The apolipoprotein E 4 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 4 allele influences response in geriatric depression to mirtazapine and paroxetine, two frequently prescribed antidepressants. We hypothesized that 4 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 4 allele showed a rapid onset of mirtazapine action, whereas paroxetine-treated patients with the 4 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 4 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.