Magnetic Resonance Spectroscopy Imaging of the Effects of treatment of TBI Depression: Lessons Learned

Background: Major depression is a common complication following traumatic brain injury. It is associated with poor global clinical and psychosocial outcomes. Even though there are several studies on risk factors for major depression after TBI (henceforth will be referred to as TBI depression) there is minimal literature on the treatment of TBI depression. Further, the neurobiological changes associated with treatment have not been a focus of study. Aims: (1) To determine the effectiveness of escitalopram for the treatment of TBI depression as assessed by the Montgomery Depression H1 or proton before rating Scale (MADRS) and Clinical Global Impression-Improvement (CGI-I) scale. (2) To determine differences in brain metabolite ratios as measured by single voxel magnetic resonance spectroscopy (MRS) and multi slice magnetic resonance spectroscopy imaging (MRSI) before and after treatment with escitalopram. Methods: Double-blind, randomized controlled trial. Subjects were randomized to either the escitalopram or the placebo group. Escitalopram was started at 10mg per day and increased to 20 mg if deemed clinically necessary, at week 4. No medication changes were made after week 8. The placebo group received a pill which appeared similar to the 10 and 20 mg of escitalopram. All subjects had a total of 4 visits: baseline evaluation and follow-up visits at weeks 4, 8 and 12. All subjects underwent brain MRS/MRSI scans before (Week 1) and after treatment (week 12). Results: At the end of 12 weeks of intervention, no statistically significant differences were found between the drug and placebo groups on the MADRS or the CGI-I scale scores. There were also no statistically significant differences between the two groups on the brain metabolite ratios. However, there was a trend towards statistical significance (p value =<0.1) in escitalopram compared to placebo group after treatment. In the escitalopram compared to placebo groups, changes before to after treatment were observed. Higher Cho/Cr ratios in the right frontal cortex (median values: -0.08 versus 0.13; p values =0.08), higher NAA/Cr ratios in the right thalamus (median values: -0.12 versus 0.19 p-value=0.09), higher NAA/Cho ratios (median values: -0.40 versus -0.02; p-value = 0.06), lower NAA/Cr ratio (median values: 0.28 versus -0.38; p-value = 0.06) and lower Cho/Cr ratio (median values: 0.23 versus -0.09; p-value = 0.06) in the left frontal cortex Conclusion: These preliminary findings support the further investigation of changes in brain metabolites before and after treatment with antidepressants using larger sample sizes and strategies to reduce or eliminate artifacts in magnetic resonance imaging. Such neuro imaging studies have the potential to provide an understanding of biological mechanisms of TBI depression.