Antipsychotic drugs for schizophrenia vary in efficacy, side effects

Antipsychotic drugs remain the standard treatment for schizophrenia, but experts flag their relative efficacy and side effects. In addition, guideline recommendations on efficacy differences are unclear, according to a study.

A total of 3,067 patients with schizophrenia (aged 18‒45 years) experiencing acute exacerbation were included in this randomized trial performed across 32 hospitals. They were randomized to 6 weeks of monotherapy with one of seven antipsychotic drugs, namely olanzapine, risperidone, quetiapine, aripiprazole, ziprasidone, perphenazine, and haloperidol.

Of the patients, 82 percent completed follow-up. In the mixed model, significant differences were noted in the percentage change in Positive and Negative Syndrome Scale (PANSS) score across the antipsychotic drugs used.

At week 6, olanzapine and risperidone demonstrated a significantly higher percentage change in PANSS score than aripiprazole, ziprasidone, and quetiapine (mean differences, 5.52‒7.03), but not haloperidol or perphenazine.

Olanzapine showed a significant association with the highest risk of weight gain (relative risk [RR], 1.44‒3.22), while aripiprazole correlated with a lower risk of hyperprolactinemia than the other antipsychotics (RR, 0.11‒0.21).

On the other hand, ziprasidone and aripiprazole correlated with reduced risks of weight gain and metabolic side effects, whereas haloperidol showed an association with an increased risk of extrapyramidal symptoms relative to other antipsychotics (RR, 0.13‒0.61).

In addition, aripiprazole was the least sedating antipsychotic drug (RR, 0.30‒0.39), while olanzapine and risperidone appeared to have lower all-cause discontinuation rates than ziprasidone and haloperidol (hazard ratio, 0.61‒0.73).

“This trial fills important knowledge gaps in acute antipsychotic treatment of schizophrenia,” the authors said. “It confirms hierarchies in efficacy and side effects of antipsychotics from related evidence.”