Abstract
Background
Patients vary in response to antidepressant medications. Apolipoprotein E (APOE) genotype
affects vulnerability to stress and risk for cognitive impairment. We sought to determine
if the APOE ε4 allele influences response in geriatric depression to mirtazapine and
paroxetine, two frequently prescribed antidepressants. We hypothesized that ε4 carriers
would show impaired antidepressant response.
Methods
The study was a double-blind, randomized, 8-week trial with a 16-week extension phase
involving 246 cognitively intact patients aged 65 years or older with major depression.
Patients were treated with mirtazapine 15–45 mg (n = 124) or paroxetine 20–40 mg (n = 122). The outcome measures were the Hamilton Depression Rating Scale, the Geriatric
Depression Scale, and the Clinical Global Impression Scale. APOE genotype was determined
by restriction isotyping.
Results
Patients carrying the ε4 allele showed a rapid onset of mirtazapine action, whereas
paroxetine-treated patients with the ε4 allele were slow to respond. This difference
could not be attributed to dosage, compliance, severity of adverse events, ethnicity,
baseline depression or cognition, gender, or age.
Conclusions
The APOE ε4 allele may affect antidepressant treatment outcome, but the effect depends
on the medication. Further studies should determine if this result applies to other
samples and medications.
Keywords
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Article info
Publication history
Accepted:
January 24,
2003
Received in revised form:
January 17,
2003
Received:
October 17,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
