Abstract
Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.
Highlights
Serotonin (5-HT) is a biogenic monoamine with a complex role in regulation of the sleep-wake cycle, appetite, pain, body temperature, vomiting, cognitive, perceptual and affective functions [1]
A priori comparison made for T/C ratio after 2 h using two-tailed Student’s t test
Figural Memory: Participant required to identify the correct figure Other Subtests performed by Akhonzadeh: Verbal Paired Associates: Recall accuracy of words paired with other words Logical Memory: Ability to recall narrative features of a section of prose Digit Span: Ability to recall span of digits presented sequentially
Summary
Serotonin (5-HT) is a biogenic monoamine with a complex role in regulation of the sleep-wake cycle, appetite, pain, body temperature, vomiting, cognitive, perceptual and affective functions [1]. Received: 16 June 2021 Revised: 9 December 2021 Accepted: 16 December 2021 cognitive effects of 5HT3 receptor antagonist ondansetron in palonosetron, tropisetron, dolasetron, granisetron) and compared to those not animal models that are relevant for psychosis in humans [12]: Ondansetron attenuated amphetamine-induced dopamine release in mesocorticolimbic regions without inducing parkinsonism [9, 10, 13]; and reversed impairments in sensory gating and visual processing in the DBA/2 mouse model of α7-nicotinic cholinergic receptor depletion, by increasing hippocampal acetylcholine release [14, 15]. Efficacy in the treatment of both negative and cognitive symptoms, including some evidence of improved visual information processing [21,22,23], and the drug is under phase II evaluation in a Trial of Ondansetron as a Parkinson’s HAllucinations treatment (TOP HAT) (Clinical trials.gov NCT04167813).
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