Schizophrenia is associated with persistent cognitive deficits, which worsen treatment outcomes despite increasing antipsychotic doses. This study aimed to assess the effect of levetiracetam on the severity of schizophrenia symptoms and cognitive deficits in these patients.

In this randomized, controlled, three-blind randomized clinical trial approved by Mashhad University of Medical Sciences, Iran (IRCT20101130005280N31), forty chronic schizophrenic patients aged 18–60 years were randomly divided into two groups of levetiracetam and placebo. The levetiracetam group received levetiracetam for 8 weeks. The symptoms were evaluated by Positive and Negative Symptoms Scale (PANSS), Stroop test, Digit Span test and Wisconsin Test at baseline, 4th week, and 8th week. Data were analyzed through SPSS V. 23 software, descriptive tests and inferential statistics.

At the end of the study, all subscales of the PANSS questionnaire reduced significantly (P < 0.05). Also, all subscales of the cognitive tests had significant changes. The trends of digit span tests, correct number of consonants and inconsonant were increasing. While the trends related to consonant errors, inconsistent errors, consistent reaction time and nonconsistent reaction time were decreasing. The changes in the number of classes were increased while changes in preservation error were decreased.

The results showed that levetiracetam has significant effects on clinical symptoms, especially negative symptoms. Also, it impacts significantly on cognitive functions. It is recommended that it be added to the pharmacological regimen of these patients to improve their clinical symptoms, quality of life and treatment outcomes.