Predictors and mediators of add-on mirtazapine-induced cognitive enhancement in schizophrenia--a path model investigation.

We aimed to evaluate predictors and mediators of enhancing effect of adjunctive mirtazapine on cognition in schizophrenia. Patients with difficult-to-treat schizophrenia received either mirtazapine (n = 19) or placebo (n = 18) in a double-blind fashion for six weeks. Mirtazapine outperformed placebo on the Block Design and Stroop Dots. In the present subsidiary study, factors underlying this difference were explored with Path Analysis. Add-on mirtazapine had an independent enhancing effect on the Block Design-measured visuo-spatial functioning. Further, this effect was mediated via changes in positive, depressive and parkinsonism symptoms, but not in negative symptoms. This effect was predicted by higher doses of FGAs, longer duration of illness and lower initial Block Design scores. Path Analysis model fit was good. Mirtazapine may have direct and indirect favorable effects on visuo-spatial functioning, but further research is needed. Path analysis may be a feasible statistical method for further research of neurocognition in psychopharmacological interventions in schizophrenia. This article is part of a Special Issue entitled 'Cognitive Enhancers'.