....the findings of Ho and colleagues, in concert with those of the aforementioned animal studies and prior reports in humans,8 raise the important question of the clinical significance of the observed brain volume changes. Do the reductions in brain volume associated with antipsychotic medications impair function or are they related to the therapeutic benefits of these medications? Many individuals with schizophrenia discontinue taking typical and antipsychotic medications because of limited efficacy and poorly tolerated adverse effects.9 The observation by Ho and colleagues that the amount of antipsychotic treatment predicted the degree of brain volume reduction leaves open the possibility that the patients who benefitted the most continued to receive antipsychotic treatment and subsequently had the greatest brain volume changes. The idea that strategic reductions in brain volume can be functionally beneficial is supported by the improvements in cognitive capacity that accompany cortical gray matter volume reductions during adolescence.10 Alternatively, as suggested by Ho and colleagues, perhaps antipsychotic medications improve symptoms and contribute to progressive brain tissue reductions through different actions on separate brain circuits.

A classic maxim in clinical medicine is to treat the patient, not the laboratory test—or in this case, the MRI. Thus, the findings of Ho and colleagues should not be construed as an indication for discontinuing the use of antipsychotic medications as a treatment for schizophrenia. But they do highlight the need to closely monitor the benefits and adverse effects of these medications in individual patients, to prescribe the minimal amount needed to achieve the therapeutic goal, to consider the addition of nonpharmacological approaches that may improve outcomes,11 and to continue the pursuit of new antipsychotic medications with different mechanisms of action and more favorable benefit to harm ratios.