Are second generation antipsychotics a distinct class?

Second generation antipsychotic medications have become synonymous with "atypicality." To support the clinical lore of equivalent efficacy with reduced risk of extrapyramidal symptoms, clinical trials have overwhelmingly chosen a high-potency first-generation antipsychotic (e.g., haloperidol) as a comparator. Very few clinical trials have compared a second-generation antipsychotic with a low- or mid-potency first-generation antipsychotic medication.

We identified eight completed, published, double-blind, randomized clinical trials that compared a second-generation antipsychotic with a low- or mid-potency first-generation antipsychotic and reviewed outcome measures for efficacy and extrapyramidal symptoms; 1,241 patients were represented in these eight trials.

Although data are very limited, mid- and low-potency first-generation antipsychotics show efficacy and extrapyramidal side effects that are comparable to those of second-generation antipsychotics.

Aside from clozapine, first-generation and second-generation antipsychotics represent a diverse group of medications that have heterogenous receptor profiles and side effects but comparable clinical efficacy and potential to cause extrapyramidal symptoms. Clinicians may provide better treatment for patients by considering the unique pharmacological and side-effect profile of each particular antipsychotic independent of its classification as a first- or second-generation agent.