Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome.

Fourteen patients (7 male, 7 female, 22-63 years), classified as having chronic fatigue syndrome (CFS), but without concurrent major depression, significant sleepiness or use of psychoactive medication, completed a double-blind, placebo-controlled, crossover study of the effects of the selective wakefulness-promoting agent, modafinil (200 and 400mg/day). The treatment periods were each 20 days, with washout periods of 2 weeks. The primary aim was to determine effects on cognition and the secondary aim was to determine effects on self-ratings of fatigue, quality of life and mood. Modafinil had mixed effects in two cognitive tasks. In a test of sustained attention, treatment with 200mg reduced the latency to correctly detect sequences, but 400mg increased the number of missed targets. In a test of spatial planning, the 200mg dose resulted in a slower initial thinking time for the easiest part of the task, whereas 400mg reduced the initial thinking time for the hardest part of the test. Lastly, in a test of mental flexibility and one of motor speed, patients performed worse whilst on modafinil (400mg), compared with the placebo period. No effects were observed on the performance of other psychometric tests or on self-ratings of fatigue, quality of life or mood, but this may have been due to insufficient statistical power. It is discussed whether the limited and mixed cognitive effects that we observed could have occurred by chance, or whether a subgroup of CFS patients with daytime sleepiness would have shown greater benefits.

Cognitive effects of modafinil in student volunteers may depend on IQ.

The results of two previous studies on the effects of modafinil, a selective wakefulness-promoting agent, in healthy university students were combined in a retrospective analysis. This allowed determination of whether the effects of modafinil were dependent on IQ and whether the larger sample size (n=89) would reveal more cognitive benefits. A battery of cognitive tests was completed 2-3 h after dosing. In the whole sample, modafinil (200 mg) significantly reduced the number of missed targets in a test of sustained attention (RVIP). However, interestingly, several interactions between modafinil and IQ emerged. Modafinil (100 and 200 mg) significantly improved target sensitivity in the RVIP test, but only in the group of 'lower' IQ (mean+/-sem=106+/-0.6), not in the 'higher' IQ group (mean+/-sem=115.5+/-0.5). Furthermore, there were significant modafinil x IQ interactions in two further tests. Modafinil significantly reduced speed of responding in a colour naming of dots, and in clock drawing, but only in the 'lower' IQ group. Thus, the cognitive benefits of modafinil seem particularly marked in tests of vigilance and speed, in which sleepiness would be an important factor. Furthermore, the results indicate that high IQ may limit detection of modafinil's positive effects.

Does modafinil enhance cognitive performance in young volunteers who are not sleep-deprived?

In a double-blind, parallel groups study, 60 healthy student volunteers (29 men and 31 women, aged 19-22 years) were randomly allocated to receive placebo, 100 or 200 mg modafinil. Two hours later, in the early evening, they completed an extensive cognitive battery. The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session, and there were no treatment-associated changes in these or in mood ratings during the tests. Modafinil was without effect in several tests of reaction time and attention, but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention. Modafinil was without effect on spatial working memory, but the 100-mg group performed better in the backward part of the digit span test. Modafinil was without effect on verbal short-term memory (story recall), but 100 mg improved digit span forward, and both doses improved pattern recognition, although this was accompanied by a slowing of response latency in the 200-mg group. There were no significant effects of modafinil compared with placebo in tests of long-term memory, executive function, visuospatial and constructional ability, or category fluency. These results suggest that the benefits of modafinil are not clearly dose-related, and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory, which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals.

Does drinking have effects on mood and cognition in male and female students?

Self-ratings of mood and bodily symptoms were made by groups of IQ and education-matched male and female students [teetotal, low (2-9 units/week for both sexes; 1 UK unit=8 g alcohol) and moderate (12-34 units/week for males; 10-24 units/week for females) drinkers], before the start and at the end of cognitive testing. Multivariate analyses of variance (MANOVAs) showed that there were significant Alcohol x Time interactions, because the teetotal group responded to the cognitive tests with greater increases in the factors of somatic anxiety and aggressive mood than did the other two groups. Thus, the teetotallers had greater ratings of anxiety, sweating, palpitations, irritability, headache, feeling angry, quarrelsome, belligerent, resentful, hostile, spiteful and rebellious. No differences were found in immediate or delayed logical memory, in verbal fluency, trails, clock-drawing or mental flexibility tests. In tests of sustained attention [rapid visual information processing (RVIP)] and planning, males performed better than females. The moderate-alcohol group performed better than the low-alcohol group in RVIP and planning (completed significantly more tasks in the minimum moves), although in the hardest parts of the latter test, they took longer in planning the initial move. In conclusion, there was no evidence that the group drinking moderate levels of alcohol had any cognitive impairment and the teetotal group responded to the cognitive tests with the greatest increases in negative mood.

The cognitive-enhancing properties of modafinil are limited in non-sleep-deprived middle-aged volunteers.

Modafinil is a selective wakefulness-promoting agent that has been shown to enhance cognitive performance under conditions of sleep deprivation but which has equivocal effects in normal young volunteers. In a double-blind parallel group design study, 45 non-sleep-deprived middle-aged volunteers (20 men and 25 women, aged 50-67 years) were randomly allocated to receive two capsules containing placebo, 100 or 200 mg modafinil, and 3 h later they completed 100 mm visual analogue scales of mood and bodily symptoms, before and after an extensive battery of cognitive tests [pen and paper and the Cambridge Neuropsychological Test Automated Battery (CANTAB)]. There were no significant treatment-associated changes in ratings of mood or bodily symptoms and no significant effects on most of the cognitive tests used in this study. The group treated with modafinil (200 mg) was significantly faster in a simple colour naming of dots and also significantly better in a test of constructional ability (Clock Drawing Test) compared with the placebo group. However, subjects in the 200-mg group also made significantly more total errors in the Intra/Extradimensional Set Shift (ID/ED) task than both the other groups. Thus, this study found limited evidence of cognitive-enhancing properties of modafinil in healthy middle-aged volunteers.

Modafinil affects mood, but not cognitive function, in healthy young volunteers.

Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation. In a double-blind study we examined its effects in 30 healthy, non sleep-deprived students (19 men and 11 women, aged 19-23 years), who were randomly allocated to placebo, 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms, before and after an extensive battery of cognitive tests (pen and paper and CANTAB). There were no significant differences between the three treatment groups on any of the cognitive tests used in this study. There was a significant post-treatment change in the factor measuring 'somatic anxiety' and in individual ratings of 'shaking', 'palpitations', 'dizziness', 'restlessness', 'muscular tension', 'physical tiredness' and 'irritability', which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups. Further changes in mood were revealed after the stress of cognitive testing, with the 100 mg group showing greater increases in the 'psychological anxiety' and the 'aggressive mood' factors (as measured from the Bond and Lader scales).