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

Last updated: April 4, 2025
Sponsor: Kingston Health Sciences Centre
Overall Status: Active - Recruiting

Phase

4

Condition

Anxiety Disorders

Panic Disorders

Mood Disorders

Treatment

L-methylfolate

Clinical Study ID

NCT06218030
6038351
  • Ages 18-65
  • All Genders

Study Summary

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 and homocysteine 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

Inclusion

Inclusion Criteria:

  • Adults.

  • Patients on a stable dose of an selective serotonin uptake inhibitors (SSRI) orserotonin and noradrenaline reuptake inhibitors (SNRI) for at least 8 weeks.

  • Treatment-resistant GAD, defined by lack of response to at least two drugs, from twodifferent classes of drugs considered first-line or second-line for GAD according tothe Canadian Clinical Practice Guidelines for the Management of Anxiety,Posttraumatic Stress and Obsessive-Compulsive Disorders (Katzman et al., 2014). Onlytrials lasting at least 8 weeks and with at least the minimum effective dose of thegiven medication will be considered failed trials.

Exclusion

Exclusion Criteria:

  • Patients with moderate to severe major depressive disorder based on the PatientHealth Questionnaire - Nine Item (PHQ-9) scale (score of 15 or above) at baseline.

  • Mini International Neuropsychiatric Interview version (MINI) 7.0 indicates moderateto high current suicidality or "suicide likely in near future" or current suicidalbehavior disorder.

  • Patients diagnosed with obsessive-compulsive disorder (OCD), bipolar disorder,schizophrenia, schizoaffective disorder, personality disorders, substance usedisorders, intellectual disabilities, dementia, epilepsy or other severeneurological diseases.

  • Patients with cardiovascular diseases, infections, inflammatory diseases, recentsurgeries, recent physical trauma and other medical issues that could produceelevation of c-reactive protein (CRP) or homocysteine.

  • Consumption of cannabis, any cannabis by-products, illicit drugs, or alcohol above 3drinks per week.

  • Supplementation of diet with vitamins or consumption of natural health products thatmay affect anxiety or depression symptoms.

  • Reading competence below Grade 5.

  • Participants who do not have capacity to conduct consent process.

Study Design

Total Participants: 10
Treatment Group(s): 1
Primary Treatment: L-methylfolate
Phase: 4
Study Start date:
October 22, 2024
Estimated Completion Date:
May 01, 2026

Study Description

Background: Up to 33.7% of the population are affected by an anxiety disorder during their lifetime according to large populationbased surveys. Generalized anxiety disorder (GAD) has a lifetime prevalence of 2.8% to 6.2% in these studies. GAD is associated with functional, occupational, and quality of life impairments. Certain types of medications and psychotherapies are established treatments for GAD, but only 50% of the patients respond to the first treatment trial. Deficiency of folates and neuroinflammation are two hypothesis that could explain why some patients with anxiety disorders do not respond to the usual treatments. Supplementation with folates could correct these deficiencies and reduce inflammation, thus increasing the success rates for treatments. In studies with major depressive disorder, adjunctive folates were associated to higher remission rates. Other studies indicate that folate supplementation lowers homocysteine levels and inflammation. Objectives: Ascertain if adjunctive treatment with Lmethylfolate can produce improvement in treatment-resistant GAD subjects. Methods: This is a proof-of-concept pilot study, an open-label trial of adjunctive treatment with L-methylfolate in patients with treatment-resistant GAD. Ten adult patients with treatment-resistant GAD who have been on a stable dose of an SSRI or SNRI for at least 12 weeks will receive 15 mg doses of L-methylfolate daily for 8 weeks. Patients with moderate to severe major depressive disorder or suicide risk will not be included. Serum levels of folate, vitamin B12, C-reactive protein and homocysteine will be measured before and after the trial.

Connect with a study center

  • Kingston Health Sciences Centre

    Kingston, Ontario K7L 2V7
    Canada

    Active - Recruiting

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