Use of an acute challenge with d-amphetamine to model cognitive improvement in chronic schizophrenia

There is general agreement that pharmacologic improvement of cognition in chronic schizophrenia is a worthwhile therapeutic goal. Accordingly, there has been careful consideration about how neuropsychological methods can be used to detect improvement in cognition in people with schizophrenia. However, little data are available on the nature and magnitude of cognitive improvement that can occur with adjunctive therapeutic interventions.This double-blind, placebo-controlled crossover study examined the nature and magnitude of cognitive enhancement associated with a single-dose administration of d-amphetamine in 32 adult men with schizophrenia using a set of tasks developed specifically for detecting treatment-related change in cognitive function. Relative to placebo, acute d-amphetamine administration was associated with clinically meaningful improvement on measures of executive function and visual attention and vigilance, and with modest improvements on a measure of speed of processing. These results suggest that a brief computerized cognitive test battery designed for repeat administration, in combination with a statistical approach that emphasizes individual-level change, provides a sensitive approach to detecting the effect of cognitive-enhancing medications in people with chronic schizophrenia.