The effects of modafinil treatment on neuropsychological and attentional bias performance during 7-day inpatient withdrawal from methamphetamine dependence.

Abstract

The cognitive benefits of modafinil to patients undergoing 7-day inpatient withdrawal from methamphetamine (MA) dependence were examined as part of a double-blind, randomized, placebo-controlled pilot trial. Recent evidence has identified modafinil-related improvements in treatment outcomes for MA-dependent patients; however, the benefits to cognition function, which is critical to treatment success but known to be impaired, has yet to be examined. The first 20 participants recruited to the study were administered either 200 mg of modafinil (once daily) or placebo, and a neuropsychological test battery (including an MA version of the emotional Stroop task) at admission (n ϭ 17) and discharge (n ϭ 14). Follow-up interviews were conducted at 1-month postdischarge (n ϭ 13). After participant withdrawals (3 in each group), treatment was associated with a significant improvement in immediate verbal memory recall and nonsignificant trend toward improvement on executive function and delayed memory tasks. No benefit was seen for measures of verbal learning, visual memory, processing speed, or verbal fluency. All participants showed a significant attentional bias for MA-related stimuli on the emotional Stroop task. The magnitude of bias predicted both retention in treatment and relapse potential at follow-up but was not significantly ameliorated by modafinil treatment. While nonsignificant, the effect sizes of modafinil-related improvements in executive function and memory were consistent with those found in more robustly powered studies of cognitive benefits in attention-deficit/hyperactivity disorder and schizophrenia, supporting the need for further research.

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans

“…Although this dose has been shown to improve cognitive function in other MA-dependent, psychiatric, and healthy subject samples (Hester et al, 2010;Müller et al, 2004;Turner et al, 2003Turner et al, , 2004aTurner et al, , 2004bWalsh et al, 2004), higher doses (e.g., 400 mg) have been shown to be safe in MA-dependent participants (Heinzerling et al, 2010) and may produce a more pronounced cognitive effect. In addition, compared with our single-dose design, use of a multiple-dose design would have been preferable for the detection of a dose-response relationship between modafi nil and cognitive performance.…”

“…In a human laboratory study, several acute doses of modafi nil (150, 300, and 450 mg) did not significantly modify inhibitory control in cocaine users (n = 11), although the go/no-go task used in this study may not have been optimized to detect improvements in inhibitory control (Vansickel et al, 2008). In a small, between-subjects, inpatient study, immediate verbal memory was improved in MA-dependent participants receiving modafi nil (200 mg; n = 7) relative to those receiving placebo (n = 7) (Hester et al, 2010), but differences between the groups were not observed on measures of visual memory, processing speed, or verbal fl uency. Last, in a small study of MA-dependent subjects (n = 11; Kalechstein et al, 2010), modafi nil (400 mg) did not have a signifi cant effect on working memory and learning/memory performance across subjects.…”

“…Although the effect of modafi nil on cognition has been somewhat equivocal in individuals with stimulant use disorders (Hester et al, 2010;Kalechstein et al, 2010;Vansickel et al, 2008), the sample sizes of these studies have generally been small (~10 participants receiving modafi nil). The present study was therefore performed to test the effects of modafi nil on the cognitive functioning of MA-dependent (n = 24) and healthy (n = 17) subjects in a randomized, doubleblind, within-subjects study.…”

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders

“…In a small inpatient study, 7 days of modafinil treatment improved immediate verbal memory function in 14 patients with methamphetamine dependence who were undergoing 7-day withdrawal (Hester, Lee, Pennay, Nielsen, & Ferris, 2010). In another study, 3 days of modafinil (400 mg/day) treatment improved working memory function in individuals with methamphetamine dependence (n=11) who had impaired working memory function at baseline (Kalechstein, De La Garza, & Newton, 2010).…”

Impulsivity and attentional bias as predictors of modafinil treatment outcome for retention and drug use in crack-cocaine dependent patients: Results of a randomised controlled trial

“…Modafinil improved verbal memory recall after 5 days of administration (Hester et al, 2010); and modafinil-related improvements in working memory were found in a subgroup of methamphetamine-dependent volunteers with poor baseline performance, as compared with high performers, after 3 days of administration (Kalechstein et al, 2010). In two other studies, a single dose of modafinil was associated with overall improvements in learning performance (Ghahremani et al, 2011), and in inhibitory control and processing speed in a subgroup of methamphetamine-dependent patients with high baseline frequency methamphetamine use, versus a subgroup with low baseline frequency methamphetamine use (Dean et al, 2011).…”