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

Abstract

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.

Psychiatric complications of treatment with corticosteroids: Review with case report

“…Valproate has been reported to prevent steroid‐induced psychosis in one case 112 . In a double‐blind, placebo‐controlled trial of 30 patients, acetaminophen 4000 mg/day did not differ from placebo with respect to change in depressive symptoms 124 …”

Hepatocyte Nuclear Factor 4 Alpha Is a Key Factor Related to Depression and Physiological Homeostasis in the Mouse Brain

“…This appears to coincide with emergence of depressive states in patients treated with corticosteroids or interferon therapy [16–18]. Moreover, coagulation dysfunction may also exert a causal effect on the development of MDD, as MDD often develops after cardiac or cerebral infarction, and anticoagulant treatments are effective in such cases, even alleviating comorbid MDD [19–21]. In contrast, MDD may have a crucial impact on the short- and long-term outcomes of these infarction diseases, with significantly higher mortality in patients with MDD [19].…”

Strategies to prevent the neuropsychiatric side-effects of corticosteroids

“…Paracetamol has been shown not to be effective in a small randomized controlled trial by Brown et al [33]. Paracetamol has been thought to be neuroprotective [45], but this does not translate into a clinically detectable difference.…”

“…There are examples of the same agents being used in the transplant population [20,21]. This article presents a case report with review of the literature regarding strategies, pharmacological (Tables 1 and 2) [22][23][24][25][26][27][28][29][30][31][32][33] and nonpharmacological, to prevent these complications. This article presents a case report with review of the literature regarding strategies, pharmacological (Tables 1 and 2) [22][23][24][25][26][27][28][29][30][31][32][33] and nonpharmacological, to prevent these complications.…”