Which medication had a more favorable effect on verbal working memory in treatment-resistant schizophrenia?

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Treatment efficacy in schizophrenia is typically defined by symptom reduction, but newer antipsychotic medications could also affect aspects of disability such as neurocognitive deficits. The authors evaluated risperidone’s effects on verbal working memory, which is of theoretical interest because of its link to prefrontal activity and of practical interest because of its link to psychosocial rehabilitation.

The researchers assessed verbal working memory in 59 patients with treatment-resistant schizophrenia as part of a randomized, double-blind comparison of risperidone and haloperidol. Memory was measured with and without distraction at baseline and after 4 weeks of both fixed- and flexible-dose pharmacotherapy.

Risperidone had a greater beneficial effect on verbal working memory than haloperidol across both testing conditions and both study phases. The treatment effect remained significant after controlling for benztropine cotreatment and changes in psychotic and negative symptoms. Neither benztropine status nor symptom changes were significantly related to memory performance.

The authors concluded that risperidone appeared to have a more favorable effect on verbal working memory than a conventional neuroleptic. They proposed that the benefit might be due at least partly to a direct drug effect, possibly through antagonism of the 5-HT2A receptor. They suggested that efficacy in schizophrenia pharmacotherapy could be broadened to include effects on neurocognitive abilities.