Hello, In Methylenetetrahydrofolate reductase (MTHFR) deficiency states SSRIs are safe when taken along with L-Methylfolate supplements. Vitamin Folic acid must be converted into Dihydrofolate, Tetrahydrofolate, and then finally into the active form, L-Methylfolate (5-MTHF) by the enzyme methylenetetrahydrofolate reductase (MTHFR). In the form of L-Methylfolate, it can be transported into cells, tissues and even across the blood-brain barrier and utilized for various body functions. As per the scientific studies it is found that the efficacy of serotonin reuptake inhibitors (SSRIs) increases when taken with Folic acid in normal individuals. The MTHFR gene controls the enzymatic activity of MTHFR. In MTHFR deficiency, the individuals cannot convert folic acid to the active form L-Methylfolate. Thus taking the active form L-Methylfolate along with antidepressant medications like SSRIs can improve a person’s response to antidepressant medications like SSRIs with MTHFR deficiency. Hope I have answered your query. Let me know if I can assist you further. Regards, Dr. Mohammed Taher Ali