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

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
  • Psychological Medicine, May 2017, Cambridge University Press
  • DOI: 10.1017/s0033291717000885

What is it about?

Schizophrenia worsens cognitive skills like attention, memory and planning and trials of treatments for these problems require "batteries" of tests to measure the impairments. Such batteries must be reliable and sensitive to the changes caused by treatment. We compared two commonly used batteries (MCCB & CANTAB) before and after the cognition enhancing drug modafinil in 46 people who had recently developed schizophrenia and 28 healthy volunteers. We hypothesised that modafinil would have similar effects in both groups, that this would return some of schizophrenia's impairments towards normal and that both batteries would identify the same changes. The MCCB detected no changes in the schizophrenia group, while the CANTAB identified improved visual learning and significantly slower but slightly better performance on a planning task. The MCCB also found that healthy volunteers improved on a test of understanding social situations - the CANTAB version we used lacked such a task. The CANTAB found that healthy volunteers improved on flexibility of thinking and visual processing. When we compared the effect of modafinil in the healthy and unwell groups, the only difference the MCCB identified was that modafinil in healthy volunteers improved visual learning signficantly more and the CANTAB identified no differences. Limitations to the study included testing small numbers of healthy volunteers, using only single doses of modafinil rather than a longer course, and the need to compare performance on many tests increasing the risk of picking out chance differences in performance as "significant". We concluded that there was little evidence that modafinil had very different effects in the two groups, that fewer improvements occurred in those with schizophrenia than in some other studies but those that did occur were similar to past findings, and that there were differences between the two batteries. The CANTAB, although it alone detected changes in healthy visual processing did not confirm the MCCB's finding of greater benefit of modafinil for visual memory in health than illness. Overall, some of its tasks appeared more sensitive to changes in schizophrenia sufferers than the MCCB scores we analysed. We concluded that there was evidence of differences between cognitive test batteries that other experimenters should consider when planning similar experiments.

Why is it important?

Cognitive test batteries are essential elements in any trial of a cognition enhancing drug and researchers are very interested in developing drugs or other treatments to improve cognition in those with schizophrenia. Such impairments are responsible for much of the (often profound) disability caused by the disorder, which will afflict nearly 1% of the population at some stage. Modafinil has some evidence that it is beneficial, but the results are not consistent. Using the same cognitive tests in different studies makes the results comparable, but this makes finding the best battery for such studies all the more important. Our finding that there was some evidence of differences fits a previous study of ours in those with long standing schizophrenia, which found that the MCCB and another test battery were less similar than we expected, except when it came to global (overall) scores. It appears that there is further work to be done in this area.

Perspectives

Richard Drake
University of Manchester

Studies like this are unglamorous but important in establishing the rigour of more eye-catching work, for instance trials of new treatments for psychosis. As a clinician I work to rehabilitate people with schizophrenia and we are desperate for treatments for cognitive impairment because it can make normal social activity so difficult. Our team had expected more evidence of benefit from modafinil, given previous work in those who had only recently become ill: though it was reassuring to detect some changes which fitted previous findings. Our most important finding was that there appeared to be differences between batteries, as we discovered in previous work comparing the MCCB to another battery, CogState's SB. Despite all the work that goes into developing such batteries it seems we still cannot take the results of studies of cognition in schizophrenia for granted. We may need further work to develop or identify reliable tasks that we understand thoroughly and that are sensitive to the effects of treatment.

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http://dx.doi.org/10.1017/s0033291717000885

The following have contributed to this page: Richard Drake and Professor Dame Til Wykes