Adverse Effects of Risperidone on Eye Movement Activity: A Comparison of Risperidone and Haloperidol in Antipsychotic-Naive Schizophrenic Patients

Sweeney, John A.

doi:10.1016/s0893-133x(96)00195-9

Cited by 45 publications

(18 citation statements)

References 70 publications

(61 reference statements)

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“…The observation of such an impairment, which is consistent with animal models of the effects of dopamine receptor blockade (Wang et al, 2004) and observations in PD (Hodgson et al, 1999), stands out by way of comparison with the pattern of generalized enhancement on neuropsychological tests reported in clinical trials with risperidone and other antipsychotic treatments (Harvey et al, 2005;Keefe et al, 2006;Woodward et al, 2005). Findings from the present study, and others Sweeney et al, 1997), suggest that translational oculomotor biomarkers may provide sensitive and specific tools for drug discovery and evaluation by parsing drug effects on discrete neurocognitive operations.…”

Section: Resultssupporting

confidence: 87%

Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Harris

Wiseman

Reilly

et al. 2008

Neuropsychopharmacol

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Studies of procedural learning in medicated schizophrenia patients using predictive saccade paradigms have consistently demonstrated hypometric predictive responses. Findings from antipsychotic-naive schizophrenia patients indicate fewer or no deficits. This pattern of findings suggests that antipsychotic medications might adversely affect frontostriatal systems supporting procedural learning on this task. The accuracy and latency of predictive saccades were assessed in 25 antipsychotic-naive first-episode schizophrenia patients and 22 matched healthy individuals. Patients were retested after 6 weeks of treatment with risperidone. Healthy individuals were reevaluated after a similar time period. The ability to learn to time response initiation in anticipation of target appearance (target prediction) was not impaired in patients before or after treatment. In contrast, although no deficits were evident before treatment initiation, after treatment patients showed a marked decrease in the accuracy of predictive but not sensory-guided responses. The findings from pretreatment testing indicate that procedural learning is a relatively unaffected cognitive domain in antipsychotic-naive first-episode schizophrenia. Although treatment-emergent extrapyramidal symptoms were minimal, these data suggest that D2 antagonism in striatum after risperidone treatment was sufficiently robust to disrupt the generation of planned volitional behavior guided by internalized representations.

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Section: Resultssupporting

confidence: 87%

Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Harris

Wiseman

Reilly

et al. 2008

Neuropsychopharmacol

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“…Risperidone treatment was associated with decreased peak velocity and a modest decrease in prosaccade gain (Reilly et al, 2005) and reduction in antisaccade latency (Harris et al, 2006). These effects observed with risperidone were not observed with haloperidol (Harris et al, 2006; Sweeney et al, 1997). In another study of antipsychotic-naïve patients performing a memory guided saccade task with a variable delay period duration, schizophrenia patients prior to treatment demonstrated a delay dependent impairment with reduced gain of saccade to remembered locations at only the longest delay period duration compared to controls (Reilly, Harris, Keshavan, & Sweeney, 2006).…”

Section: Investigations Of Pharmacologic Effects On Eye Movements mentioning

confidence: 79%

Pharmacological treatment effects on eye movement control

Reilly

Lencer

Bishop

et al. 2008

Brain and Cognition

205

142

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The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second-generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson's disease, and Huntington's disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.

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“…Investigations of saccadic eye movements indicate that oculomotor responses may be more affected by second-generation than first-generation antipsychotics, 39–42 but the effects on pursuit have not been systematically studied. Some evidence indicates that clozapine impairs pursuit, but studies included only small sample sizes and examined only pursuit maintenance.…”

mentioning

confidence: 99%

Effects of Second-Generation Antipsychotic Medication on Smooth Pursuit Performance in Antipsychotic-Naive Schizophrenia

Lencer

Sprenger²,

Harris

et al. 2008

Arch Gen Psychiatry

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Context Analyses of smooth pursuit eye movement parameters in patients with schizophrenia provide information about the integrity of neural networks mediating motion perception, sensorimotor transformation, and cognitive processes such as prediction. Although pursuit eye tracking deficits have been widely reported in schizophrenia, the integrity of discrete components of pursuit responses and the effect of second-generation antipsychotic medication on them are not well established. Objective To examine different components of smooth pursuit performance in antipsychotic-naive patients with schizophrenia before and after treatment with second-generation antipsychotic medication. Design, Setting, and Participants Thirty-three antipsychotic-naive patients with schizophrenia performed 3 different smooth pursuit paradigms designed to evaluate specific components of the pursuit response. All of the patients were retested after 6 weeks of treatment with risperidone or olanzapine. Testing was also performed with 39 matched healthy individuals. Thirteen patients and 21 healthy participants were retested after 26 and 52 weeks. Main Outcome Measures Pursuit initiation, maintenance gain (ratio of eye velocity over target velocity), and frequency of catch-up saccades during pursuit maintenance. Results Prior to treatment, pursuit gain when tracking less predictable ramp targets tended to be reduced, latency of pursuit initiation was speeded, and catch-up saccade frequency was increased during predictive pursuit. After antipsychotic treatment initiation, pursuit gain decreased with ramp targets, indicating treatment-emergent impairments in sensorimotor processing. No changes were observed for predictive pursuit. Exploratory analyses in the subgroup with follow-up to 1 year revealed that these effects continued through long-term follow-up with some partial normalization at 1 year. Deficits were unrelated to drug dosage and clinical ratings. Conclusions Impaired sensorimotor function was observed after initiation of second-generation antipsychotic medications, which may be explained by their serotonergic antagonism of brainstem sensorimotor systems. Predictive mechanisms supported by frontostriatal-cerebellar circuitry were not affected by treatment initiation and appear able to compensate for treatment-emergent sensorimotor impairments during predictive tracking.

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Adverse Effects of Risperidone on Eye Movement Activity: A Comparison of Risperidone and Haloperidol in Antipsychotic-Naive Schizophrenic Patients

Cited by 45 publications

References 70 publications

Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Effects of Risperidone on Procedural Learning in Antipsychotic-Naive First-Episode Schizophrenia

Pharmacological treatment effects on eye movement control

Effects of Second-Generation Antipsychotic Medication on Smooth Pursuit Performance in Antipsychotic-Naive Schizophrenia

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