Immediate Impact

A prior exploratory study of 60 adults with attention-deficit/hyperactivity disorder (ADHD) has demonstrated improvements in ADHD symptoms with solriamfetol. According to Surman et al, “Compared to individuals on placebo, by study endpoint, a greater proportion of individuals in the treatment group met the prior-defined treatment response (CGI score indicating much or very much improved and AISRS score reduced ≥ 25%: 45% vs 6.9%, P = .0020). Those treated with solriamfetol also had greater improvement in total AISRS scores by week 3 through week 6 (P = .0012; week 6 effect size = 1.09).”​

On March 25, 2025, Axsome issued a press release for the FOCUS phase 3 trial of solriamfetol in the treatment of ADHD. Solriamfetol achieved its primary and key secondary endpoints, demonstrating statistically significant improvements in ADHD symptoms and disease severity compared to placebo. The FOCUS study was a randomized, double-blind, placebo-controlled, multicenter, US trial in which 516 adults with ADHD received solriamfetol 150 mg, solriamfetol 300 mg, or placebo once daily for 6 weeks. 

1. Surman CBH, Walsh DM, Horick N, DiSalvo M, Vater CH, Kaufman D. Solriamfetol for attention-deficit/hyperactivity disorder in adults: a double-blind placebo-controlled pilot study. Clin Psychiatry. 2023;84(6). doi:10.4088/JCP.23m14934

The FOCUS trial showed a statistically significant reduction in the Adult ADHD Investigator Symptom Rating Scale (AISRS) total score with solriamfetol compared to placebo at week 6. Solriamfetol 150 mg resulted in a mean reduction from baseline of 17.7 points, with placebo leading to a 14.3-point reduction (p=0.039). Overall, solriamfetol showed a 45% mean reduction from baseline in ADHD symptoms at week 6. Improvements in the AISRS total score were greater in patients treated with solriamfetol compared to placebo starting at week 1 (p=0.036). A statistically significantly greater percentage of patients treated with solriamfetol 150 mg (53.5%) achieved clinical response, a ≥30% improvement from baseline in the AISRS total score, compared to those treated with placebo (41.3%) at week 6 (p=0.024).

FOCUS also achieved its key secondary endpoint by statistically significantly reducing overall ADHD disease severity compared to placebo, as assessed by the Clinical Global Impression of Severity (CGI-S) for ADHD at week 6 (p=0.017). Results on the primary and key secondary endpoints for the exploratory 300 mg solriamfetol dose were numerically superior compared to placebo but were not statistically significant.​

This represents the first nonstimulant adult ADHD trial to show significant improvement at week 1 with a potential novel C4 medication option. For comparison, Viloxazine ER took 2 weeks to achieve symptomatic improvement and improved ADHD symptoms by 15 points at week 6, as compared to 17.7 points with solriamfetol. ​

Dr Jain –

Importance to Science: 6 
Importance to the Molecule: 8 
Importance to the Medication Class: 7 

This is good news, and it is impressive that one arm of the study separated from placebo, which is not all that easy to do. On the other hand, the failure of the 300 mg arm to separate from placebo is a very significant ding against this drug. Additionally, the magnitude of change appears not to be particularly impressive. So, while this is a positive movement in the right direction, it's going to be difficult to place this medication in the minds of clinicians. They will be wondering, “This is neither a stimulant nor a nonstimulant. Where do I use it?” So, it might end up being a niche medication and not have wide acceptability in psychiatry. 

Dr Cutler –

Importance to Science: 9
Importance to the Molecule: 10
Importance to the Medication Class: 9

This is a very big deal. The holy grail of ADHD treatment is having more effective nonstimulants, and this study is very significant as solriamfetol is a nonstimulant medication with a novel mechanism of action (MOA), high-affinity dopamine-norepinephrine reuptake inhibitor (DNRI) with 5-HT1A and TAAR1 agonism. This predicts efficacy for ADHD and depression, one of the most common comorbidities with ADHD. The efficacy seen at week 1 is a big plus, as is the overall drop in AISRS score of 17.7 points for the 150 mg dose. This is one of the fastest and biggest drops in ADHD ratings ever seen for a nonstimulant.

Dr Sohl –

Importance to Science: 8
Importance to the Molecule: 9
Importance to the Medication Class: 9

Dr Melmed –

Importance to Science: 6
Importance to the Molecule: 7
Importance to the Medication Class: 7

Scientific rigor is fair, with only moderately impressive results being evident, especially in comparison to those seen in stimulant medications. Understanding the MOA of antihypnotic medications on ADHD is an area definitely requiring further elucidation. The impact of sleep on ADHD symptoms will be used by clinicians in their rationale for choosing this option and in their discussions with patients. As a schedule IV, the attractiveness to an adult population is there (eg, cardiovascular issues, drug abuse, etc). Adverse events are not reported, hopefully no rashes, etc. A spate of trials in the use of antinarcolepsy and daytime sleepiness medications in the treatment of ADHD can be expected. 

Dr Mattingly –

Importance to Science: 7
Importance to the Molecule: 8
Importance to the Medication Class: 8

As a phase 3 trial result, this confirms the efficacy of solriamfetol for adult ADHD, which was seen in the phase 2 study by Surman et al. The study was well run. It was a 3-arm, placebo-controlled double study that evaluated 2 fixed doses of Sunosi vs placebo.

While the 300 mg arm was numerically greater than placebo, the 150 mg arm separated at week 1 and throughout the study. This would represent the first nonstimulant to significantly improve adult ADHD symptoms at week 1. The overall improvement of > 17 points on the ADHD rating scale is also approximately 2 points higher than what was seen in the adult phase 3 viloxazine ADHD trial.

Further studies need to be done to replicate these findings and to establish if there is a dose effect. As a current C4 scheduled medication, this could represent the first nonstimulant with fast onset for the improvement of adult ADHD symptoms.