Effect of antipsychotic drugs on brain morphometry. A randomized controlled one-year follow-up study of haloperidol, risperidone and olanzapine

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The effect of antipsychotic drugs on brain morphology is under debate. Here we investigate the effects of risperidone, olanzapine and low doses of haloperidol on cortical and subcortical morphometry in first episode drug naïve patients with non-affective psychosis.


Morphological variables were measured in three treatment groups (haloperidol = 18; risperidone = 16; olanzapine = 18) and in healthy subjects (N = 38) at baseline and after one year. The relationship between brain morphometric changes and changes in clinical scores was also assessed.


At one year, the three antipsychotics had had an equal effect on the gray matter cortical structure, overall and lobes (all p's > 0.121.). A significant time-by-group interaction was found in lateral ventricle volume (F2,47 = 5.65; p = 0.006). Post-hoc comparisons revealed a significant increase in lateral ventricles in patients treated with risperidone (p = 0.009).


Patients exposed to atypicals (olanzapine and risperidone) exhibited a decrease in caudate nucleus volume (p = 0.001). In general, brain changes did not account in any significant manner for clinical changes over time in any treatment group.


We conclude that low doses of haloperidol, risperidone and olanzapine seem to have an equal effect on the gray matter cortical structure after 1 year of treatment. In contrast to typical antipsychotics, atypicals have differential effects on lateral ventricle and caudate nucleus volumes.

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