Lamotrigine Therapy and Biomarkers of Cerebral Energy Metabolism in Older Age Bipolar Depression.
Level 3 - non-randomized controlled study
Non-randomized prospective follow-up study with a healthy comparison group
PubMed 31000323 · doi:10.1016/j.jagp.2019.02.017
What was done
Researchers measured cerebral metabolites (glutamate [Glu], glutamine [Gln], and N-acetyl aspartate [NAA] as ratios to creatine [Cr]) in the anterior cingulate cortex and parieto-occipital cortex using 4-Tesla 1H-MRS. They compared 21 individuals with older age bipolar depression (mean age 62.0 ± 5.9 years) to 14 psychiatrically healthy controls (mean age 67.5 ± 8.8 years). The depressed group received 8 weeks of open-label lamotrigine monotherapy, with 1H-MRS scans and Montgomery-Asberg Depression Rating Scale evaluations performed at baseline and week 8.
What was found
At baseline, the NAA/Cr ratio was significantly lower in participants with bipolar depression by 14% (95% CI: [1%, 26%]) compared to healthy controls. No associations were observed between NAA/Cr, Glu/Cr, or Gln/Cr ratios and depression severity, nor were metabolite changes linked to lamotrigine treatment response.
Why it matters
This study provides preliminary evidence of altered cerebral energy metabolism or neuronal integrity in older age bipolar depression, while suggesting that clinical response to lamotrigine is not directly reflected in short-term alterations in these 1H-MRS metabolite ratios.
Limits
The study is limited by a very small sample size (n = 35 total), an open-label design without a randomized placebo group, and reporting of metabolite levels as ratios to creatine rather than absolute concentrations.
Cited by
- contradicts Lamotrigine treatment typically produces reductions in brain glutamate levels over a period of approximately three months.