Attenuation of amygdala atrophy with lamotrigine in patients receiving corticosteroid therapy

BACKGROUND: Excessive corticosteroid exposure is associated with atrophic effects on the human hippocampus and amygdala. These effects seem to be, at least in part, mediated through corticosteroid-induced release of glutamate. We previously reported that lamotrigine, a glutamate release inhibitor, significantly improved declarative memory but did not change hippocampal volume, as compared with placebo, in corticosteroid-treated patients. To our knowledge, no data are available on preventing or reversing the impact of corticosteroids on the amygdala. METHODS: We examined the effects of 24 weeks of randomized placebo-controlled lamotrigine therapy on amygdala volume and mood in 28 corticosteroid-treated patients (n ≤ 12, placebo; n ≤ 16, lamotrigine). Amygdala volumes were measured from tracings of the magnetic resonance images from weeks 0 and 24. Mood was assessed every 2 weeks with the Hamilton Depression Rating Scale and the Young Mania Rating Scale. RESULTS: An analysis of covariance revealed that patients on lamotrigine had significantly larger left amygdala volume at week 24 than patients on placebo after controlling for baseline volume. Neither exit nor week 24 analysis of covariance of Hamilton Depression Rating Scale and Young Mania Rating Scale revealed a significant difference between lamotrigine and placebo groups. CONCLUSIONS: Results suggest that lamotrigine attenuated the effects of corticosteroids on the left amygdala. Larger trials are warranted to confirm these findings.