The Use of Genetic Testing in the Management of Depression

AIMS: We report on a case of depression where genetic testing was used to determine potential treatment modalities. METHODS: The patient is a 78-year-old man who had suffered from depression for 55 years. He had a serious episode in 2002. He developed a further depressive episode in 2018 which did not respond to paroxetine. He was offered TMS and was initially treated in the NHS and subsequently in the private sector. He went into remission with TMS and continues to remit with TMS however his depression became unstable and it was clear that the paroxetine was having no effect. He agreed to have a genetic test, a buccal mouth swab was taken and posted to gensense in the United States. An 18 page document and a half hour session with gensense are included in the cost of the test. The results of his genetic test and suggestions regarding treatment are detailed below. SLC6A4 L(G)/S serotonin transporter indicating a less favourable response to SSRI medication (20% response versus 40% response). SNRI medication may be useful. BDNF Val/Met Met carriers may have poor response to SSRIs and an improved response to SNRI's and TCA's. Met carriers have a 3 times better response to exercise than Val/Val MTHFR A/A variant, this results in a 70% reduction) in the ability to convert folate to methyl folate (required for the manufacture of serotonin). Taking L-methylfolate supplementation (7.5mg) may improve serotonin production and provide a 2 times increase in response rate to antidepressants. COMT Val/Val variant indicates improved response with brain stimulation therapy such as ECT and TMS CACNA1C A/A variant which increases the anteromedial and amygdala activity and increased neuronal activity as a result of increased calcium channel receptors. This variant is associated with more depression, OCD and anxiety. Using lithium, sodium valproate and lamotrigine could be potentially useful in this group. RESULTS: The patient's antidepressant was switched from Paroxetine to Venlafaxine XL 150 mg, he started taking L methyl folate supplements (7.5mg daily) and was put onto sodium valproate 250 mg 3 times a day. His HAM-D went from 39 in December 2022 to sub-baseline by the end of January 2023. He also started regular mild exercise and daily use of tDCS (Sooma and Flow). CONCLUSION: We conclude that genetic testing can be a useful clinical tool and can be helpful in deciding which treatments may benefit.