Amphetamine-related improvement in executive function in patients with chronic schizophrenia is modulated by practice effects

BackgroundAmelioration of cognitive impairment is an important treatment goal for a broad range of neuropsychiatric disorders, including schizophrenia. One critical issue in clinical trial design is the extent to which repeated exposure to cognitive tests (i.e., practice effects) may lead to improvement in performance on the cognitive tests in the absence of any true treatment effect. The current study examined the extent to which practice effects on a measure of executive function may influence the sensitivity of that task to detecting the cognitive-enhancing effects of a single acute dose of d-amphetamine in individuals with chronic schizophrenia.MethodsTwenty-four men with chronic schizophrenia were randomized to receive a constant or random/matched alternate form version of a hidden maze learning measure of executive function (Groton Maze Learning Test; GMLT) on four separate occasions in one month. They also completed a measure of psychomotor speed. Using a double-blind, placebo-controlled, parallel groups design, cognitive function following administration of a single dose of d-amphetamine (20 mg p.o) or placebo was then assessed.ResultsThe group who received the constant-pathway version of the GMLT showed a large practice effect (d = 2.05) over four practice sessions. Consequently, they did not evidence any improvement on the GMLT following d-amphetamine administration. In contrast, the group who received the random/matched alternate version of the GMLT showed a statistically significant and large effect size (d = .84) improvement on this measure. Both groups showed d-amphetamine-related improvement on a measure of psychomotor speed.ConclusionsResults of this study suggest that practice effects associated with repeated exposure to a cognitive test could obscure the sensitivity of the test to detecting true treatment-related cognitive improvement.