Prediction of therapeutical response to antidepressants based on pharmacological testing
Tatsiana Dakukina, T. Golubeva, Irina V. Haidukevich, M. Machrov · 2019
Objectives:Depression is often associated with folate metabolism dysfunction and subsequent hyperhomocysteinemia. On the other hand, hyperhomocysteinemia can lead to depressive-like symptoms.Background:The aim of the study was to assess the effectiveness, tolerability, and safety of L-Methylfolate as an adjuvant treatment in adults with treatment-resistant depression and homocysteinemia associated with the MTHFR C667T/u04101298u0421 or MTRR A66G genotypes.Materials and Methods:We analyzed the data of 7 patients with treatment-resistant depression (2 family cases), who failed at least 2 adequate course of antidepressant treatment and had concurrent hyperhomocysteinemia. The patients received open-label treatment with L-Methylfolate (initial dose 400-800 mg/day, according to clinical response and tolerability). The primary outcome measured with the Montgomeryu2013Asberg Depression Rating Scale (MADRS). Subjective mood evaluated with the scale at baseline and after four weeks of treatment. Data about adverse effects related to L-Methylfolate and a self-harm risk assessment were also obtained.Results and Conclusions:Over the course of treatment, all patients showed more than 50% reduction of MADRS scores. The most frequently reported adverse effects were dizziness and nausea. No serious adverse effects were observed.In the case of homocysteinemia associated with the MTHFR C667T/u04101298u0421 and MTRR A66G genotypes and treatment-resistant depression, the precursor of vitamin B9, L-Methylfolate, should be used to improve treatment outcome. Further double-blind controlled trials of L-Methylfolate treatment are needed.