Do antipsychotics work in people with schizophrenia? A review of outcomes and effect sizes.

Background: The origins and treatment-target-related mechanisms of schizophrenia remain to be fully understood. Pharmacological and non-pharmacological treatments require expansion and improvements to meet peoples' needs and goals. Nevertheless, antipsychotics are a cornerstone when managing schizophrenia, being essential for reducing symptom severity, preventing relapse, improving long-term functional outcomes, and reducing premature mortality risk.

Methods: This narrative review synthesizes key evidence on the efficacy and risks associated with antipsychotic medications. The concept of effect sizes is introduced, allowing to compare antipsychotics across trials with different rating instruments and across different conditions.

Results: The available evidence in schizophrenia and comparison with medications used for medical conditions counters the sometimes-voiced criticism that antipsychotics "do not work." Instead, for a substantial group of people with schizophrenia, positive psychotic symptoms and global psychopathology improve witha small-medium effect size of about 0.4 versus placebo. These results are comparable to median effect sizes across commonly used medications for somatic disorders. When patients with initial response are continued on antipsychotics, the effect size increases to 0.9 for relapse prevention, translating into a number needed to treat (NNT) of about 3 to prevent one more relapse versus no treatment. This NNT is 10-20 times higher than that for the prevention of poor outcomes in some common medical conditions.

Conclusions: Despite general efficacy and effectiveness of antipsychotics for schizophrenia, further development is needed regarding preventive interventions and medications with mechanisms other than postsynaptic dopamine receptor blockade, with broader efficacy for positive, negative, cognitive, suicidality, and/or reward dysregulation symptomatology, and the identification of illness mechanism/biomarker-targeting treatments to enhance treatment personalization.