High-dose quetiapine does not have a broad-spectrum antidepressant effect, but appears to be most effective at treating certain depressive symptoms, including lack of pleasure/interest, guilt/pessimistic thoughts, reduced sleep, reduced appetite, and anxiety/tension, which commonly co-exist in a depressive subtype known as melancholic depression. This is not surprising because melancholic depression is well-known to be responsive to medications that increase serotonin and norepinephrine neurotransmission, compared to selective serotonergic antidepressants. To the researchers knowledge, no study has examined if patients with melancholic depression at baseline are more responsive to quetiapine, although the fact that quetiapine seems to be most effective at treating symptoms common in melancholic depression, as well as the fact that quetiapine has an active metabolite nor-quetiapine with strong affinity for inhibiting norepinephrine reuptake, suggests this may be the case. Given that insomnia is considered a symptom of melancholic depression, it would also be pertinent to demonstrate that the effect of quetiapine on melancholic depression is not due to its sedating effect.