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Can Metabolic Therapy Help People with Treatment-Resistant Depression?

Research funded by the American Foundation for Suicide Prevention (AFSP) sought to answer the questions:

Are metabolic abnormalities more likely for people with treatment-resistant depression? Might they respond to metabolic treatment?

These are important questions to answer as 15% of cases of major depressive disorder are refractory to treatment. Treatment resistant depression can result in significant morbidity and mortality.

Dr. Lisa Pan of the University of Pittsburgh and her team looked at 33 patients with treatment-resistant depression and 16 healthy control patients aged 14-40 years old. After evaluation, abnormalities were found in 21 of the 33 participants in the depression group and no abnormalities were not found in the control group. The most common abnormality, found in 12 participants, was cerebral folate deficiency (CFD), a metabolite that affects nerve function. Treatment of 1-2 mg daily doses of folinic acid for six weeks to the 12 patients with CFD and treatment-resistant depression. At follow-up, 10 of the participants showed reductions in symptoms related to depression or suicidal ideation.

The main takeaway is that an evaluation of metabolites related to nervous system functioning is important for people with depression, especially those with treatment-resistant depression. Targeted metabolic therapy shows promise and with further research it may be possible to diagnose and treat these abnormalities thus revolutionizing psychiatric treatment for treatment-resistant depression.


The findings were published August 2016 in The American Journal of Psychiatry (read journal article here). An overview of the research can be found as

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