Clinical Summary: Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study
Many adults with attention-deficit/hyperactivity disorder still have meaningful symptoms or executive dysfunction despite available medications, and some cannot tolerate standard options. This pilot trial tests whether solriamfetol, a dopamine and norepinephrine reuptake inhibitor already approved for sleepiness disorders, can provide a clinically useful alternative for adult ADHD.
Key Findings
- By week 6, the mean total improvement in AISRS score was −7.6 for active study drug participants and −2.1 for individuals on placebo (P = .0012; effect size = 1.09); the between-group mean AISRS difference at week 6 was −4.3 (95% CI, −7.7 to −1.0; P = .0106).
- Clinician-rated benefit separated from placebo by week 3, when the difference in mean AISRS scores was −3.4 (95% CI, −6.7 to −0.1; P = .0439), and remained significant through week 6.
- Response outcomes favored solriamfetol: total AISRS score improved 25% by week 6 in 52% of individuals on solriamfetol treatment versus 17% of individuals on placebo (P = .0119), and the prespecified responder definition occurred in 45% of participants in the treatment group and 6.9% in the placebo group (P = .0020).
- Symptom remission and global improvement were more common with solriamfetol: AISRS total score ≤ 18 occurred in 59% of participants on solriamfetol treatment and 21% on placebo (P = .0067), while CGI ratings of much or very much improved occurred in 45%, 13/29, versus 6%, 2/31 (P = .0020).
- Executive function and self-reported symptoms also improved more with active treatment: 69% versus 34% had a 0.5–standard deviation improvement on the BRIEF-A Global Executive Composite (P = .0173), and MASRS total scores changed by −11.1 (95% CI, −14.6 to −7.7) versus −3.9 (95% CI, −7.4 to −0.5; P = .0047; effect size = 1.23).
Solriamfetol 75 mg to 150 mg produced clinically meaningful improvement in adult ADHD symptoms, global status, and executive function over 6 weeks, with no significant excess cardiovascular signal versus placebo in this pilot trial. For adults who have not done well with standard ADHD treatments, solriamfetol is a credible off-label option that warrants serious consideration while larger confirmatory studies are awaited.
Practice Implications
- Consider solriamfetol for adults with attention-deficit/hyperactivity disorder who have inadequate benefit, partial benefit, or poor tolerability with approved ADHD medications, especially when inattention and executive dysfunction are prominent.
- Monitor blood pressure and heart rate during treatment, but note that in this 6-week trial there were no significant between-group differences in change in heart rate (+3.7 versus +2.2 bpm; P = .5609), systolic blood pressure (+2.4 versus +1.5 mm Hg; P = .6474), or diastolic blood pressure (+1.1 versus +1.5 mm Hg; P = .8117).
- Discuss appetite reduction, headache, gastrointestinal symptoms, insomnia, increased energy, cardiovascular symptoms, and neurologic symptoms as expected tolerability issues; adverse events led to dose adjustment or interruption in 10 subjects on active treatment and 4 on placebo.
- Do not assume ADHD improvement is simply a wakefulness effect: ESS scores improved by −2.4 points (P = .0056), but AISRS improvement was not moderated by changes in ESS ratings of sleepiness (P = .3735), and PSQI outcomes did not differ significantly between groups.
