What is the difference between the older and newer antipsychotic medications?

Older typical or first generation antipsychotic (FGA) medications antagonize dopamine (D2) receptors, targeting positive symptoms of schizophrenia. Newer atypical or second generation antipsychotic (SGA) medications do antagonize D2, but are known as serotonin-dopamine antagonists. Primarily, serotonin antagonism targets 5HT2A, but may also include partial agonism of 5HT1A receptors. Dopamine stabilization may be achieved by some SGAs through D2 receptor partial agonism. SGAs are better equipped to target symptoms related to mood and cognition. Side effect profiles vary–FGAs have grossly more EPS and SGAs have more metabolic side effects. Overall effectiveness of all antipsychotics are similar, except for clozapine having superior efficacy.


Stahl, S. M. (2017). The prescriber’s guide: Stahl’s essential psychopharmacology (6th ed.). New York: Cambridge University Press.

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