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

Trial Summary

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.

How does L-methylfolate differ from other treatments for Generalized Anxiety Disorder?

L-methylfolate is unique because it is a form of folate (a type of B vitamin) that can cross the blood-brain barrier and is thought to enhance the production of neurotransmitters like serotonin, norepinephrine, and dopamine, which are important for mood regulation. Unlike standard anxiety medications, it may also help reduce inflammation and support neural health, making it a novel option for those with anxiety potentially linked to folate metabolism issues. ^{1 2 3 4 5}

What is the purpose of this trial?

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 generalized anxiety disorder (GAD). The primary objective is to monitor for side effects and other risks associated with the treatment. Secondary objectives are to compare the severity of symptoms, serum levels of folate, vitamin B12, C-reactive protein, homocysteine, tumor necrosis factor alpha and interleukin 6 before and after treatment. Participants will continue with their usual treatment for GAD and receive add on treatment with L-methylfolate 15 mg per day for 8 weeks. All participants will receive the same intervention.

Eligibility Criteria

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

Reading competence below Grade 5

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

References

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

Folinic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory depression. [2022]

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

L-methylfolate Plus SSRI or SNRI from Treatment Initiation Compared to SSRI or SNRI Monotherapy in a Major Depressive Episode. [2021]

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

Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD. [2021]

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

Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study. [2022]

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

L-Methylfolate For Bipolar I depressive episodes: An open trial proof-of-concept registry. [2019]