Attention-deficit/hyperactivity disorder (ADHD), long thought of as a childhood condition, is increasingly recognized as a disorder that can persist into adulthood.
Up to 60% of children with ADHD continue to experience symptoms as adults.
Yet treatment options specifically tested and approved for adult ADHD remain limited.
A new study published this month in the Journal of Clinical Psychiatry points to a promising potential new medication option for adults with ADHD.
Key facts:
- Researchers tested the medication solriamfetol in a 6-week randomized, double-blind, placebo-controlled trial with 60 adults who met DSM-5 criteria for ADHD.
- Compared to placebo, solriamfetol was associated with significantly greater improvement in ADHD symptoms as measured by the Adult ADHD Investigator Symptom Rating Scale (AISRS).
- 45% of participants treated with solriamfetol were considered “treatment responders” based on improved AISRS scores and clinician ratings, compared to only 6.9% of those receiving placebo.
- Solriamfetol was generally well-tolerated, with no significant effect on heart rate or blood pressure compared to placebo. The most common side effects were decreased appetite, headache, gastrointestinal issues, insomnia, increased energy, cardiovascular effects, and neurological effects.
Source: J Clin Psychiatry 2023
Current Treatment Limitations for Adults with ADHD
While medications like methylphenidate (Ritalin) and mixed amphetamine salts (Adderall) are FDA-approved and widely used for treating ADHD in children, fewer options have been formally tested and approved specifically for adults.
The recent approval of lisdexamfetamine (Vyvanse) in 2008 marked the first ADHD medication approved for adults, highlighting the previous lack of research on pharmacological treatments tailored to adult ADHD.
Current first-line medications for adults include stimulant medications like methylphenidate, amphetamines, and lisdexamfetamine.
However, these medications do not work for everyone.
Up to 30% of adults with ADHD don’t respond to or tolerate stimulants adequately.
Non-stimulants like atomoxetine (Strattera) offer an alternative, but also have limitations in efficacy and side effects.
Researchers have noted the pressing need for expanded treatment options that are rigorously studied for adults who struggle to achieve symptom control with available therapies.
Finding and testing potential new medications is crucial for improving care and outcomes.
Testing a Novel Compound: Solriamfetol (Sunosi)
To help address this research gap, a team led by Dr. Craig Surman at Massachusetts General Hospital conducted a randomized controlled trial examining a new molecular compound, solriamfetol, for treating ADHD in adults.
Solriamfetol is a selective norepinephrine and dopamine reuptake inhibitor (NDRI).
It inhibits the reuptake of dopamine and norepinephrine, which are neurotransmitters thought to play a key role in ADHD symptoms related to inattention and hyperactivity.
By keeping more dopamine and norepinephrine available in the brain, solriamfetol aims to improve signaling in neural pathways important for attention, focus, and impulse control.
While solriamfetol acts on similar neurotransmitter systems as stimulants used for ADHD, it is chemically distinct as a member of the phenylalanine class rather than the amphetamine class.
Researchers hoped this unique mechanism could offer robust efficacy with lower abuse potential and fewer adverse cardiovascular effects compared to amphetamine-based agents.
Double-Blind Placebo-Controlled Trial Design
To rigorously test solriamfetol’s efficacy and safety, the researchers conducted a randomized, double-blind, placebo-controlled trial, considered the gold standard for clinical studies.
Sixty adults with ADHD diagnosed using DSM-5 criteria were randomly assigned to receive either solriamfetol or placebo in identical pill form.
Neither participants nor researchers were aware of who received solriamfetol versus placebo during the study.
This double-blind design helps minimize potential bias in reporting symptoms or side effects.
Participants underwent a 6-week dose optimization phase, during which solriamfetol dosage could be adjusted between 75mg and 150mg daily based on clinical response and side effects.
This reflects how dosing would be individualized and titrated in real-world clinical practice.
Throughout the trial, participants and clinicians completed standardized scales evaluating ADHD symptoms, overall functioning, sleep, and side effects.
The primary outcome measure was the Adult ADHD Investigator Symptom Rating Scale (AISRS), scored by clinicians to evaluate severity of inattention and hyperactivity-impulsivity.
Significant Improvements in ADHD Symptoms with Minimal Side Effects
After 6 weeks of optimized treatment, the researchers found that solriamfetol led to significant improvement in ADHD symptoms compared to placebo, as measured by the AISRS.
- 45% of those who received solriamfetol met the definition of “treatment responders,” meaning they had at least a 25% reduction in AISRS score plus a clinician rating of “much improved” or “very much improved.”
- In contrast, only 6.9% of the placebo group were considered treatment responders by this definition.
- On the AISRS inattention and hyperactivity-impulsivity subscales, the solriamfetol group improved by 11.7 and 9.5 points respectively, compared to only 2.9 and 2.4 point improvements for the placebo group.
These findings suggest that for adults struggling with impairing ADHD symptoms not adequately controlled by other therapies, solriamfetol may provide substantial symptom relief and functional improvement.
The significance and robustness of the treatment effect provides promising evidence that solriamfetol could become an effective option in the adult ADHD medication arsenal.
Importantly, solriamfetol was also generally well tolerated without concerning side effects in this trial.
There was no significant difference in heart rate or blood pressure changes compared to the placebo group.
The most common side effects noted were decreased appetite, headache, gastrointestinal issues like nausea and diarrhea, insomnia, increased energy, some cardiovascular effects like chest pain, and some neurological effects like irritability.
Overall rates of both total and severe adverse events were similar between the solriamfetol and placebo groups.
The minimization of blood pressure changes and cardiovascular concerns is particularly notable, given that these are common and potentially serious side effects with stimulant medications like amphetamines.
The researchers suggest solriamfetol’s distinct mechanism of action may account for the relatively low rate of cardiovascular issues observed.
Wider Applications: Treating Sleepiness and Cognitive Impairment Too?
Beyond measuring core ADHD symptom improvement, the study also collected data on other facets of daily functioning, including sleep, cognitive performance, and global functioning.
The solriamfetol group showed greater improvement on the Epworth Sleepiness Scale, indicating reduced daytime sleepiness.
They also had slightly better scores on a scale of executive functioning related to attention, inhibitory control, working memory and other cognitive skills essential for managing life with ADHD.
The solriamfetol group additionally had higher ratings on the Global Assessment of Functioning scale, suggesting medication-linked enhancement of general wellbeing and ability to manage daily responsibilities.
These ancillary benefits raise intriguing possibilities that solriamfetol could potentially target sleepiness and cognitive dysfunction in ADHD – and even possibly cognitive disorders like Alzheimer’s disease – given its dual action on dopamine and norepinephrine systems implicated in alertness and executive function.
However, the researchers emphasize that further study is needed before extending applications beyond ADHD treatment.
The cognitive and sleep-related measures were secondary in this trial, and the differences between groups, while statistically significant, were relatively small in magnitude.
Ongoing Research Needed to Replicate and Extend These Findings
While highly promising, the authors caution that these results require replication in larger, longer-term trials before solriamfetol could be deemed an evidenced-based ADHD treatment.
Participants in this study had already exhibited inadequate response to previous standard medications, possibly accounting for the high responsiveness to a new agent.
It will be important to demonstrate similar efficacy for adults with ADHD who are treatment-naïve or well-managed on existing therapies.
Follow-up work should also include children with ADHD, as most medications are tested first in pediatric samples.
Understanding solriamfetol’s long-term maintenance of effect, optimal dosing, duration of action, misuse potential, and impacts on quality of life will also be critical next steps.
A Major Step Forward, but More Work Ahead
In summary, this rigorous placebo-controlled trial provides the first evidence that solriamfetol may represent a badly needed new treatment option for adults with ADHD who struggle with standard stimulant medications.
The magnitude of symptom improvement and tolerability demonstrated by solriamfetol are extremely encouraging.
At the same time, this study marks only the beginning of the extensive clinical research needed to fully establish solriamfetol as an evidence-based therapy.
If subsequent studies corroborate these findings over longer time periods and in larger samples, solriamfetol could fill an important gap in pharmacologic options for underserved adults with inadequately controlled ADHD.
But verification of efficacy, safety, and functional outcomes will be critical before this medication makes it into routine clinical use.
This trial’s success highlights the vital importance of developing and testing promising new compounds in robust placebo-controlled studies specifically tailored to adult ADHD.
As awareness and diagnoses of adult ADHD continue to rise, expanding the arsenal of medical therapies proven effective and safe for this population should be an urgent public health priority.
Solriamfetol likely represents just one of many yet-untapped opportunities to bring better treatments to the millions of adults living with ADHD.
References
- Study: Solriamfetol for ADHD in adults: a double-blind placebo-controlled pilot study
- Authors: Craig B. H. Surman MD et al. (2023)
