REVIEW OF: Adler LA et al, J Clin Psychiatry 2021;82(4):20m13687

STUDY TYPE: Randomized placebo-controlled trial

Patients with ADHD often also struggle with sluggish cognitive tempo (SCT). Characteristics of SCT include being prone to daydreaming, being easily bored, feeling “spacey” or lethargic, and not processing information quickly or accurately. This diagnosis—which is not found in the DSM—is controversial, and it has the most support when it occurs as a comorbidity of ADHD.

Studies of methylphenidate and atomoxetine have shown some improvement in SCT among youth with ADHD. This industry-sponsored study, which used lisdexamfetamine (Vyvanse), is the first stimulant trial for SCT in adults.

The investigators recruited 39 adults with comorbid ADHD and SCT. This was a “clean” cohort, meaning that no one had another active psychiatric disorder and no one had a lifetime history of bipolar disorder. The trial used a crossover design, in which all patients received either stimulant or placebo over a four-week treatment block, then everyone underwent a two-week washout period before switching to the other group in a second four-week treatment block. Lisdexamfetamine was started at 30 mg daily and titrated up to 70 mg daily.

The dual primary outcomes were changes in the ADHD Rating Scale and the Barkley Sluggish Cognitive Tempo Scale. In the first treatment block, lisdexamfetamine had a medium effect size (0.68) for SCT, but the stimulant had only a nonsignificant effect during the second block, possibly due to a carryover effect. When the subjects on lisdexamfetamine were switched to placebo for the second block, their average ratings for SCT did not revert to baseline, suggesting that lisdexamfetamine’s benefits may have carried over after the switch. Alternatively, the findings in the first block may have been a false positive.

Unlike the changes in SCT, subjects’ ADHD ratings showed improvements in both four-week treatment periods with lisdexamfetamine (all p = <0.05), including measures of executive functioning and functional impairment.

Side effects were what we would expect from lisdexamfetamine: decreased appetite (11%), headache (10%), and anxiety (4%). There were no serious adverse events, and only one participant withdrew due to side effects (anxiety).

CARLAT TAKE

Patients with SCT and ADHD can expect to see improvement with amphetamine-based stimulants like lisdexamfetamine. SCT by itself is not an accepted diagnosis, and we should take caution to avoid overdiagnosis.