Leveraging CAM to treat depression and anxiety

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doi:10.12788/jfp.0002

Applied Evidence

Leveraging CAM to treat depression and anxiety

J Fam Pract. 2020 June;69(5):221-227 | 10.12788/jfp.0002

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References

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Adverse effects. St. John’s wort and an SSRI can lead to serotonin syndrome, which is a constellation of symptoms involving mental status changes and autonomic and neuromuscular hyperactivity caused by serotonin overactivity.¹² Furthermore, treatment failures with anticoagulants, digoxin, hormonal contraceptives, immunosuppressants, and narcotics due to concomitant use with St. John’s wort have been reported.¹³

The most common adverse reactions to St. John’s wort include gastrointestinal symptoms, dizziness, sedation, photosensitivity, dry mouth, urinary frequency, anorgasmia, and swelling.¹⁴ However, multiple studies have supported St. John’s wort to be equally or better tolerated than conventional antidepressants.^7,8

Certain forms of folate can be adjunctive treatment for depression

Methylfolate is the form of folate that crosses the blood–brain barrier. A prospective observational study evaluated the cerebral spinal fluid of 33 patients with refractory depression. The authors found metabolic abnormalities in the cerebrospinal fluid of most of those patients, the most common of which was folate deficiency in 12 patients despite normal serum folate levels.¹⁵

Additionally, current understanding of the role of the Methylenetetrahydrofolate reductase (MTHFR) gene and the folate cycle in depression supports a potential role of methylfolate in depression treatment.¹⁶ The MTHFR gene encodes for an enzyme called MTHFR. The MTHFR enzyme converts 5,10-MTHF to 5-MTHF, which then crosses the blood–brain barrier and donates a methyl group for the conversion of homocysteine to methionine. Methionine is a precursor to monoamine neurotransmitters. Thus, decreased expression of the MTHFR gene leads to decreased methylfolate levels, which, in turn, potentially leads to insufficient neurotransmitter synthesis and homocysteine excess.

MTHFR gene polymorphisms and increased homocysteine levels have been found to be associated with the occurrence of depression. One thought is that methylfolate supplementation compensates for an underlying MTHFR enzyme deficiency in patients with depression. Further studies are needed to determine if screening depressed patients for MTHFR gene polymorphisms is of benefit.¹⁶

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