Does L-Methylfolate Help SSRI-Resistant Depression?
Does L-Methylfolate Help SSRI-Resistant Depression?
Yes. Adding 15 mg daily of l-methylfolate to SSRI antidepressants significantly improves response rates in patients with treatment-resistant major depression. Two randomized controlled trials found that l-methylfolate augmentation doubled response rates from 15 percent to 32 percent compared to continuing SSRI medication alone. The benefits appeared within 30 days of starting treatment, with a number needed to treat of 6 patients.
L-methylfolate is the only form of folate that crosses the blood-brain barrier and plays a crucial role in producing neurotransmitters like serotonin, dopamine, and norepinephrine. When people have low folate levels in their brain, they cannot efficiently make these mood-regulating chemicals, which may explain why some patients don’t respond well to SSRI medications that work by increasing these same neurotransmitters.