Modafinil, but not escitalopram, improves working memory and sustained attention in long-term, high-dose cocaine users

Kalechstein, Ari D.; Mahoney, James J.; Yoon, Jin Ho; Bennett, R.; Garza, Richard De La

doi:10.1016/j.neuropharm.2012.06.064

Cited by 47 publications

(33 citation statements)

References 34 publications

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“…In addition, treatment with 200 mg modafinil has been found to attenuate the subjective effects produced by methamphetamine (De La Garza et al, 2010) and to improve cognitive function in both healthy participants (Turner et al, 2003) and in cocaine-dependent individuals (Kalechstein et al, 2013). Absorption of modafinil is rapid, with peak plasma concentrations occurring at ~2–4 hours.…”

Section: Methodsmentioning

confidence: 99%

“…This approach was based logically on the ability of cocaine to acutely increase intrasynaptic DA to supraphysiological levels, via blockade of the DA transporter (DAT; Volkow et al, 2002), which correlates with both the positive subjective effects (Volkow et al, 1997) as well as the reinforcing effects (Hart et al, 2008) produced by cocaine. Further, long-term cocaine use appears to cause neuroadaptations within the mesocorticolimbic system (Verrico et al, 2013), including cortical hypofrontality and reduced dopaminergic neurotransmission, which have been associated with deficits in executive functioning (Groman and Jentsch, 2012; Kalechstein et al, 2003), poor treatment response (Martinez et al, 2011), and an increased vulnerability to relapse (Sofuoglu, 2010). …”

Section: Introductionmentioning

confidence: 99%

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Treatment with modafinil and escitalopram, alone and in combination, on cocaine-induced effects: A randomized, double blind, placebo-controlled human laboratory study

Verrico

Haile

Mahoney

et al. 2014

Drug and Alcohol Dependence

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Background Concurrent administration of dopamine and serotonin reuptake inhibitors reduces cocaine self-administration in monkeys. Consonant with this, clinical trials assessing modafinil and selective serotonin reuptake inhibitors alone show some efficacy as potential pharmacotherapies for cocaine dependence. We hypothesized that combining modafinil with escitalopram would attenuate the euphoric effects of cocaine to a greater degree than modafinil alone. Methods In a randomized, double blind, parallel groups design participants received either placebo (0 mg/day; n = 16), modafinil (200 mg/day; n = 16), escitalopram (20 mg/day; n = 17), or modafinil+escitalopram (200+20 mg/day; n = 15) for 5 days. On day 5, during separate sessions participants received an intravenous sample of cocaine (0 or 20mg; randomized) and five $1 bills. Participants rated the subjective effects of the infusions and subsequently made choices to either return $1 and receive another infusion or keep $1 and receive no infusion. Results Compared to saline, cocaine (20mg) significantly (p ≤ 0.008) increased most ratings, including “Good Effects”, “Stimulated”, and “High”. Relative to placebo, modafinil significantly (p ≤ 0.007) attenuated subject-rated increases of “Any Drug Effect”, “High”, “Good Effects”, and “Stimulated” produced by cocaine. Compared to saline, participants chose cocaine infusions significantly more; however, no treatment significantly reduced choices for cocaine infusions. Escitalopram did not enhance the efficacy of modafinil to reduce any measure. Conclusions Modafinil attenuated many positive subjective effects produced by cocaine; however, escitalopram combined with modafinil did not enhance the efficacy of modafinil to reduce cocaine effects.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment with modafinil and escitalopram, alone and in combination, on cocaine-induced effects: A randomized, double blind, placebo-controlled human laboratory study

Verrico

Haile

Mahoney

et al. 2014

Drug and Alcohol Dependence

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“…In an inpatient study, patients with cocaine dependence were randomized to receive 200 mg/day modafinil (n=16), 20 mg/day escitalopram (n=16), modafinil plus escitalopram (n=15), or placebo (n=14) for 5 days. Modafinil treatment, but not escitalopram, modafinil plus escitaloram, or placebo, improved working memory function (Kalechstein, Mahoney, Yoon, Bennett, & De la Garza, 2013). Several randomized clinical trials have also found some support for modafinil’s efficacy in reducing cocaine use in various groups (Anderson et al, 2009; Dackis, Kampman, Lynch, Pettinati, & O’Brien, 2005; Dackis et al, 2012).…”

Section: Treatment Approaches Targeting Cognitive Functionsmentioning

confidence: 99%

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders

Sofuoglu

DeVito

Waters

et al. 2016

Journal of Dual Diagnosis

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Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive control and include cholinesterase inhibitors (e.g., galantamine, rivastigmine) and monoamine transporter inhibitors (e.g., modafinil, methylphenidate). Cognitive behavioral therapy and cognitive rehabilitation also enhance executive control, while cognitive bias modification targets impairments associated with automatic processes. Cognitive enhancements to improve treatment outcomes is a novel and promising strategy, but its clinical value for the treatment of stimulant use disorder, with or without other psychiatric comorbidities, remains to be determined in future studies.

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“…A wake-promoting agent, modafinil is FDA approved for the treatment of several sleep disorders including narcolepsy. Modafinil has also been shown to benefit working memory and attention in in persons with cocaine dependence who were not alcohol dependent (Kalechstein et al, 2013), and when given in the morning has a normalizing effect on sleep architecture in this population (Morgan et al, 2007, 2010). These effects on treatment outcome, cognition and sleep may be interrelated: for instance, changes in sleep architecture during abstinence and laboratory cocaine use correspond with sleep-dependent cognitive performance (Morgan et al, 2006, 2008).…”

Section: Introductionmentioning

confidence: 99%

Preliminary evidence for normalization of risk taking by modafinil in chronic cocaine users

Canavan

Forselius

Bessette

et al. 2014

Addictive Behaviors

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Modafinil, a wake-promoting agent used to treat sleep disorders, is thought to enhance cognition. Although modafinil has shown promise as a pharmacotherapy for the treatment of cocaine dependence, it is unknown to what extent cognitive effects may play a role in such treatment. We examined the effect of modafinil on the Balloon Analogue Risk Task (BART), a behavioral measure in which higher scores are purported to reflect a greater propensity for risk-taking. Thirty cocaine dependent individuals, enrolled in a randomized clinical trial of modafinil 400mg (n=12) versus placebo (n=18), were administered the BART during the second week of inpatient treatment for cocaine dependence. A comparison cohort of healthy participants (n=19) performed the BART under similar conditions. Modafinil treatment was associated with significantly higher BART scores (p=0.01), which were comparable to scores in healthy persons. BART scores in placebo treated participants were much lower than previously reported in healthy participants, and lower than those observed in the comparison cohort. As propensity toward risk taking is typically associated with higher BART scores as well as increased risk for substance use, our findings may reflect a novel aspect of cognitive impairment related to chronic cocaine use. Notably, the low BART scores reflect highly suboptimal performance on the task, and the observed effect of modafinil may indicate a normalization of this impairment and have implications for treatment outcome.

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Modafinil, but not escitalopram, improves working memory and sustained attention in long-term, high-dose cocaine users

Cited by 47 publications

References 34 publications

Treatment with modafinil and escitalopram, alone and in combination, on cocaine-induced effects: A randomized, double blind, placebo-controlled human laboratory study

Treatment with modafinil and escitalopram, alone and in combination, on cocaine-induced effects: A randomized, double blind, placebo-controlled human laboratory study

Cognitive Function as a Transdiagnostic Treatment Target in Stimulant Use Disorders

Preliminary evidence for normalization of risk taking by modafinil in chronic cocaine users

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