The apolipoprotein E epsilon4 allele and antidepressant efficacy in cognitively intact elderly depressed patients.
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 epsilon4 allele influences response in geriatric depression to mirtazapine and paroxetine, two frequently prescribed antidepressants. We hypothesized that epsilon4 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 epsilon4 allele showed a rapid onset of mirtazapine action, whereas paroxetine-treated patients with the epsilon4 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 epsilon4 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.
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000928:Antidepressive Agents / Q000097:blood / Q000627:therapeutic use*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003071:Cognition / Q000187:drug effects*; D003863:Depression / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D005852:Geriatric Psychiatry; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use; D000078785:Mirtazapine; D009483:Neuropsychological Tests; D017374:Paroxetine / Q000097:blood / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D013997:Time Factors; D016896:Treatment Outcome
D000928:Antidepressive Agents; D001057:Apolipoproteins E; D008803:Mianserin; D017374:Paroxetine; D000078785:Mirtazapine