Several questions remain unanswered regarding the magnitude and time course of cognitive improvement in response to antipsychotic treatment. The purpose of this study was to assess changes in cognitive performance in antipsychotic-naive or minimally medicated patients with first-episode schizophrenia during the first 12 months of treatment, in a case–control design. Patients were treated with flupenthixol decanoate depot injection, according to a standard algorithm. The primary outcome measure was change in MATRICS Cognitive Consensus Battery (MCCB) composite score over 12 months.

The sample comprised 92 patients and 100 healthy controls matched for age, sex, ethnicity and educational status. Cognitive function was assessed by means of the MCCB.

A mixed-effects model identified a significant group × time effect (p ≤ 0.0001) for the MCCB composite score, with patients showing a greater degree of change than the controls. For the other MCCB domains there were significant group × time effects at adjusted significance level for attention and vigilance (p ≤ 0.0001), visual learning (p ≤ 0.0001), verbal learning (p = 0.005) and working memory (p ≤ 0.0001), but not for reasoning and problem solving (p = 0.04), speed of processing (p = 0.03) and social cognition (p = 0.06). There were moderate correlations between change in MCCB composite score and change in symptomatology as assessed by Positive and Negative Syndrome Scale factor analysis-derived domains.

Substantial improvements in cognitive function were observed over and above a practice effect, and were significantly correlated with improvements in psychopathology and functionality.