To clarify the profile of depressive symptoms in major depressive episodes in patients with Alzheimer's disease (AD-MD), we compared AD-MD with major depressive disorder in non-demented elderly patients (MDD) matched for age, using the 17-item Hamilton Rating Scale for Depression (HAM-D(17)). In addition, to clarify which depressive symptoms of AD patients respond to treatment with the selective serotonin and noradrenaline reuptake inhibitor (SNRI) milnacipran, we compared the HAM-D(17) average score and the score of each HAM-D item, the mini-mental state examination (MMSE) score, and GAF score according to the DSM-IV evaluation of AD-MD patients at baseline and at the endpoint (12 weeks). Depressive mood, loss of interest in hobbies and social activities and anxiety (psychic) scored the highest in both AD-MD and MDD groups, while psychomotor retardation scored significantly higher in AD-MD, and insomnia and anxiety (somatic) significantly did so in MDD. We also found that depressive mood, suicidal tendency, loss of interest, psychomotor retardation, anxiety (psychic), gastrointestinal symptoms, general somatic symptoms, and hypochondriasis remarkably improved in patients of AD-MD treated with milnacipran. Our results suggest that in general the profiles of depression in AD-MD and MDD are similar, despite some different clinical features between both conditions. Our study also suggests that milnacipran is promising to treat a broad range of depressive symptoms in AD-MD patients.