A randomised, double-blind, placebo-controlled trial of tropisetron in patients with schizophrenia.

Akihiro Shiina,Nobuhisa Kanahara,Goro Fukami,Taisuke Yoshida,Tasuku Hashimoto,Michiko Nakazato,Yukihiko Shirayama,Tadashi Hasegawa,Kenji Hashimoto,Masaomi Iyo,Tetsuya Shiraishi,Tomihisa Niitsu,Tadashi Haraguchi,Mihisa Fujisaki

doi:10.1186/1744-859x-9-27

Abstract

BackgroundCognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Auditory sensory gating P50 deficits are correlated with neuropsychological deficits in attention, one of the principal cognitive disturbances in schizophrenia. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR) agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. Therefore, it is of particular interest to investigate the effects of tropisetron on the cognitive deficits in patients with schizophrenia.MethodsA randomised, placebo-controlled trial of tropisetron in patients with schizophrenia was performed. A total of 40 patients with chronic schizophrenia who had taken risperidone (2 to 6 mg/day) were enrolled. Subjects were randomly assigned to a fixed titration of tropisetron (n = 20, 10 mg/day) or placebo (n = 20) in an 8-week double-blind trial. Auditory sensory gating P50 deficits and Quality of Life Scale (QLS), Cambridge Neuropsychological Test Automated Battery (CANTAB), and Positive and Negative Syndrome Scale (PANSS) scores were measured.ResultsIn all, 33 patients completed the trial. Tropisetron was well tolerated. Administration of tropisetron, but not placebo, significantly improved auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The score on the rapid visual information processing (sustained visual attention) task of CANTAB was significantly improved by tropisetron treatment. Total and subscale scores of PANSS were not changed by this trial. QLS scores in the all patients, but not non-smoking patients, were significantly improved by tropisetron trial.ConclusionsThis first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.

Highlights

Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease
Several lines of evidence suggest that the α7 subtype of the nicotinic acetylcholine receptors (α7 nAChRs) plays an important role in the mechanism of auditory P50 gating deficits of schizophrenia, and that α7 nAChR agonists are potential therapeutic drugs for the deficient inhibitory processing of the P50 auditory evoked potential that contributes to the cognitive deficits in schizophrenia [717]
We previously reported that tropisetron normalises deficient auditory gating in DBA/2 mice and that this effect of tropisetron was blocked by coadministration of the selective α7 nAChR antagonist methyllycaconitine (MLA) [20]

Summary

Introduction

Cognitive deficits in schizophrenia are associated with psychosocial deficits that are primarily responsible for the poor long-term outcome of this disease. Our studies suggest that the α7 nicotinic acetylcholine receptor (α7 nAChR) agonist tropisetron might be a potential therapeutic drug for cognitive deficits in schizophrenia. The neuropharmacological and neurobiological effects of tropisetron demonstrated by our group suggest the need for future studies to assess the effects of tropisetron on cognitive dysfunction in schizophrenia, because P50 deficits have been previously associated with attentional deficits in schizophrenia [24]. These attentional deficits are in turn associated with psychosocial deficits that are primarily responsible the poor long-term outcome of schizophrenia [1]

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Conclusion