Modafinil combined with cognitive training: pharmacological augmentation of cognitive training in schizophrenia

Several efforts to develop pharmacological treatments with a beneficial effect on cognition in schizophrenia are underway, while cognitive remediation has shown modest effects on cognitive performance. Our goal was to test if pharmacological augmentation of cognitive training would result in enhancement of training-induced learning. We chose modafinil as the pharmacological augmenting agent, as it is known to have beneficial effects on learning and cognition. 49 participants with chronic schizophrenia were enroled in a double-blind, placebo-controlled study across two sites and were randomised to either modafinil (200mg/day) or placebo. All participants engaged in a cognitive training program for 10 consecutive weekdays. The primary outcome measure was the performance on the trained tasks and secondary outcome measures included MATRICS cognitive battery, proxy measures of everyday functioning and symptom measures. 84% of the participants completed all study visits. Both groups showed significant improvement in the performance of the trained tasks suggesting potential for further learning. Modafinil did not induce differential enhancement on the performance of the trained tasks or any differential enhancement of the neuropsychological and functional measures compared to placebo. Modafinil showed no significant effects on symptom severity. Our study demonstrated that combining pharmacological compounds with cognitive training is acceptable to patients and can be implemented in large double-blind randomised controlled trials. The lack of differential enhancement of training-induced learning raises questions, such as choice and optimal dose of drug, cognitive domains to be trained, type of cognitive training, intervention duration and chronicity of illness that require systematic investigation in future studies.