Using L-methylfolate to help patients with treatment-resistant anxiety

PSIY-744-23: Adjunctive Treatment With L-methylfolate for Treatment-Resistant Generalized Anxiety Disorder: a Pilot Study

Phase 4 Interventional Queen's University · NCT06218030

This study is testing if adding L-methylfolate to the usual anxiety medications can help people with treatment-resistant generalized anxiety disorder feel better.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment10 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorQueen's University Academic / other
Locations1 site (Kingston, Ontario)
Trial IDNCT06218030 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the safety and tolerability of L-methylfolate as an adjunctive treatment for patients suffering from treatment-resistant generalized anxiety disorder (GAD). Participants will continue their usual treatment with SSRIs or SNRIs while receiving 15 mg of L-methylfolate daily for 8 weeks. The study will monitor side effects and assess changes in anxiety symptoms and various biomarkers before and after treatment. The goal is to determine if L-methylfolate can enhance treatment outcomes for those who have not responded to standard therapies.

Who should consider this trial

Good fit: Ideal candidates are adults with treatment-resistant GAD who have been on a stable dose of SSRIs or SNRIs for at least 12 weeks.

Not a fit: Patients with moderate to severe major depressive disorder or significant suicidality may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new option for patients with treatment-resistant generalized anxiety disorder, potentially improving their symptoms and quality of life.

How similar studies have performed: Previous studies have shown that adjunctive folate treatments can improve outcomes in major depressive disorder, suggesting potential for success in this context as well.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Adults.
* Patients on a stable dose of an selective serotonin uptake inhibitors (SSRI) or serotonin and noradrenaline reuptake inhibitors (SNRI) for at least 8 weeks.
* Treatment-resistant GAD, defined by lack of response to at least two drugs, from two different classes of drugs considered first-line or second-line for GAD according to the Canadian Clinical Practice Guidelines for the Management of Anxiety, Posttraumatic Stress and Obsessive-Compulsive Disorders (Katzman et al., 2014). Only trials lasting at least 8 weeks and with at least the minimum effective dose of the given medication will be considered failed trials.

Exclusion Criteria:

* Patients with moderate to severe major depressive disorder based on the Patient Health Questionnaire - Nine Item (PHQ-9) scale (score of 15 or above) at baseline.
* Mini International Neuropsychiatric Interview version (MINI) 7.0 indicates moderate to high current suicidality or "suicide likely in near future" or current suicidal behavior disorder.
* Patients diagnosed with obsessive-compulsive disorder (OCD), bipolar disorder, schizophrenia, schizoaffective disorder, personality disorders, substance use disorders, intellectual disabilities, dementia, epilepsy or other severe neurological diseases.
* Patients with cardiovascular diseases, infections, inflammatory diseases, recent surgeries, recent physical trauma and other medical issues that could produce elevation of c-reactive protein (CRP) or homocysteine.
* Consumption of cannabis, any cannabis by-products, illicit drugs, or alcohol above 3 drinks per week.
* Supplementation of diet with vitamins or consumption of natural health products that may affect anxiety or depression symptoms.
* Reading competence below Grade 5.
* Participants who do not have capacity to conduct consent process.

Where this trial is running

Kingston, Ontario

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Generalized Anxiety Disordergeneralized anxiety disorderanxiety disorder
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.