Maximizing response to first-line antipsychotics in schizophrenia

The choice of first-line antipsychotic treatment for patients with schizophrenia should balance considerations of differential efficacy of antipsychotics against the relative risk of different side effects. In terms of efficacy, recent meta-analyses have shown that antipsychotics are not equivalent in efficacy. Clozapine, amisulpride, olanzapine, and risperidone show small to moderate, but statistically significant, differences, indicating greater efficacy compared to a number of other antipsychotics on some primary efficacy outcome measures. Amisulpride and cariprazine have the strongest evidence for greater efficacy for treating negative symptoms relative to other antipsychotics. In terms of side effects, clozapine and olanzapine have among the highest weight gain potential and amisulpride has more effects on QTc prolongation and prolactin elevation than other commonly used antipsychotics. Adjunctive treatment with an antidepressant drug may improve response in patients with schizophrenia who also have severe depressive or negative symptoms. For a patient with an inadequate response to an adequate dose and duration of the initial antipsychotic choice, switching to another antipsychotic with a different receptor profile may improve response, although evidence is limited. There is little evidence to support using doses above the therapeutic range other than in exceptional circumstances.