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. 2010 Jun 24:9:27.
doi: 10.1186/1744-859X-9-27.

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

Akihiro Shiina  1 , Yukihiko Shirayama, Tomihisa Niitsu, Tasuku Hashimoto, Taisuke Yoshida, Tadashi Hasegawa, Tadashi Haraguchi, Nobuhisa Kanahara, Tetsuya Shiraishi, Mihisa Fujisaki, Goro Fukami, Michiko Nakazato, Masaomi Iyo, Kenji Hashimoto
Affiliations

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

Akihiro Shiina et al. Ann Gen Psychiatry. .

Abstract

Background: Cognitive 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 alpha7 nicotinic acetylcholine receptor (alpha7 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.

Methods: A 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.

Results: In 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.

Conclusions: This first randomised, double-blind, placebo-controlled trial supports the safety and efficacy of adjunctive tropisetron for treatment of cognitive deficits in schizophrenia.

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Figures

Figure 1
Figure 1
Effect of tropisetron on auditory sensory gating P50 deficits in non-smoking patients with schizophrenia. The ratio of test P50 amplitude to conditioning amplitude was measured at baseline and 8 weeks after placebo or tropisetron treatment. Tropisetron (t = 2.70, degrees of freedom (df) = 11, P = 0.021), but not placebo (t = 1.66, df = 9, P = 0.132), significantly decreased the P50 ratio in non-smoking patients with schizophrenia. Data are from the placebo group (n = 10) and the tropisetron group (n = 12).
Figure 2
Figure 2
Rapid visual information processing (RVP) scores on Cambridge Neuropsychological Test Automated Battery (CANTAB) subtests for non-smoking patients with schizophrenia during treatment placebo and tropisetron. There were significantly different scores for RVP (t = -5.78, degrees of freedom (df) = 11, P < 0.001) in the tropisetron group, but not the placebo group. Data are from the placebo group (n = 12) and the tropisetron group (n = 12).
See this image and copyright information in PMC

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