Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder

doi:10.1016/j.biopsych.2004.02.008

Biological Psychiatry

Volume 55, Issue 10, 15 May 2004, Pages 1031-1040

https://doi.org/10.1016/j.biopsych.2004.02.008 Get rights and content

Abstract

Background

Modafinil, a novel cognitive enhancer, has a clinical profile similar to conventional stimulants such as methylphenidate, despite a seemingly different mechanism of action. Modafinil selectively improves neuropsychological task performance in healthy volunteers, possibly through improved inhibitory control. We examined whether modafinil induced similar improvements in adults with attention-deficit/hyperactivity disorder.

Methods

Twenty patients with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were entered into a double-blind, randomized, placebo-controlled crossover study using a single 200 mg dose of modafinil.

Results

Modafinil produced a similar pattern of cognitive enhancement to that observed in healthy adults, with improvements on tests of short-term memory span, visual memory, spatial planning, and stop-signal motor inhibition. On several measures, increased accuracy was accompanied by slowed response latency. This alteration in the speed-accuracy trade-off may indicate that modafinil increases the ability to “reflect” on problems coupled with decreased impulsive responding. Improvements were also seen in sustained attention, which was unaffected in healthy subjects.

Conclusions

If these benefits are shown to be maintained with chronic administration, modafinil may have potential as an important therapy for attention-deficit/hyperactivity disorder with a similar effect to stimulants such as methylphenidate in improving stop-signal response inhibition but without the side effects commonly experienced with amphetaminelike drugs.

Section snippets

Patients and procedures

Twenty patients (seven female) meeting criteria for a DSM-IV diagnosis of ADHD (American Psychiatric Association 1994) were recruited from patients attending a specialized psychiatric clinic for the assessment of suspected ADHD in adults. They had a mean age of 28 ± 9 years, an average National Adult Reading Test (NART) verbal intelligence quotient (IQ) (Nelson 1982) of 108 ± 6, and had been in education for an average of 14 ± 2 years (Table 1). The study was approved by the Cambridge Local

Physiologic effects—blood pressure and pulse

Physiologic effects of modafinil were apparent for pulse (drug × time interaction) [F(3,54) = 4.07, p = .011], with a marginally nonsignificant effect on systolic blood pressure [F(3,54) = 2.58, p = .063]. In both cases, modafinil attenuated the natural decrease in heart rate and systolic blood pressure seen over the testing session (Figure 1). Modafinil also increased diastolic blood pressure over all time points (main effect of drug) [F(1,18) = 5.28, p = .034) and showed a trend toward a

Discussion

The results of this study demonstrate that in adult ADHD, modafinil is associated with a pattern of cognitive enhancement similar to that seen in healthy controls (Turner et al 2003). Modafinil improved performance on tests of digit span, visual memory (delayed PRM and DMTS), spatial planning (NTOL), decision-making (Gamble), and SSRT. These effects were accompanied by a slowing in latency with modafinil on the NTOL task and trends toward slower latency on the delayed PRM and DMTS tasks. This

Acknowledgements

DCT was funded by a Research Studentship from the Medical Research Council of the United Kingdom. BJS and TWR are consultants for Cambridge Cognition Ltd.

We thank the patients for participating in this study, which was funded by a Wellcome Trust Program grant awarded to Professors T.W. Robbins, B.J. Everitt, B.J. Sahakian, and Dr. A.C. Roberts and completed within the Medical Research Council (United Kingdom) Center for Behavioral and Clinical Neuroscience.

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Original articleModafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder

Abstract

Background

Methods

Results

Conclusions

Section snippets

Patients and procedures

Physiologic effects—blood pressure and pulse

Discussion

Acknowledgements

Neurosci Lett

Biol Psychiatry

Cell

J Am Acad Child Adolesc Psychiatry

Sleep Med

Brain Cogn

Biol Psychiatry

Biol Psychiatry

Neurosci Lett

Neurosci Lett

Brain Res

Neuropsychologia

Neuropsychologia

Neuropharmacology

Neurotoxicol Teratol

Trends Cogn Sci

J Am Acad Child Adolesc Psychiatry

Pediatr Neurol

Cell

Behav Brain Res

Arch Clin Neuropsychol

Diagnostic and Statistical Manual of Mental Disorders

Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans

Nat Neurosci

Attention Deficit Hyperactivity DisorderA Handbook for Diagnosis and Treatment

Attention Deficit Hyperactivity Disorder. A Clinical Workbook

Abnormal executive function in attention deficit hyperactivity disorderThe effect of stimulant medication and age on spatial working memory

Psychol Med

The somatic marker hypothesis and decision-making

ModafinilA double-blind multicentric study

Sleep

The use of analogue scales in rating subjective feelings

Br J Med Psychol

Practice and difficulty evoke anatomically and pharmacologically dissociable brain activation dynamics

Cereb Cortex

A double-blind, placebo-controlled investigation of the efficacy of modafinil for sustaining the alertness and performance of aviatorsA helicopter simulator study

Psychopharmacology (Berl)

Neuroscience of attention-deficit/hyperactivity disorderThe search for endophenotypes

Nat Rev Neurosci

Study of the addictive potential of modafinil in naive and cocaine-experienced rats

Psychopharmacology (Berl)

Brief Symptom Inventory (BSI)Administrative, Scoring and Procedural Manual

Effects of methylphenidate on spatial working memory and planning in healthy young adults

Psychopharmacology (Berl)

Neuropsychological assessment of response inhibition in adults with ADHD

J Clin Exp Neuropsychol

Varieties of impulsivity

Psychopharmacology (Berl)

Meta-analysis of the efficacy of methylphenidate for treating adult attention-deficit/hyperactivity disorder

J Clin Psychopharmacol

The diagnosis and neuropsychological assessment of adult attention deficit/hyperactivity disorder. Scientific study and practical guidelines

Ann N Y Acad Sci

Original article
Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder