From the Research
The major advantage of first-generation antipsychotics (FGAs) over second-generation antipsychotics (SGAs) is their lower risk of metabolic side effects, as evidenced by a recent study comparing haloperidol and olanzapine 1. This metabolic advantage makes FGAs potentially more appropriate for patients with pre-existing metabolic conditions, obesity, or those at high risk for developing these issues. The mechanism behind this difference relates to receptor binding profiles - FGAs primarily block dopamine D2 receptors, while SGAs have broader receptor activity including serotonin, histamine, and other receptors that contribute to metabolic effects. Some key points to consider when evaluating FGAs versus SGAs include:
- Lower risk of weight gain with FGAs compared to SGAs like olanzapine 1
- Higher risk of extrapyramidal symptoms (EPS) with FGAs, including akathisia, dystonia, parkinsonism, and tardive dyskinesia 2, 1
- Importance of individualizing treatment selection based on patient risk factors and treatment history 1
- Need for further research on antipsychotic selection, particularly in low- and middle-income settings 1
- Consideration of quality of life improvements with SGAs, which may be offset by metabolic side effects 3