Adjunctive Treatment With L-methylfolate for Treatment-Resistant Generalized Anxiety Disorder: a Pilot Study
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: L-methylfolate.
- Who it may be relevant to
- Registry conditions: Generalized Anxiety Disorder. Basic parameters: 18 years — 65 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
PSIY-744-23: Adjunctive Treatment With L-methylfolate for Treatment-Resistant Generalized Anxiety Disorder: a Pilot Study
Overview
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.
Detailed 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, homocysteine, tumor necrosis factor alpha and interleukin 6will be measured before and after the trial.
Interventions
- Drug L-methylfolate
Oral administration of L-methylfolate 15 mg per day for 8 weeks. The study drug will be given in addition to the standard of care (SOC) for GAD.
Primary outcome measures
- Incidence of treatment-emergent adverse events [Time frame: Throughout the study, 8 weeks]
- Incidence of treatment-emergent side effects measured with the ASEC [Time frame: Baseline visit, 4-week visit and 8-week visit.]
- Response to treatment defined by CGI-I score below 3 [Time frame: 4-week visit and 8-week visit.]
Secondary outcome measures (11)
- Remission defined by CGI-S score below 3 [Time frame: 4-week visit and 8-week visit.]
- Change in anxiety severity measured by CGI-S [Time frame: Baseline visit, 4-week visit and 8-week visit.]
- Change of anxiety symptoms measured with GAD-7 [Time frame: Baseline visit, 4-week visit and 8-week visit.]
- Change of anxiety symptoms measured with PSWQ [Time frame: Baseline visit, 4-week visit and 8-week visit.]
- Change of anxiety symptoms measured with BAI [Time frame: Baseline visit, 4-week visit and 8-week visit.]
- Concentration of CRP in serum [Time frame: Baseline visit and 8-week visit.]
- Concentration of homocysteine in serum [Time frame: Baseline visit and 8-week visit.]
- Concentration of vitamin B12 in serum [Time frame: Baseline visit and 8-week visit.]
- Concentration of folate in serum [Time frame: Baseline visit and 8-week visit.]
- Concentration of tumor necrosis factor alpha in serum [Time frame: Baseline visit and 8-week visit.]
- Concentration of interleukin 6 in serum [Time frame: Baseline visit and 8-week visit.]
Eligibility 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Other
Study locations
Canada · 1 center
- Kingston Health Sciences Centre — Kingston
Publications
- Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216-26. PMID 18950248
- Saraswathy KN, Ansari SN, Kaur G, Joshi PC, Chandel S. Association of vitamin B12 mediated hyperhomocysteinemia with depression and anxiety disorder: A cross-sectional study among Bhil indigenous population of India. Clin Nutr ESPEN. 2019 Apr;30:199-203. doi: 10.1016/j.clnesp.2019.01.009. Epub 2019 Feb 12. PMID 30904222
- Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol. 2004 Jun;18(2):251-6. doi: 10.1177/0269881104042630. PMID 15260915
Identifiers
NCT: NCT06218030 · 6038351