Modafinil increases the latency of response in the Hayling Sentence Completion Test in healthy volunteers: a randomised controlled trial

Abstract

Background: Modafinil is a medication licensed for the treatment of narcolepsy. However, it has been reported that healthy individuals without wakefulness disorders are using modafinil off-label to enhance cognitive functioning. Although some studies have reported that modafinil improves cognitive task performance in healthy volunteers, numerous other studies have failed to detect cognitive enhancing effects of modafinil on several well-established neuropsychological tasks. Interestingly, several clinical and preclinical studies have found that improved cognitive task performance by modafinil is accompanied by slower response times. This observation raises the question as to whether this slowing of response time in healthy volunteers is a necessary and sufficient condition for cognitive enhancement with modafinil. The aim of the current experiment was to explore this question by investigating the effects of modafinil on the Hayling Sentence Completion Test (HSCT).

Methodology: Sixty-four healthy volunteers received either a single dose (200 mg) of modafinil (n = 32) or placebo (n = 32) in a randomized, double-blind, placebo-controlled, parallel group study in which the principal outcome measures were response latencies on the response initiation and response inhibition sections of the HSCT.

Principal findings: Participants dosed with modafinil had significantly longer mean response latencies on the HSCT for both the response initiation and response inhibition compared to participants dosed with placebo. However, participants in both groups made a similar number of errors on each of these measures, indicating that modafinil did not enhance the accuracy of performance of the task relative to placebo.

Conclusions: This study demonstrated that administration of single 200 mg doses of modafinil to healthy individuals increased the latency of responses in the performance of the HSCT, a task that is highly sensitive to prefrontal executive function, without enhancing accuracy of performance. This finding may provide important clues to defining the limitations of modafinil as a putative cognitive enhancer.

Trial registration: ClinicalTrials.gov NCT02051153.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. CONSORT Diagram.

Flow diagram graphically describes the design of the study: enrolment, intervention, follow-up and data analysis.

Figure 2. Latency.

The figure depicts the effect of drug on the response latency in the performance of the Hayling Sentence Completion Task (HSCT). There was a significant effect of drug on latency in the completion of the task across sections, with modafinil-treated participants having longer response latencies across test sections (p = 0.035) **. Error bars represent the SEM.

Figure 3. Errors.

The figure depicts the effect of drug on errors in the performance of the Hayling Sentence Completion Task (HSCT). There was a significant effect of test section on errors committed during the task, with participants across treatment groups making more errors in the response inhibition section of the task relative to the response initiation section of the task. **P