Changes in metabolites in the brain of patients with fibromyalgia after treatment with an NMDA receptor antagonist

Abstract

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p = 0.01) and the anterior insula (7.56 vs. 7.70; p = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p = 0.022) and the posterior insula (1.77 vs. 2.00; p = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD = 2.95 vs. 34.40, SD = 0.6; p = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD = 0.68; p = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD = 0.96 vs. 5.31, SD = 1.12; p = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

Keywords: Fibromyalgia; magnetic resonance spectroscopy; memantine.

Figure 1(a).

Voxel placement. Sagittal and coronal T1-weighted magnetic resonance imaging with the voxel placed in the (a) posterior cingulate gyrus; (b) anterior insula; (c) posterior insula; and (d) both hippocampi.

Figure 1(b).

Example of spectrum acquired with the LCModel software in the (a) posterior cingulate gyrus; (b) anterior insula; (c) posterior insula; and (d) both hippocampi with the following peaks: mI: myo-inositol; Cho: choline compounds; Cr: creatine; Glx: glutamate+glutamine+GABA; NAA: N-acetylaspartate.

Figure 2.

Box plots representing the glutamate+glutamine/creatine ratios (Glx/Cr) in the posterior insula in fibromyalgia patients who were treated with memantine for three months. Glx/Cr represents baseline values, whereas Glx/Cr2 represents post-treatment values.

Figure 3.

Box plots representing N-acetylaspartate in the left hippocampus in fibromyalgia patients who were treated with memantine for three months. NAA represents baseline values, whereas NAA2 represents the post-treatment values.