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Modafinil and cognitive enhancement in schizophrenia and healthy volunteers: the effects of test battery in a randomised controlled trial

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J. Lees, P. G. Michalopoulou, S. W. Lewis, S. Preston, C. Bamford, T. Collier, A. Kalpakidou, T. Wykes, R. Emsley, G. Pandina, S. Kapur, R. J. Drake

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalPsychological Medicine
Early online date3 May 2017
Accepted/In press16 Mar 2017
E-pub ahead of print3 May 2017


  • Modafinil and cognitive enhancement_LEES_Publishedonline3May2017_GREEN AAM

    Modafinil_and_cognitive_enhancement_LEES_Publishedonline3May2017_GREEN_AAM.pdf, 621 KB, application/pdf

    Uploaded date:13 Jul 2017

    Version:Accepted author manuscript

    This article has been published in a revised form in Psychological Medicine, at This version is free to view and download for private research and study only. Not for re-distribution, re-sale or use in derivative works. © Cambridge University Press 2017

King's Authors


Background: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. Methods: A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years’ duration of DSM-IV schizophrenia, on stable antipsychotic medication. In parallel, the same design was used in 28 age-, sex-, and education-matched healthy volunteers. Uncorrected p values were calculated using mixed effects models. Results: In patients, modafinil significantly improved CANTAB Paired Associate Learning, non-significantly improved efficiency and significantly slowed performance of the CANTAB Stockings of Cambridge spatial planning task. There was no significant effect on any MCCB domain. In healthy volunteers, modafinil significantly increased CANTAB Rapid Visual Processing, Intra-Extra Dimensional Set Shifting and verbal recall accuracy, and MCCB social cognition performance. The only significant differences between groups were in MCCB visual learning. Conclusions: As in earlier chronic schizophrenia studies, modafinil failed to produce changes in cognition in early psychosis as measured by MCCB. CANTAB proved more sensitive to the effects of modafinil in participants with early schizophrenia and in healthy volunteers. This confirms the importance of selecting the appropriate test battery in treatment studies of cognition in schizophrenia.

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