Researchers performed a double-blind, placebo-controlled pilot study of solriamfetol.
“Ms Breanna” is a 47-year-old Caucasian female with a history of attention-deficit hyperactivity disorder (ADHD), diagnosed in adulthood. Her primary symptoms are inattention and impaired concentration. She has failed previous trials of amphetamine salts, atomoxetine, and guanfacine. She was unable to tolerate bupropion. She is currently taking extended-release methylphenidate with partial response/residual symptoms.
At her most recent outpatient visit, she reports that she has a brother with narcolepsy who takes solriamfetol. She inquires whether this medication could be of benefit to her ADHD. As her psychiatrist, how would you respond?
ADHD affects 2.5% to 4.4% of adults.1,2 Some patients have issues with tolerance to or effectiveness of approved agents, including residual symptoms. Solriamfetol, which is approved by the US Food & Drug Administration (FDA) for excessive daytime sleepiness in patients with narcolepsy or obstructive sleep apnea,3 is a dopamine and norepinephrine reuptake inhibitor with sympathomimetic properties. Therefore, this agent has potential clinical utility in the treatment of ADHD.
The Current Study
Surman and colleagues4 conducted a 6-week double-blind placebo-controlled, virtual visit-based pilot study of solriamfetol in 60 adults with ADHD. Using FDA-approved doses for sleep indications, the investigators hypothesized that solriamfetol would be well-tolerated and associated with reduced scores on the Adult ADHD Investigator Symptom Rating Scale (AISRS). Secondary outcomes were a higher rate of clinical improvement (25% reduction in ADHD symptoms and a Clinical Global Impression [CGI] scale rating of much or very much improved).
The investigators included individuals aged 18 to 65 years and conducted the trial between August 2021 and January 2023. Participants met DSM-5 criteria for ADHD and had an AISRS score of at least 20. Exclusion criteria were solriamfetol intolerance, conditions that obscured determination of an ADHD diagnosis, renal disease, pregnancy or nursing, unwillingness to use a reliable contraceptive method, cancer in the last 5 years, unstable medical illness, and conditions that could potentially be exacerbated by a sympathomimetic agent.
Participants were randomized to solriamfetol 75 mg or placebo in a double-blind fashion and had weekly visits for 6 weeks. Solriamfetol dose could be adjusted between 1 and 2 capsules based on tolerability, efficacy, and any adverse experiences, with the goal of stable dosing for the last 4 weeks of the study. Weekly assessments included the AISRS, the CGI, the Global Assessment of Functioning (GAF) scale, and spontaneous adverse experience reports. Participants also completed a number of self-ratings at baseline and endpoint.
AISRS total score at each visit was analyzed using linear mixed-effects regression models. Fisher’s exact test was used to evaluate proportions of patients based on improvement in AISRS scores, AISRS and CGI scores, adverse event patterns, and sleep measures.
Approximately 29 participants were randomized to solriamfetol, 100% of whom completed the study, and 31 participants were randomized to placebo, 29 of whom completed the study. Participants randomized to placebo were more likely to be Caucasian and women, and to have higher education and income. The mean participant age was 36 years, 45% of participants were male, 73% were Caucasian, and the mean AISRS score was 25. The majority of participants had moderate illness severity based on the CGI.
There were no significant differences in changes in vital signs between treatment groups. All adverse events were mild or moderate, except for 1 syncopal episode in the placebo group, and there were no significant differences between treatment groups. The most common adverse effects in the solriamfetol group relative to the placebo group were decreased appetite, headache, nausea/vomiting/diarrhea, and insomnia.
The mean improvement in AISRS total score was significantly greater for the solriamfetol vs the placebo group by week 6 (-7.2 vs -2.1, effect size=1.1). Patterns were similar for the AISRS inattentive and impulsive-hyperactive subscales. The total AISRS score improved 50% by week 6 in 28% in the solriamfetol group vs 3% in the placebo group. These findings were not moderated by changes in sleepiness scores (as measured by the Epworth Sleepiness Scale).
Significantly more participants in the solriamfetol groups self-reported improvements in executive functioning. There were no significant differences between participant groups on Pittsburgh Sleep Quality Index scale scores.
The investigators reported the first clinical trial of solriamfetol in adults with ADHD. They found that solriamfetol was well-tolerated and associated with significantly greater improvement in ADHD symptoms, with a large effect size, and participant self-report of executive function. Adverse effects were typical of FDA guidance for solriamfetol and other sympathomimetics used for ADHD.
Unique study strengths included the remotely conducted psychopharmacology trial design. Study attrition as well as the placebo response were noted to be very low. Potential study limitations included that more women than men were randomized to solriamfetol, and at-home blood pressure monitoring was used.
The Bottom Line
The findings suggest potential efficacy and tolerability of solriamfetol in adults with ADHD. Replication in future trials is clearly warranted. The present study also demonstrated the feasibility of an all-remote clinical trial.
Dr Miller is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times®. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.
1. Simon V, Czobor P, Bálint S, et al. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry. 2009;194(3):204-211.
2. Polanczyk G, de Lima MS, Horta BL, et al. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007;164(6):942-948.
3. Sunosi (solriamfetol) [package insert]. New York: NAT, Inc; June 2022.
4. Surman CBH, Walsh DM, Horick N, et al. Solriamfetol for attention-deficit/hyperactivity disorder in adults: a double-blind placebo-controlled pilot study. J Clin Psychiatry. 2023;84(6):23m14934.