Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy.

BACKGROUND: In humans and animals, corticosteroid excess is associated with impairment in declarative memory and changes in hippocampal structure. In animals, phenytoin pretreatment blocks the effects of stress on memory and hippocampal histology, although no studies have examined the use of phenytoin to prevent corticosteroid-associated memory changes in humans. Mood changes are also common with corticosteroids, but few treatment data are available. This report examines whether phenytoin can prevent mood or declarative memory changes secondary to bursts of prescription corticosteroids. METHODS: Thirty-nine patients with allergies or pulmonary or rheumatologic illnesses and given systemic corticosteroid therapy were randomized to receive either phenytoin (300 mg/day) or placebo concurrently with the corticosteroids. Mood was assessed with the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Activation (ACT) subscale of the Internal State Scale; declarative memory was assessed with the Rey Auditory Verbal Learning Test (RAVLT) at baseline and after approximately 7 days of corticosteroid plus phenytoin or placebo therapy. RESULTS: The two groups were similar in age, gender, education, and corticosteroid dose. The phenytoin-treated group showed significantly smaller increases on the ACT, a mania self-report scale, than the placebo-treated group. Groups did not differ significantly on RAVLT change scores. CONCLUSIONS: This is the first placebo-controlled study to examine whether a medication can prevent mood and memory changes secondary to corticosteroids. Phenytoin blocked the hypomanic effects of prescription corticosteroids; however, phenytoin did not block the declarative memory effects of corticosteroids.

Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy.

BACKGROUND: Hippocampal volume reduction, declarative memory deficits, and cortisol elevations are reported in persons with major depressive disorder; however, data linking cortisol elevations with hippocampal atrophy are lacking. Prescription corticosteroid-treated patients offer an opportunity to examine corticosteroid effects on hippocampal volume and biochemistry and memory in humans. METHODS: Seventeen patients on long-term prescription corticosteroid therapy and 15 controls of similar age, gender, ethnicity, education, height, and medical history were assessed with magnetic resonance imaging and proton magnetic resonance spectroscopy, the Rey Auditory Verbal Learning Test, Stroop Color Word Test and other neurocognitive measures, the Hamilton Rating Scale for Depression, Young Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS: Compared with controls, corticosteroid-treated patients had smaller hippocampal volumes and lower N-acetyl aspartate ratios, lower scores on the Rey Auditory Verbal Learning Test and Stroop Color Word Test, and higher Hamilton Rating Scale for Depression and Brief Psychiatric Rating Scale scores. CONCLUSIONS: Patients receiving chronic corticosteroid therapy have smaller hippocampal volumes, lower N-acetyl aspartate ratios, and declarative memory deficits compared with controls. These findings support the idea that corticosteroid exposure appears to be associated with changes in hippocampal volume and functioning in humans.

Assessment of mood states in patients receiving long-term corticosteroid therapy and in controls with patient-rated and clinician-rated scales.

BACKGROUND: Corticosteroids have been used for many years for inflammatory diseases. Mood changes are common during short-term, high-dose, corticosteroid therapy. Virtually no data are available on the mood effects of long-term corticosteroid therapy. OBJECTIVE: To evaluate mood during corticosteroid therapy using standard clinician-rated and patient-rated measures. METHODS: Outpatients receiving prednisone therapy (7.5 mg/d for 6 months) and similar controls were enrolled. Current mood was evaluated using the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), Internal State Scale (ISS), and a diagnostic interview. RESULTS: Twenty patients and 14 controls were enrolled in the study. Depressive symptom severity as evaluated by the HRSD and ISS depression and well-being subscales and global psychiatric symptom severity as evaluated by the BPRS and ISS perceived conflict subscale were greater in patients receiving prednisone than controls. Manic symptom severity as evaluated by the ISS activation subscale but not the YMRS was higher in patients receiving prednisone. Twelve (60%) of 20 corticosteroid-treated patients met diagnostic criteria for a lifetime prednisone-induced mood disorder. Activation subscale scores did not correlate with YMRS scores. Other ISS subscales showed expected correlations with clinician-rated assessments. CONCLUSIONS: Mood symptoms and disorders are common in corticosteroid-dependent patients. Unlike short-term prednisone therapy, long-term therapy may be more associated with depressive than manic symptoms based on the clinician-rated assessments. The ISS may be more sensitive to mood symptoms with prednisone than clinician-rated scales.