The effects of ketamine and risperidone on eye movement control in healthy volunteers

Abstract

The non-competitive N-methyl-D-aspartate 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 (PS) and antisaccades (AS) while being randomly assigned to one of four drug groups (intravenous 100 ng ml−1 ketamine, 2 mg oral risperidone, 100 ng ml−1 ketamine plus 2 mg 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 PS or AS (all P⩾0.07). An effect of risperidone was observed for amplitude gain and peak velocity of PS and AS, indicating hypometric gain and slower velocities compared with 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 optimise pharmacological treatment of schizophrenia.

An Overview of the Association between Schizotypy and Dopamine

“…Such studies tend to take place in well-controlled laboratory settings using tight methodological controls, such as double-blind procedures and placebo conditions [e.g., Ref. ( 59 – 61 )]. Such paradigms inform on acute drug effects and their interaction with schizotypy.…”

Ketamine-induced brain activation in awake female nonhuman primates: a translational functional imaging model

“…Thus, phMRI provides a reliable, in vivo imaging methodology for studying the whole-brain pharmacological effects of ketamine. Of particular relevance to schizophrenia, pretreatment with the antipsychotic risperidone has been shown to attenuate the subjective effects (Schmechtig et al 2013), BOLD activation (Doyle et al 2013), and functional changes (Joules et al 2015) induced by ketamine. This is particularly interesting because while risperidone acts as an antagonist with high affinity for dopamine D2, 5-HT2a, and a number of other receptors (Meltzer and McGurk 1999), like other clinical antipsychotic compounds it does not interact directly with NMDARs.…”

Precompetitive Consortium Approach to Validation of the Next Generation of Biomarkers in Schizophrenia

“…Validation of the next generation of biomarkers in schizophrenia Editorial influence the antisaccade error rate, latencies or saccadic amplitude gain, which are reported to be impaired in schizophrenia [16], and risperidone had no effects on the ketamine-induced deficits in smooth-pursuit eye movements [15]. The limited effect of ketamine on cognitive biomarkers was surprising and it could be argued that the dose used was too low to show significant effects.…”

“…An exception was the eye movement task, in which ketamine caused some occulomotor performance deficits similar to those seen in schizophrenia. Thus, ketamine increased saccadic frequency and decreased velocity gain of smooth-pursuit eye movements [15]. However, ketamine did not future science group www.futuremedicine.com…”