Antipsychotic and antidepressive effects of second generation antipsychotics: two different pharmacological mechanisms?

Second generation antipsychotics display antidepressive effects in schizophrenic patients that are more pronounced than those of traditional neuroleptics and that go beyond antidepressive effects secondary to the reduction of positive symptoms. The antidepressive potential of second generation antipsychotics is presumably related to their pharmacological mechanisms, which differ from those of traditional neuroleptics. Among others, 5-HT(2A) antagonism is of special relevance for most of the new antipsychotics in this respect. But also special interactions with the dopaminergic system, as is the case with amisulpride and aripiprazole, or noradrenalin- and/or serotonin-reuptake-inhibition, as with ziprasidone and zotepine, should be considered. It can be summarised that the antipsychotic and antidepressive effects of second generation antipsychotics are mostly based on different pharmacological mechanisms. This might be especially true for direct antidepressive effects, i. e. antidepressive effects that are not mediated by the reduction of positive symptoms.