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current medications. Participants will continue with their usual treatment for generalized anxiety disorder while receiving the additional treatment with L-methylfolate.

What is the safety track record for L-methylfolate?

Research has shown that L-methylfolate is generally safe and well-tolerated. Studies have used it alongside other treatments for various conditions without causing major side effects. For instance, one study with 68 participants found that none experienced a return of symptoms after using L-methylfolate. Additionally, it lacks the side effects often associated with other depression treatments, making it a good option for those seeking fewer side effects. While every treatment carries some risk, L-methylfolate appears to be a safe choice for many people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

L-methylfolate is unique because it offers a new approach to managing Generalized Anxiety Disorder (GAD) by targeting the underlying biochemical processes in the brain. Unlike standard treatments, which often include SSRIs or SNRIs that work by altering serotonin levels, L-methylfolate is a form of folate that crosses the blood-brain barrier and supports the production of neurotransmitters like serotonin and dopamine. This could mean fewer side effects and a more natural way to balance brain chemistry, making it an exciting potential option for those who haven't found relief with traditional medications.

What evidence suggests that L-methylfolate might be an effective treatment for generalized anxiety disorder?

Research has shown that L-methylfolate, which participants in this trial will receive, may benefit individuals with generalized anxiety disorder (GAD), particularly when other treatments have been ineffective. In past cases, individuals taking L-methylfolate reported improved sleep and reduced anxiety. This treatment can also reduce inflammation and support brain health. Studies on individuals with mood disorders have found that L-methylfolate significantly improves symptoms. It has been effective in treating depression, suggesting it might also alleviate anxiety symptoms. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Generalized Anxiety Disorder (GAD) who haven't had success with their current treatments. Participants will continue their usual GAD treatment and also take L-methylfolate.

Inclusion Criteria

I am 18 years old or older.

I have been on a stable dose of SSRI or SNRI medication for at least 8 weeks.

My anxiety hasn't improved after trying two different recommended medications for at least 8 weeks each.

Exclusion Criteria

I am unable to understand or sign the consent form by myself.

Reading competence below Grade 5

I use vitamins or natural products that might impact my anxiety or depression.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive L-methylfolate 15 mg per day for 8 weeks as an adjunctive treatment for treatment-resistant generalized anxiety disorder

8 weeks

Baseline visit, 4-week visit, 8-week visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• L-methylfolate

Trial Overview The study tests the safety and effectiveness of adding L-methylfolate to existing anxiety treatments. Patients will receive a daily dose of L-methylfolate alongside their regular medication for 8 weeks.

How Is the Trial Designed?

Group I: L-methylfolate arm Experimental Treatment 1 Intervention

Oral administration of L-methylfolate 15 mg per day for 8 weeks.

Who Is Running the Clinical Trial?

Queen's University

Lead Sponsor

Kingston Health Sciences Centre

Lead Sponsor

Trials

312

Recruited

112,000+

Queen's University

Lead Sponsor

Trials

382

Recruited

122,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06218030

NCT06218030 | Adjunctive Treatment With L-methylfolate ... The goal of this feasibility study is to determine the tolerability and safety of add on treatment with L-methylfolate in patients with treatment-resistant ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7572139/

L-Methylfolate as a Monotherapy for Treatment-Resistant ... 3/11/19, Follow-up: Pt reported improved sleep and decreased anxiety with PS 375 mg qhs and denied depression. N/A ; 4/2019. Patient continued 15 mg daily ...

3. withpower.com withpower.com/trial/phase-4-anxiety-disorders-3-2024-f66e1

L-methylfolate for Generalized Anxiety Disorder Unlike standard anxiety medications, it may also help reduce inflammation and support neural health, making it a novel option for those with anxiety potentially ...

4. psychiatrist.com psychiatrist.com/jcp/long-term-efficacy-safety-tolerability-l-methylfolate/

Long-Term Efficacy, Safety, and Tolerability of l ... Results: Of 68 subjects who met criteria for the 12-month open-label phase, 38% (n = 26) achieved full recovery, and none experienced a recurrence of MDD. For ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332221013287

The potential use of folate and its derivatives in treating ... The result demonstrated that an average improvement in depressive ratings ranging from 35% (QIDS-SR) to 55% (MADRS) and a Cohen's d ranging from 0.92 to 1.18.

6. ctv.veeva.com ctv.veeva.com/study/adjunctive-treatment-with-l-methylfolate-for-treatment-resistant-generalized-anxiety-disorder-a-pil

Adjunctive Treatment With L-methylfolate for Treatment ... The goal of this feasibility study is to determine the tolerability and safety of add on treatment with L-methylfolate in patients with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7996954/

Impact of Supplementation and Nutritional Interventions on ... L-methylfolate is generally safe and well tolerated, and lacks the side effects of other standard-of-care therapies for depression [46]. As an adjunct, L- ...