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www.medwave.cl 1 doi: 10.5867/medwave.2015.05.6166
Research article
Medwave 2015 Jun;15(5):e6166 doi: 10.5867/medwave.2015.05.6166
Effects of modafinil on attention performance, short-
term memory and executive function in university
students. A randomized trial
Authors: Alejandro Fernández[1], Franco Mascayano[2], Walter Lips[1], Andrés Painel[3], Jonathan
Norambuena[3], Eva Madrid[4,5]
Affiliation:
[1] Escuela de Psicología, Universidad de Valparaíso, Valparaíso, Chile
[2] Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile
[3] Escuela de Medicina, Universidad de Valparaíso, Valparaíso, Chile
[4] Iberoamerican Cochrane Centre, Barcelona, Spain
[5] Centro de Investigaciones Biomédicas, Escuela de Medicina, Universidad de Valparaíso,
Valparaíso, Chile
[6] Departamento de Salud Pública Escuela de Medicina Universidad de Valparaìso
E-mail: emadrida@hsph.harvard.edu
Citation: Fernández A, Mascayano F, Lips W, Painel A, Norambuena J, Madrid E. Effects of modafinil
on attention performance, short-term memory and executive function in university students. A
randomized trial. Medwave 2015 Jun;15(5):e6166 doi: 10.5867/medwave.2015.05.6166
Submission date: 31/3/2015
Acceptance date: 5/6/2015
Publication date: 23/6/2015
Origin: not requested
Type of review: reviewed by two external peer reviewers, double-blind
Abstract
BACKGROUND
Modafinil is a drug developed and used for the treatment of excessive lethargy. Even though very
effective for sleep disorders, it is still controversial whether modafinil can improve performance in high-
order cognitive processes such as memory and executive function.
METHODS
This randomized, double-blind, placebo-controlled, crossover trial was designed to evaluate the effect
of modafinil (compared to placebo) on the cognitive functions of healthy students. 160 volunteers were
recruited and allocated randomly to modafinil or placebo group, and were assessed using the Stroop
Test, BCET test and Digit span test.
RESULTS
We found a significant difference in favor of modafinil compared to placebo in the proportion of correct
answers of Stroop Test in congruent situation. A significant shorter latency of modafinil group in the
incongruent situation of Stroop test was also found. No differences were found in Digit Span, or BCET
tests.
CONCLUSIONS
The study demonstrated that modafinil does not enhance the global cognitive performance of healthy
non-sleep deprived students, except regarding non-demanding tasks. In particular, this drug does not
seem to have positive effects on mental processes that sustain studying tasks in the college population
under normal conditions. We expect these findings to demystify the use of this drug and help decision
making concerning pharmacological public policies.
www.medwave.cl 2 doi: 10.5867/medwave.2015.05.6166
Introduction
Modafinil (2-[(diphenylmethyl) sulfinyl] acetamide) is a
psychostimulant with wakefulness-promoting properties. It
was available for commercial use in France in the 1990s [1].
Modafinil has demonstrated particular effectiveness for
treating lethargy and sleep
disorders [2],[3],[4],[5],[6],[7].
Some authors state that modafinil increases performance
of tasks associated with cognitive functions such as working
memory, visuospatial attention, and executive
function [8],[9],[10],[11],[12],[13],[14]. For others,
modafinil improves cognitive performance in healthy sleep
deprived adults, but only in regard to attentional function
and alertness [8],[9].
The primary mechanism of action is
unknown, [15] although its effects on different
neurotransmitter systems have been
demonstrated [1],[16],[17],[18],[19],[20],[21].
The use of stimulants to improve academic performance
has increased among the young population in the U.S. [22].
More than seven million Americans use over-the-counter
stimulants, and approximately 1.6 million of these people
are students [23],[24]. An online survey of more than
1,400 people from sixty countries showed that twenty
percent of respondents had used a psychoactive drug to
enhance their concentration or memory, and forty-four
percent of them had used modafinil. The population most
often associated with stimulant use to enhance attention
and memory are students between eighteen and twenty-
five years [25].
No formal studies have been reported on the use of
modafinil among students in Chile. However, some media
surveys reported an increase in the consumption of
stimulants in students between nineteen and twenty-five
years old, with higher consumption levels occurring during
final examination periods [26],[27].
The effect of modafinil on attention
Most of the research conducted on healthy adults to
investigate whether stimulants improve cognitive
performance has produced either contradictory or
inconclusive results [28]. Although modafinil plays a key
role in certain cognitive functions, such as
attention, [29],[30] and tasks that demand a certain level
of performance, it seems to have little effect when higher
exigency is taken into account [31].
Trials that have assessed attention in adults demonstrate
advantages among those taking modafinil compared to
placebo with regard to attention, using the “stop-signal
task,” [29] but this result seems to be inversely correlated
with IQ [30],[31],[32].
A study conducted with young volunteers also found
evidence of a positive effect on the “Attention Shift Task”
(a particularly demanding task) following modafinil intake.
Modafinil appears to promote the rapid switching of
attention in demanding conditions, although it offers
minimal benefit when an unpredictable and infrequent
disengagement of attention is required to respond to
alternative stimuli in an ongoing task[31].
A clinical trial with forty-five non-sleep-deprived
participants did not find conclusive results with regard to
attentional performance, possibly due to the small sample
size [33]. This finding demonstrates that the evidence in
favor of modafinil as an attention enhancer appears to be
ambiguous. This is why it is relevant to inspect the role this
substance plays with regard to certain attentional features.
In particular, selective attention (the inhibition of a
response towards irrelevant information), is a key process
for proper learning[34]. This dimension of attention has
been selected in this research due to the fact that it has
been demonstrated that impairments in selective attention
among high school and university students are usually
accompanied by low information processing and learning
capabilities, and therefore, by a deficient academic
performance [35].
Memory and executive function
Studies aiming to prove that modafinil can improve
cognitive processes such as memory and executive function
in healthy participants have been controversial,
[29],[30],[33],[36] and no systematic reviews regarding
its impact have been made available so far.
The ambiguity of these previous findings motivated the
current research. Our goal was to assess the effects of
modafinil on the cognitive performance of university
students, particularly with regard to short-term memory,
executive function, and attention.
Methods
Design
This randomized, double-blind, placebo-controlled,
crossover trial was designed to assess the effect of
modafinil (compared to placebo) on the cognitive functions
of healthy students. It was conducted at the University of
Valparaíso, Chile. The protocol was approved by the
Institutional Review Board at Faculty of Medicine
Universidad de Valparaíso under authorization code
04/2010 CEFM, and was registered on the Clinical Trials
webpage (http://clinicaltrials.gov/) under NCT code
01365897.
Participants
Eligible participants included students who were pursuing
health sciences degrees, aged eighteen to twenty-nine, and
were recruited using open advertisements on a website.
Medicine and psychology students (n=180) of both genders
were contacted, and those who met the inclusion criteria
(n=162) were recruited. The sample size was 155, and was
estimated for a two-sample comparison of means
considering (a) a two-sided significance level of p=0.05, (b)
a power (1-beta) of=0.80 and (c) an expected difference
from 19 (SD=0.7) to 19.25 (SD=0.7), and twenty percent
possible loss. The inclusion criteria were:
www.medwave.cl 3 doi: 10.5867/medwave.2015.05.6166
a) Aged between 18 and 29: This age range was chosen
because there is a normal physiological cognitive
impairment of 1% of total IQ between 25 and 29
years [37]. The purpose of this criterium was working
with a sample without cognitive deterioration, which
could modify memory performance.
b) Student in health sciences programs.
c) Healthy weight. The rationale behind this criterium
comes from the fact that all volunteers received the
same dose of modafinil; subjects outside this range
might have yielded different plasmatic levels.
The exclusion criteria were:
a) Mental disorders: Assessed by his/her clinical history or
by achieving a pathological score in Prime-MD[38].
b) Current use of psychotropic substances of any type.
c) Alcohol intake up to three days before the experiment.
d) History or symptoms of current or chronic physical
illness.
e) Pregnant or lactating women.
f) Sleep-deprived.
Outcome
The primary outcome was the attention score measured by
the proportion of correct answers on the Stroop Test.
Additional analyses were conducted that compared the
percentage of correct answers and latencies on the Stroop
Test, the Digit Span task, and the Biber Cognitive
Estimation Test in both groups.
Procedure
The participants were recruited from various courses of the
aforementioned programs and did not receive any financial
compensation. They provided informed consent, and the
self-administered Prime-MD was used to evaluate their
psychiatric conditions. Those who did not meet any
exclusion criterion were deemed eligible to participate in
this investigation. Subjects were briefly interviewed in
order to know if they were in any excluding condition
regarding sleep deprivation or substance intake
(psychotropic drugs or alcohol use).
Once the final sample was recruited, the volunteers were
appointed in randomized groups of twenty participants
each, with all twenty participants being tested
simultaneously. This was done to ensure that the tests were
properly applied, according to the conditions and capacity
of the Cognitive Psychology Laboratory of the School of
Psychology, and in order to achieve adequate plasmatic
levels of modafinil during administration of
instruments [39]. The allocation of the participants to the
experimental or control groups was performed randomly by
a computer-based allocation program, and the sequence
was concealed by the principal investigator. On day one,
participants received Substance A or B, which corresponded
to 200 mg of modafinil or a placebo (placebo pills were
made at the Faculty of Pharmacy with same shape and color
as the modafinilo pills used in this experiment). The
volunteers were assessed with the instruments 120
minutes after drug administration to attain the highest
plasmatic level [39]. The first experimental phase
evaluated attention and executive function using the Stroop
Test and the BCET, respectively. Next, we evaluated short-
term memory using the Digit Span Test. These tests were
administered on computers using MediaLab Software ©
(New York, USA). After a seven day washout period to allow
the modafinil to clear, the participants returned and were
assigned to the other arm [39]. Thus, each person received
both the modafinil and the placebo during the trial.
Instruments
Stroop Test [40]: The University of Iowa Stroop Test was
utilized, in the computerized adaptation via Medialab
software. This test requires participants to read color
names (blue, green, red, yellow) that are also printed in
color (blue, green, red, yellow). Their task is to identify the
color in which each word is printed, disregarding the
meaning of the word. There were two conditions: a
congruent condition, in which the color name and the color
of the font are the same, and an incongruent condition, in
which the color name and the color of the font are different.
The variables recorded were: answer precision (the correct
naming of the color) and response latency (in milliseconds).
This recording method yields two types of scoring: precision
and latency for both the congruent and incongruent
condition. The Stroop test primarily assesses selective
attention, given that the participant must ignore distractor
stimuli on the incongruent condition. According to a
systematic review by McLeod, [41] the Stroop Test has
been the most widely-used instrument to evaluate this
cognitive function.
Forward and Backward Digit Span [37]: The "Digit
Span" test is composed of a series of digits shown to the
volunteer and measures short-term memory span,
attentional skill, and sequencing ability. The test is
composed of two sections: forward and backward. In the
forward section, the stimuli must be repeated in sequence;
in the backward section, the stimuli must be repeated in
reverse order. The maximum score for the forward Digit
Span is 8 points, and the maximum score for the Backward
Digit Span is 7 points, which yields a total maximum score
of 15 points. This measure has high split-half reliability
(r=0.89),[42] and acceptable test-retest reliability
(r=0.80) [43].
The Biber Cognitive Estimation Test (BCET) [44]: The
BCET consists of twenty items, five items in each of the
following categories: time/duration, quantity, weight, and
distance/length. The test requires participants to
approximate the answers to questions that do not have
readily apparent answers. For example, “What is the
average length of a man’s spine?” requires the participant
to select an appropriate answer and estimate its
plausibility, but does not require complex
computation [45]. Each answer that falls within a
previously established range scores one point. The
maximum score for this test is twenty points.
Design and data analysis
We chose a randomized, crossover study design based on
the advantageous characteristic that each participant acts
as his or her own control. The allocation sequence was
www.medwave.cl 4 doi: 10.5867/medwave.2015.05.6166
concealed by the principal investigator from volunteers,
instructors, and the data analysts.
Based on the methodological design employed, we used
paired t-tests to compare means. Specifically, the analysis
compared the means obtained for each item in the
experimental and placebo condition. The statistical analysis
was performed with Stata 12.0 (Statacorp, College Station,
Texas, USA). The significance level was considered with p
<0.05.
Results
Prior to exclusion, the original sample was composed of 180
medical and psychology students, with ages between
eighteen to twenty years old. As shown in the flowchart
(figure 1) eighteen participants were not included because
of history of either mental disorders, abnormal Prime-MD
scores, or both. One hundred sixty-two participants were
randomly assigned to the groups; however, thirty-four
people did not complete the study. A final sample of 128
volunteers (76 women) completed the trial.
Figure 1: CONSORT flow diagram that graphically outlines the design and conduction of the clinical trial.
www.medwave.cl 5 doi: 10.5867/medwave.2015.05.6166
All randomized
n: 162
Completed Trial
n: 128
Age (years)
21.2 (2.55)
21.0 (2.68)
Gender
Males
Females
68 (42%)
94 (58%)
52 (41.6%)
76 (59.4%)
Height (meters)
1.67 (0.09)
1.66 (0.08)
Weight (kg)
65.9 (10.9)
65.8 (11.1)
BMI (kg/m2)
23.6 (2.93)
23.7 (2.99)
Table 1. Baseline characteristics subjects recruited for modafinil trial with means (SD).
Outcomes
1. Stroop Test: A significant difference was found
between the experimental and control groups with
regard to the proportion of correct answers in the
congruent condition (p=0.01); however, no difference
was found for the incongruent condition (p=0.81). As
shown in Table 2, there is a significantly shorter
latency for the modafinil group in the incongruent
condition (p<0.05), but no latency difference in the
congruent situation (p=0.15).
2. BCET: No significant differences were found between
the experimental and control groups with regard to the
BCET (items 0-20; p=0.26; Table 2).
3. Digit Span: The total mean score of correct answers in
the Digit Span Test did not reveal significant between-
group differences overall (p=0.26), nor were there
differences for the forward (p=0.85) and backward
(p=0.93) conditions (Table 2).
Test
Experimental group
n = 128
Control group
n = 128
(p)
Stroop test total score (correct answers)
Congruent situation
Incongruent situation
19.80 (0.47)
49.66 (6.33)
19.54 (0.72)
49.83 (4.36)
<0.01
NS
Stroop test proportion of correct answers:
Congruent situation
Incongruent situation
0.99 (0.02)
0.95 (0.12)
0.98 (0.04)
0.96 (0.08)
<0.01
NS
Stroop test latency (milliseconds)
Congruent situation
Incongruent situation
1.233 (265)
1.368 (288)
1.282 (390)
1.420 (339)
NS
0.05
BCET (score)
17.01 (2.37)
16.83 (2.06)
NS
Digit Span (score)
Forward order
Backwards order
6.40 (1.29)
6.78 (1.49)
6.43 (1.29)
6.77 (1.39)
NS
NS
Total
13.17 (2.10)
13.19 (2.22)
NS
Table 2. Comparison of values of Stroop test, BCET, and Digit Span scores between modafinil and placebo
condition, with means (SD) and p values (paired T test).
www.medwave.cl 6 doi: 10.5867/medwave.2015.05.6166
Discussion
This study showed a positive effect of modafinil on the
cognitive performance of healthy non sleep-deprived young
university students. Differences were found only with
regard to the higher precision of participants using
modafinil in the congruent condition and their shorter
latencies in the incongruent condition of the Stroop Test.
The modafinil group did not show advantages over the
placebo group with regard to short-term memory or
executive function.
Considering that the major strength of this work is
methodological because the crossover design is robust in
pharmacological evaluations--as long as drug clearance can
be assured--this research addresses a phenomenon that, in
our opinion, is highly relevant to university students. Health
and education policies should consider the possible abuse
of this drug, given the belief that it optimizes studying
performance.
We found significant between-group differences with regard
to Stroop Test performance in the congruent condition, but
not in the incongruent condition. These results are
inconsistent with previous findings [30][31],[32][31],[46].
We believe that this discrepancy is due to several
differences (i.e., sample size, age range, sleep-deprivation
status, experimental protocols, etc) that make it difficult to
compare our results with those of other studies.
Given that the congruent condition demands less cognitive
resources than the incongruent condition, this result
confirms that modafinil enhances selective attentional
performance when the task has low cognitive exigency. This
result conflicts with those reported by Marchant, who
reported that participants using modafinil attained a better
specific performance on the Attention Shift Task for both
constant and alternating condition (the latter of which has
a high level of difficulty). However, this task is not directly
comparable to the Stroop Test. Marchant states that the
Attention Shift Task mimics an event-based prospective
memory (PM), which requires a person to interrupt an
ongoing activity to retrieve and act upon a previously
formed intention [31]. In a standard PM task, participants
exhibit distinct responses when they recognize new targets
that are associated with a previously formed intention.
These targets appear relatively infrequently and draw
attentional resources. Given that modafinil increases
arousal and that heightened arousal has been shown to
improve sustained attention, attention switching, and
PM, [31] this drug may improve performance in PM-like
tasks such as Attention Shifting Task, but not regarding
selective attention.
In contrast to this result, several studies have
demonstrated a lack of physiological or subjective effects
of modafinil on arousal. However, they have observed an
increase in cognitive function [11],[32],[47],[48],[49]. In
principle, attention-shifting requires similar resources to
PM. In fact, the literature tends to assume that PM and
task-switching capabilities are governed by the same brain
regions (i.e. the prefrontal cortex)[50],[51]. However,
whereas one requires continuous, rapid shifts of attention,
the other requires disengagement from an attention-
demanding task to successfully detect and respond to a
rarely occurring target at the appropriate time.
This observation is not surprising, and it parallels the
inconclusive results of Randall, possibly due to modafinil's
best effect when used for disadvantageous conditions (e.g.,
illness or sleep deprivation), and to restore the basal
cognitive level [33]. This means that it allows the nervous
system to function and attain full arousal levels, but there
is no evidence for cognition improvement in an already
awakened individual.
An unexpected finding of our trial was that the Stroop Test
latency in the incongruent condition was significantly
shorter in the modafinil group compared to the control
group. Thus, modafinil does not improve precision but it
does shorten reaction time in the incongruent condition.
The participants did not show significant between- group
differences with regard to working memory or executive
function. Although our results diverge with those of Turner
and Randall [29],[32],[46], they agree with those of
Baranski, et al. and Müller [30],[36]. This result may be
due to the effects of modafinil being mediated by a plethora
of variables that have not been fully studied (particularly
IQ) [52].
The benefits of modafinil on different memory and
executive function for people with sleep disorders or
pathologies that involve attention impairment appear
irrefutable [1], but our goal to make results more
generalizable to healthy populations remains ambiguous
and requires further research.
Although participants were told to be well-rested, they may
have misreported, or they may have had sleep disorders.
Therefore, a potential limitation of this study is that sleep
quality was not assessed with the exception of the briefing
protocol. It must be considered that our design and the
large sample size allowed us to detect very significant
statistical differences regarding the Stroop test; whether
these statistical differences are clinically relevant may be
debatable.
With regard to the ecological validity of this study, it should
be noted that modafinil is consumed by students in order
to improve academic performance. For this reason, studies
like the current trial, which assess the effectiveness of this
drug using tasks that assess studying abilities, are
pertinent. Nevertheless, it is advisable to complement this
research with investigations directed toward other aspects
of memory and executive function.
As a conclusion, modafinil does not enhance the global
cognitive performance of healthy non-sleep-deprived
students, except regarding non-demanding tasks. In
particular, this drug does not seem to have positive effects
on the basic mental processes that sustain studying tasks
in the college population under normal conditions. We
expect these findings to demystify the use of this drug and
help decision making concerning pharmacological public
policies.
www.medwave.cl 7 doi: 10.5867/medwave.2015.05.6166
Notes
Conflicts of Interests
The authors have completed the conflict of interests
declaration form from the ICMJE, and declare not having
any conflict of interests with the matter dealt herein. Forms
can be requested to the responsible author or the editorial
direction of the Journal.
Ethical issues
Participants signed an informed consent form. The protocol
was approved by the Institutional Review Board at Faculty
of Medicine Universidad de Valparaíso under authorization
code 04/2010 CEFM, and was registered on the Clinical
Trials website (http://clinicaltrials.gov/) under code
NCT01365897.
Institutional Support
Dirección de Investigación de la Universidad de Valparaíso
- Grant 05/2006.
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