Lisdexamfetamine reduces symptoms of sluggish cognitive tempo in adults with ADHD

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Tests of a drug known to stimulate brain activity have shown early success in reducing symptoms of sluggish cognitive tempo in 38 men and women with attention deficit hyperactivity disorder (ADHD.)

A collection of symptoms including persistent dreaminess, fatigue, and slow-working speed, sluggish cognitive tempo has been a subject of debate over whether it is part of, or separate from, ADHD.

Researchers at NYU Grossman School of Medicine and Icahn School of Medicine at Mount Sinai who led the study say the stimulant lisdexamfetamine (sold as Vyvanse) reduced by 30 percent self-reported symptoms of sluggish cognitive tempo.

It also lowered by over 40 percent symptoms of ADHD and significantly corrected deficits in executive brain function, with fewer episodes of procrastination, improvements in keeping things in mind, and strengthened prioritization skills.

Publishing in the Journal of Clinical Psychiatry online June 29, the study also showed that one-quarter of the overall improvements in sluggish cognitive tempo, such as feelings of boredom, trouble staying alert, and signs of confusion, were due to improvements in symptoms of ADHD.

The team interpreted that outcome to mean that decreases in ADHD-related incidents of physical restlessness, behaving impulsively, and/or moments of not paying attention were linked to some but not all of the improvements in sluggish cognitive tempo.

“Our study provides further evidence that sluggish cognitive tempo may be distinct from attention deficit hyperactivity disorder and that the stimulant lisdexamfetamine treats both conditions in adults, and when they occur together,” says lead study investigator and psychiatrist Lenard Adler, MD.

Adler, who directs the adult ADHD program at NYU Langone Health, says until now stimulants have only been shown to improve sluggish cognitive tempo symptoms in children with ADHD. The NYU Langone-Mount Sinai team’s findings, he adds, are the first to show that such treatments also work in adults.

A professor in the Departments of Psychiatry and Child and Adolescent Psychiatry at NYU Langone, Adler says sluggish cognitive tempo is likely a subset of symptoms commonly seen in some patients with ADHD and other psychiatric disorders. However, it remains unclear if sluggish cognitive tempo is a distinct psychiatric condition on its own and if stimulant medications will improve sluggish cognitive tempo in patients without ADHD.

Some specialists have been seeking to qualify sluggish cognitive tempo as distinct, but critics say more research is needed to settle the question.

“These findings highlight the importance of assessing symptoms of sluggish cognitive tempo and executive brain function in patients when they are initially diagnosed with ADHD,” says Adler.

For the study, funded by the drug manufacturer, Takeda Pharmaceuticals of Cambridge, Mass., several dozen volunteer participants received daily doses of either lisdexamfetamine or a placebo sugar pill for one month. Researchers then carefully tracked their psychiatric health on a weekly basis through standardized tests for signs and symptoms of sluggish cognitive tempo, ADHD, as well as other measures of brain function.

Study participants then switched roles: The one-half who had been taking the placebo started taking daily doses of lisdexamfetamine, while the other half who had been on the drug during the study’s first phase started taking the placebo.

Adler has received grant and/or research support from Sunovion Pharmaceuticals, Enymotec, Shire Pharmaceuticals (now part of Takeda), Otsuka, and Lundbeck. He has also served as a paid consultant to these companies, in addition to Bracket, SUNY, the National Football League, and Major League Baseball. He has also received royalty payments since 2004 from NYU for adult ADHD diagnostic and training materials. All of these relationships are being managed in accordance with the policies and procedures of NYU Langone.

Besides Adler, other NYU Langone researchers involved in the study are Terry Leon, MS, RN; Taylor Sardoff, BA; and Michael Silverstein, MS. Other investigators include Beth Krone, PhD; and Jeffrey Newcorn, MD, at Icahn School of Medicine at Mount Sinai in New York City; and Stephen Faraone, PhD, at SUNY Upstate Medical University in Syracuse, NY.


Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with an estimated worldwide prevalence in children and adolescents of ∼5% (Polanczyk et al. 2007). ADHD often persists beyond childhood, with a reported prevalence in adults in the range of 3%–5% across different countries (Fayyad et al. 2007; Simon et al. 2009). In Europe, methylphenidate (MPH) is the only psychostimulant licenced and recommended by guidelines as first-line therapy for the treatment of children and adolescents with ADHD (National Institute for Health and Care Excellence [NICE] 2018).

In North America, amphetamines (AMPs) are recommended additionally as a first-line treatment (AAP 2011; CADDRA 2018). In Europe and North America, lisdexamfetamine dimesylate (LDX) and MPH are both licenced and recommended to be used in first-line treatment of adults with ADHD (AAP 2011; CADDRA 2018; NICE 2018). Evidence from a recent network meta-analysis supports MPH (in children and adolescents) and AMPs (in adults) as the preferred first choice for short-term pharmacological treatment of ADHD (Cortese et al. 2018). This concurs partly with the NICE (2018) recommendations.

The efficacy of the long-acting AMP prodrug LDX in relieving the symptoms of ADHD has been demonstrated in a series of pivotal randomized controlled trials in North America and Europe (Biederman et al. 2007; Adler et al. 2008; Findling et al. 2011; Coghill et al. 2013). Evidence from trials of at least 12-month duration indicates that the safety and tolerability profile of LDX is similar to those of other stimulants in people with ADHD (Findling et al. 2008; Weisler et al. 2009; Coghill et al. 2014).

LDX was first approved in the United States for the treatment of ADHD in children and adolescents in 2007 (Vyvanse Shire US, Inc. 2016), followed in 2013 in certain European countries for the treatment of children and adolescents with ADHD whose response to previous MPH treatment was considered clinically inadequate (Elvanse: Shire Pharmaceuticals Ltd. 2016b). Since then, LDX has also been approved for the treatment of adults with ADHD in several European countries, including the treatment of adults not older than 55 years in Switzerland (2014) and all adults in Denmark, Sweden, and the United Kingdom (2015) (Elvanse Adult: Shire Pharmaceuticals Ltd 2016a). The NICE guidelines in the United Kingdom include LDX in the recommendation for first-line pharmacological treatment of adult ADHD (NICE 2018).

However, there is little evidence of how the treatment is being used in terms of patient characteristics and prescribing patterns in the real world. Drug utilization studies are important to understand the use of a treatment in routine clinical practice. Previous drug utilization studies have shown that treatment adherence and persistence are generally greater for long-acting stimulants than for short-acting stimulants, and that adherence to, and persistence with, AMP treatment is greater than for MPH treatment (Christensen et al. 2010; Lawson et al. 2012).

Since its approval in Europe in 2013, published information related to the use of LDX in the real-world setting has been lacking. The objective of this retrospective, European safety study was to evaluate drug utilization patterns and monitor off-label use of LDX in the 5 years since LDX was first launched in the region as part of Shire’s ongoing pharmacovigilance programme for LDX; this study was not intended to compare the safety of LDX with other drugs for the treatment of ADHD. This includes the characterization of patients, description of LDX prescribing patterns among physicians and usage patterns among patients, and potential off-label use.

reference link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475084/


Original Research: The findings will appear in Journal of Clinical Psychiatry

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