Stimulant May Reduce 'Sluggish Cognitive Tempo' in Adults With ADHD

Jennifer Lubell

July 01, 2021

A stimulant used in patients with attention-deficit/hyperactivity disorder might prove useful for other comorbid symptoms, results of a randomized, crossover trial suggest.

In the trial, the investigators reported that lisdexamfetamine (Vyvanse) reduced self-reported symptoms of sluggish cognitive tempo (SCT) by 30%, in addition to lowering ADHD symptoms by more than 40%.

The drug also corrected deficits in executive brain function. Patients had fewer episodes of procrastination, were better able to prioritize, and showed improvements in keeping things in mind.

"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," Lenard A. Adler, MD, the lead author, said in a press release. The results were published June 29, 2021, in the Journal of Clinical Psychiatry.

The trial is groundbreaking because it is the first treatment study for ADHD with SCT in adults, Adler, director of the adult ADHD program at New York University Langone Health, said in an interview. He said that Russell A. Barkley, PhD, a clinical professor of psychiatry at Virginia Commonwealth University, Richmond, defines SCT as having nine cardinal symptoms: prone to daydreaming, easy boredom, trouble staying awake, feeling foggy, spaciness, lethargy, underachieving, less energy, and not processing information quickly or accurately.

Barkley, who studied more than 1,200 individuals with SCT, discovered that nearly half also had ADHD, Adler said. Those with the comorbid symptoms also had more impairment.

Whether or not the symptom set of SCT is a distinct disorder or a cotraveling symptom set that goes along with ADHD has been an area of investigation, said Adler, also a professor in the departments of psychiatry and child and adolescent psychiatry at New York University. Other known comorbid symptoms include executive function deficits and trouble with emotional control.

Stimulants to date have only shown success in children, as far as improving SCT. The goal of this study was to determine the efficacy of lisdexamfetamine on the nature and severity of ADHD symptoms and SCT behavioral indicators in adults with ADHD and SCT.

Two Cohorts, Alternating Regimens

The investigators enrolled 38 adults with DSM-5 ADHD and SCT. Patients were recruited from two academic centers, New York University and the Icahn School of Medicine at Mount Sinai. The randomized 10-week crossover trial included two double-blind treatment periods, each 4 weeks long, with an intervening 2-week, single-blind placebo washout period.

"In crossover design, patients act as their own control, because they receive both treatments," Adler said. Recruiting a smaller number of subjects helps to achieve significance in results.

For the first 4 weeks, participants received daily doses of either lisdexamfetamine (30-70 mg/day; mean, 59.1 mg/day) or a placebo sugar pill (mean, 66.6 mg/day). Researchers used standardized tests for SCT signs and symptoms, ADHD, and other measures of brain function to track psychiatric health on a weekly basis. After a month, the two cohorts switched regimens – those taking the placebo started the daily doses of lisdexamfetamine, and the other half stopped the drug and started taking the placebo.

Primary outcomes included the ADHD Rating Scale and Barkley Adult ADHD Rating Scale-IV SCT subscale.

Compared with placebo, adults with ADHD and comorbid SCT showed significant improvement after taking lisdexamfetamine in ratings of SCT and total ADHD symptoms. This was also true of other comorbid symptoms, such as executive function deficits.

In the crossover design, patients who received the drug first hadn't gone fully back to baseline by the time the investigators crossed them over into the placebo group. "So, we couldn't combine the two treatment epochs," Adler said. However, the effect of the drug versus placebo was comparable in both study arms.

SCT Alone Was Not Studied

The trial had some limitations, mainly that it was an initial study with a modest sample size, Adler said. It also did not examine SCT alone, "so we can't really say whether the stimulant medicine would improve SCT in patients who don't have ADHD. What's notable is when you look at how much of the improvement in SCT was due to improvement in ADHD, it was just 25%." This means the effects occurring on SCT symptoms were not solely caused by effects on ADHD.

"We can't say definitively that patients without SCT would respond to a stimulant. That's a subject for future study," he said.

Adler would like to see treatment studies of adults with ADHD and SCT in a larger sample, potentially with other stimulants. In addition, future trials could examine the effects of stimulants on adults with SCT that do not have ADHD.

The results of this trial underscore the importance of evaluating adults with ADHD for comorbid symptoms, such as executive function and emotional control, he continued. "Impairing SCT symptoms may very well fall under that umbrella," Adler said. "If you don't identify them, you can't track them in terms of treatment."

SCT as a "Flavor" of ADHD

The outcome of this study demonstrates that lisdexamfetamine significantly improves both ADHD symptoms and SCT symptoms, said David W. Goodman MD, LFAPA, an assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore.

Goodman, who was not involved in the study, agreed that clinicians should be aware of SCT when assessing adults with ADHD and conceptualize SCT as a "flavor" of ADHD. "SCT is not widely recognized by clinicians outside of the research arena but will likely become an important characteristic of ADHD presentation," he said in an interview.

"Future studies in adult ADHD should further clarify the prevalence of SCT in the ADHD population and address more specific effective treatment options," he said.

James M. Swanson, PhD, who also was not involved with the study, agreed in an interview that it documents the clear short-term benefit of stimulants on symptoms of SCT. The study "may be very timely, since adults who were affected by COVID-19 often have residual sequelae manifested as 'brain fog,' which resemble SCT," said Swanson, professor of pediatrics at the University of California, Irvine.

The study was funded by Takeda Pharmaceutical, manufacturer of lisdexamfetamine. Adler has received grant/research support and has served as a consultant from Shire/Takeda and other companies. Goodman is a scientific consultant to Takeda and other pharmaceutical companies in the ADHD arena. Swanson had no disclosures.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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