Background Excessive corticosteroid exposure is associated with atrophic effects on the human hippocampus and amygdala. These effects appear 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 to 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 for placebo, n = 16 for lamotrigine). Amygdala volumes were measured from tracings of the MR images from weeks 0 and 24. Mood was assessed every two weeks with Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS). Results An ANCOVA 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 ANCOVAs of HAM-D and YMRS revealed 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.
Corticosteroids are commonly associated with changes in mood, memory, and the hippocampus. Declarative memory decline occurs rapidly after corticosteroid administration. Minimal research has focused on interventions to prevent or reverse corticosteroid effects on the human brain and associated adverse psychiatric effects. Acetaminophen has neuroprotective properties in animal models. We examined acetaminophen add-on therapy in patients prescribed corticosteroids. Thirty outpatients prescribed oral high-dose prednisone therapy for asthma (n = 28) or allergic rhinitis (n = 2) were randomized to approximately 7 days of acetaminophen (4000 mg/day) or placebo in a double-blind fashion at the same time as prednisone. Mood was assessed with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Activation subscale of the Internal State Scale. Memory was assessed with the Rey Auditory Learning Test and asthma symptoms with the Asthma Control Questionnaire. Between-group differences were assessed using mixed ANCOVAs and within-group changes were examined with paired t-tests. Baseline mean depression scores were elevated. In the total sample, depressive and asthma symptoms improved significantly, while declarative memory worsened during prednisone therapy. No between treatment-group differences were found in mood or memory measures. Change in asthma symptoms with receiving prednisone was not related to change in mood or memory. Prednisone therapy was associated with a reduction in depressive symptom severity and decline in declarative memory that was not related to changes in asthma symptoms. This is consistent with prior research suggesting that prednisone impairs memory and may have antidepressant properties. Acetaminophen did not attenuate corticosteroid-induced mood or memory changes.
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