The Effects of Ketamine and Risperidone on Eye Movement Control in Healthy Volunteers

Anne Schmechtig, Jane Lees, Adam Perkins, Anna Altavilla, Kevin J. Craig, Gerard R. Dawson, John Francis William Deakin, Colin T. Dourish, Lisa H Evans, Ivan Koychev, Kristin Weaver, Richard Smallman, James Walter, Lawrence S Wilkinson, Robin Morris, Steven C R Williams, Ulrich Ettinger

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17 Citations (Scopus)


The non-competitive NMDA receptor antagonist ketamine leads to transient psychosis-like symptoms and impairments in oculomotor performance in healthy volunteers. This study examined whether the adverse effects of ketamine on oculomotor performance can be reversed by the atypical antipsychotic risperidone.
In this randomized double-blind, placebo-controlled study 72 healthy participants performed smooth pursuit eye movements (SPEM), prosaccades and antisaccades while being randomly assigned to one of four drug groups (intravenous 100 ng/ml ketamine, 2mg oral risperidone, 100 ng/ml ketamine plus 2mg oral risperidone, placebo).
Drug administration did not lead to harmful adverse events. Ketamine increased saccadic frequency and decreased velocity gain of SPEM (all p<0.01) but had no significant effects on prosaccades or antisaccades (all p≥0.07). An effect of risperidone was observed for amplitude gain and peak velocity of prosaccades and antisaccades, indicating hypometric gain and slower velocities compared to placebo (both p≤0.04). No ketamine by risperidone interactions were found (all p≥0.26).
The results confirm that the administration of ketamine produces oculomotor performance deficits similar in part to those seen in schizophrenia. The atypical antipsychotic risperidone did not reverse ketamine induced deteriorations. These findings do not support the cognitive enhancing potential of risperidone on oculomotor biomarkers in this model system of schizophrenia and point towards the importance of developing alternative performance-enhancing compounds to optimize pharmacological treatment of schizophrenia.
Original languageEnglish
Article numbere334
Pages (from-to)N/A
Number of pages10
JournalTranslational psychiatry
Issue numberN/A
Publication statusE-pub ahead of print - 2013


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  • Acknowledged-BRC-13/14


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