At low doses (e.g., 50 mg/day) quetiapine has more affinity for histamine and adrenergic receptors, the blocking of which is presumed to result in sedation. These are the doses in which quetiapine is commonly used as a sleep aid. At higher doses (150-300 mg/day) quetiapine has greater affinity for serotonin receptors and produces a greater inhibition of norepinephrine reuptake, which is believed to underlie its antidepressant effect, than it does at lower doses at which it is more likely to bind to histamine and adrenergic receptors. Not surprisingly, doses of 150-300 mg/day are recommended for the treatment of depression. It is puzzling, however, that in one trial (NCT00320268; D1448C00001, Moonstone) 50 mg/day of quetiapine was found to be just as effective as 150 and 300 mg/day as a monotherapy for patients with major depression. Although there is evidence that the antidepressant effect of high-dose quetiapine is independent of its sedating effect, to the researchers knowledge no study has adequately assessed specifically if low-dose quetiapine is an effective antidepressant in patients with depression not currently experiencing insomnia.