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.
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.
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.
Single group
L-methylfolate
DrugOral 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.
Incidence of treatment-emergent adverse events
Monitor participants for treatment-emergent adverse events and serious adverse events.
Incidence of treatment-emergent side effects measured with the ASEC
Monitor participants for minor treatment-emergent side effects measured with the Antidepressant Side-Effect Checklist (ASEC). ASEC is a list of 21 possible side effects from antidepressants. Each item is rated from 0 (absent) to 3 (severe).
Response to treatment defined by CGI-I score below 3
Response to treatment, which will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement (CGI-I) scale. CGI-I is a clinician administered one-item clinical scale rated from 1 (very much improved) to 7 (very much worse). Not assessed would confer score 0.
Remission defined by CGI-S score below 3
Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity (CGI-S) scale. CGI-S is a clinician administered one-item clinical scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Not assessed would confer score 0.
Change in anxiety severity measured by CGI-S
Changes in scores for CGI-S by comparing the scores in each visit. CGI-S is a clinician administered one-item clinical scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Not assessed would confer score 0.
Change of anxiety symptoms measured with GAD-7
Changes in scores for Generalized Anxiety Disorder 7-item scale (GAD-7) by comparing the scores in each visit. GAD-7 is a self-rated 7-item scale, each item is rated from 0 (not at all) to 3 (nearly every day).
Change of anxiety symptoms measured with PSWQ
Changes in scores for Penn State Worry Questionnaire (PSWQ) by comparing the scores in each visit. PSWQ is a self-rated 16-item scale, each item is rated from 1 (not at all typical of me) to 5 (very typical of me).
Click on the lead sponsor to view all of their trials.
