title: 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 > or = 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 < or = 0.04). No ketamine by risperidone interactions were found (all P > or = 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.
authors: Department of Neuroimaging, Institute of Psychiatry, King's College London, London, UK.
authors: A
authors: A
authors: Schmechtig
authors: J
authors: J
authors: Lees
authors: A
authors: A
authors: Perkins
authors: A
authors: A
authors: Altavilla
authors: K J
authors: KJ
authors: Craig
authors: G R
authors: GR
authors: Dawson
authors: J F
authors: JF
authors: William Deakin
authors: C T
authors: CT
authors: Dourish
authors: L H
authors: LH
authors: Evans
authors: I
authors: I
authors: Koychev
authors: K
authors: K
authors: Weaver
authors: R
authors: R
authors: Smallman
authors: J
authors: J
authors: Walters
authors: L S
authors: LS
authors: Wilkinson
authors: R
authors: R
authors: Morris
authors: S C R
authors: SC
authors: Williams
authors: U
authors: U
authors: Ettinger
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects* / Q000494:pharmacology; D053483:Eye Movement Measurements; D005133:Eye Movements / Q000187:drug effects; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007649:Ketamine / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D015835:Ocular Motility Disorders / Q000139:chemically induced / Q000188:drug therapy*; D011698:Pursuit, Smooth / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012438:Saccades / Q000187:drug effects; D012559:Schizophrenia; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D018967:Risperidone