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.
Brown
E Sherwood
ES
Psychoneuroendocrine Research Program, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-8849, USA. sherwood.brown@utsouthwestern.edu
Stuard
Gary
G
Liggin
Joshua D M
JD
Hukovic
Nedim
N
Frol
Alan
A
Dhanani
Nafisa
N
Khan
David A
DA
Jeffress
Jala
J
Larkin
Gregory L
GL
McEwen
Bruce S
BS
Rosenblatt
Randall
R
Mageto
Yolanda
Y
Hanczyc
Margaret
M
Cullum
C Munro
CM
D000305:Adrenal Cortex Hormones / Q000009:adverse effects; D000328:Adult; D000339:Affect / Q000187:drug effects; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004347:Drug Interactions; D011307:Drug Prescriptions; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000503:physiopathology; D007807:Language Tests / Q000706:statistics & numerical data; D008171:Lung Diseases / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008875:Middle Aged; D019964:Mood Disorders / Q000188:drug therapy* / Q000209:etiology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010672:Phenytoin / Q000627:therapeutic use*; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000503:physiopathology; D014706:Verbal Learning / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D018501:Antirheumatic Agents; D010919:Placebos; D010672:Phenytoin