Randomized, double-blind, placebo-controlled trial of acetaminophen for preventing mood and memory effects of prednisone bursts

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 ∼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 corticostero-idinduced mood or memory changes.