B-Vitamin may benefit MDD patients with obesity and chronic inflammation

Vladimir Maletic, University of South Carolina School of Medicine, Greenville, South Carolina, and colleagues analyzed six studies. They found support for adjunctive LMF use in MDD patients not responding to antidepressant monotherapy. Treatment response was highest in patients with inflammatory biomarkers and obesity.

Major depressive disorder is a common mood disorder linked with significant disability and frequent treatment challenges. Currently, there are many options for MDD treatment, but substantial challenges persist as many patients do not respond adequately to treatment. A 2021 study reported that 30.9% of adults with MDD have treatment-resistant depression. Therefore, new therapeutic approaches are needed for MDD treatment.

The role of folate (vitamin B9) and other B vitamins has been of great interest in the pathophysiology and treatment of depression. Therefore, the authors aimed to examine the potential of using l-methylfolate as adjunctive therapy for major depressive disorder and assess its role in filling current treatment gaps for overweight/obese patients with chronic inflammation.

For this purpose, the researchers searched online databases using keywords of depression, adjunctive, and l-methyl folate to identify studies published from January 2000 to April 2021.

The research included two randomized controlled trials (RCTs), a real-world prospective study, and an open-label extension of these RCTs. Post hoc analyses that explored subgroups and their response to LMF treatment were also included with overweight patients with elevated inflammatory biomarkers.

Key findings include:

• These studies support using LMF as an adjunctive treatment in MDD patients not responding to antidepressant monotherapy.
• The most effective dose tested was 15 mg/day. Treatment response was higher in individuals with a BMI ≥ 30 kg/m2 and increased levels of inflammatory biomarkers.
• Inflammation is associated with increased production of proinflammatory cytokines, which interferes with the synthesis and turnover of monoamine neurotransmitters, thereby contributing to the expression of depressive symptomatology.
• LMF may mitigate these effects by facilitating tetrahydrobiopterin (BH4) synthesis, a critical coenzyme in neurotransmitter production.
• LMF does not cause adverse reactions commonly associated with other adjunctive MDD treatment agents (e.g., atypical antipsychotics), such as metabolic perturbations, weight gain, and movement disorders.

"Given that people with obesity and chronic inflammation may be prone to depression that is more difficult to treat and that currently available adjunctive treatment options, i.e. atypical antipsychotics have unfavourable side effect profiles, patients in this subpopulation may see additional benefit from LMF as an adjunctive treatment option for MDD that is not responsive to antidepressant pharmacotherapy," the researchers conclude.

Reference:

Maletic V, Shelton R, Holmes V. A review of l-methylfolate as adjunctive therapy in the treatment of major depressive disorder. Prim Care Companion CNS Disord. 2023;25(3):22nr03361. https://doi.org/10.4088/PCC.22nr03361