fMRI studies reveal the involvement of the dorsolateral prefrontal cortex and the Buparlisib cell line anterior cingulate cortex in the modafinil-induced improvement of cognitive deficits in schizophrenia. All studies discussed in this review had small sample sizes, which makes them vulnerable for type II errors. Possibly

due to the small sample sizes the positive outcomes did not reach the level of statistical significance. Positive effects of modafinil on cognition and fatigue are best demonstrated in patients with poor pre-existing functioning. Evidence for this hypothesis is provided by research in both animal and human studies [Hunter et Inhibitors,research,lifescience,medical al. 2006; McFadden et al. 2010]. Since most studies did not exclude

relatively good functioning patients, the effect of modafinil might be underestimated Inhibitors,research,lifescience,medical (ceiling effect). Whether this could also account for armodafinil is unclear. The antipsychotic drugs used in the reviewed studies differed, even within the study populations. Modafinil and armodafinil might exert different effects when added to typical or atypical antipsychotic drugs. Modafinil may particularly improve cognitive functioning in patients using typical antipsychotic drugs [Spence et al. 2005], while effects of modafinil on activity and fatigue might be stronger in patients using atypical Inhibitors,research,lifescience,medical antipsychotic drugs, since atypical drugs have more sedative side effects. Effect measurements differed between the accounted studies, which makes a comparison difficult and for some studies even Inhibitors,research,lifescience,medical impossible. Some studies use subjective measurements, others a small subset of cognitive tests, that do not cover all cognitive deficits in schizophrenia. To be able to fully assess the usefulness Inhibitors,research,lifescience,medical of modafinil and armodafinil as add-on therapy in schizophrenia, measurement

instruments used to assess cognitive function have to be more uniform. Modafinil and armodafinil dosage and duration of treatment and follow up differ widely. The defined daily dosage of modafinil for narcolepsy is 300 mg/day. It could be that a lower dosage causes only small effect sizes or is ineffective. Whether modafinil and armodafinil can establish weight loss in patients with antipsychotic-induced overweight is unclear. If so, weight reduction may be caused by an increase in activity or by an unknown other mechanism. When modafinil and armodafinil produce weight Phosphoprotein phosphatase loss, it would therefore be interesting to investigate whether or not weight reduction is more pronounced in inactive patients who become more active with modafinil and armodafinil than in active patients with no activity increase in response to the substance. The risk of worsening of psychotic symptoms and, in the case of clozapine use, a rise of clozapine serum levels must be taken into account when the addition of modafinil is considered.