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Article title: Solriamfetol improves daily fatigue symptoms in adults with myalgic
encephalomyelitis/chronic fatigue syndrome after eight weeks of treatment
Authors: Joel L. Young,1,2,4 Richard N. Powell*,2 Anna Powell,2 Lisa L. M. Welling,3 Lauren
Granata*,2 Jaime Saal1,2
*Corresponding Author
Lauren Granata: granata.lauren@gmail.com
Richard N. Powell: rpowell@rcbm.net; 441 South Livernois Suite 100, Rochester Hills, MI 48308
Affiliations: 1Rochester Center for Behavioral Medicine, Rochester Hills, MI, USA; 2MedaData,
LLC, Rochester Hills, MI, USA; 3Department of Psychology, Oakland University, Rochester, MI,
USA; 4School of Medicine - Wayne State University, Detroit, MI, USA
Clinical trial number: NCT04622293
Keywords: chronic fatigue syndrome, myalgic encephalomyelitis, wakefulness, solriamfetol
Acknowledgments
The authors would like to thank the participants in this study and the staff at RCBM for
supporting this trial.
Disclosures
The authors disclose the receipt of financial support for the research and publication of this
manuscript from Axsome Therapeutics.
Ethics approval and consent to participate
All methods were performed in accordance with the ethical standards laid down in the 1964
Declaration of Helsinki and its later amendments. All participants involved in this study provided
informed consent and gave permission for their de-identified data to be used in undisclosed
future research prior to their participation, and secondary research use of their information was
deemed ethical by the responsible IRB.
Consent for publication
Patients gave written consent for data publication.
Authors’ contributions
J.Y., J.S., and R.P. conceptualized the study. R.P., A.P., L.G., and L.W. designed and
performed statistical analyses and acquired regulatory approval. L.G. wrote the initial draft and
edited the manuscript. All authors reviewed and edited the manuscript.
Abstract
Background
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term illness with no
treatment options that address the disease directly. Solriamfetol is a selective dual
norepinephrine-dopamine reuptake inhibitor that promotes wakefulness in obstructive sleep
apnea and narcolepsy.
Aims
This study evaluated the efficacy and safety of solriamfetol for fatigue symptoms in adults with
ME/CFS with 8 weeks of treatment.
Methods
This was a phase 4, double-blind, randomized, placebo-controlled trial of solriamfetol in adults
with ME/CFS. Eligible participants were randomly assigned to receive 75mg (titrated to 150mg
as needed) solriamfetol or placebo. Participants completed a battery of assessments at weekly
visits. The primary outcome was Fatigue Symptom Inventory (FSI) scores, and the secondary
outcome measure was Behavioral Rating Inventory of Executive Function for Adults (BRIEF-A),
at weeks 6 and 8. T-tests assessed the differences in mean change from baseline between
solriamfetol and placebo. Adverse events were monitored throughout the study.
Results
At week 8 (p = .039), but not week 6 (p = .270), solriamfetol improved FSI severity compared to
placebo. On the BRIEF-A global executive composite, solriamfetol improved more than placebo
at week 8 (p = .012), driven by improved metacognition index (p = .004), but not behavioral
regulation index (p = .574). Solriamfetol was well tolerated, with most common AEs being sleep
loss and headaches.
Conclusions
Solriamfetol demonstrated good safety and efficacy in improving fatigue and executive
functioning in patients with ME/CFS. As a dual norepinephrine-dopamine reuptake inhibitor and
wakefulness-promotion, solriamfetol has the potential to improve fatigue symptoms of ME/CFS.
Introduction
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness of
unknown etiology involving complex dysregulation of the central nervous, immune, and
endocrine systems.[1–3] ME/CFS is characterized by the primary symptom of chronic fatigue. The
rapid and sustained fatigability in response to low-level physical and mental exertion
distinguishes ME/CFS from fatigue experienced from other conditions, particularly with the low
threshold of onset and prolonged recovery unique to ME/CFS.[2,3] The unexplained fatigue may
be accompanied by impaired neurological, immune, gastrointestinal, urogenital, cardiovascular,
and autonomic functioning.[1,2] ME/CFS is a long-term illness that ubiquitously affects all racial,
ethnic, and socioeconomic groups.[3] Its prognosis is generally considered poor, with reported
recovery rates of 0-8% and improvement rates ranging between 17% and 64%.[4]
ME/CFS is commonly found after infection, but there is no clearly defined
pathophysiology.[3] Prevailing hypotheses suggest the involvement of neuroinflammation
affecting the central nervous system and peripheral processes as underlying factors in disease
onset.[3,5] Several mechanisms leading to dysregulation have been implicated and supported by
observational patient studies,[6–9] including an interplay between inflammatory pathways,[9]
overactivated glial cells,[10] altered serotonin transmission,[11,12] and neuroendocrine
dysfunction.[13,14] Without a definitive underlying mechanism, there are currently no medications
specifically indicated for ME/CFS approved by the United States Food and Drug Administration
(U.S. FDA) that address the disease directly. Instead, treatment plans include pharmacologic
interventions that attempt to alleviate symptoms like depression, orthostatic intolerance, and
pain, or to address perpetuating factors. These include mild pain relievers, COX-2 inhibitors,
non-steroidal anti-inflammatory drugs, antidepressants, and immune modulators.[15–17] Non-
pharmacologic treatments, like graded exercise and cognitive behavior therapy, may be
beneficial for some patients, but evaluations yield inconsistent results.[17]
The purported role of serotonin in the pathophysiology of ME/CFS has led to the
investigation of selective serotonin reuptake inhibitors (SSRIs) to treat cognitive symptoms,
fatigue, and secondary symptoms related to mood, activity, and sleep.[15,18] Although some
antidepressant trials, including those of venlafaxine and escitalopram, have demonstrated
improvement in fatigue and depressive symptoms,[19,20] there is insufficient evidence that
serotonergic medications are a reliable treatment option for ME/CFS.[21,22] Initial investigations of
drugs that modulate either dopamine or norepinephrine, such as modafinil or selegiline, have
shown promise for alleviating secondary symptoms, but no consistent effect on fatigue has been
found.[23,24] Recent studies have more strongly supported the possibility that dual inhibitors of
dopamine and norepinephrine may be more effective in treating fatigue.[25,26] For example,
bupropion, a norepinephrine and dopamine reuptake inhibitor (NDRI), improved fatigue and
sleepiness symptoms in a large clinical population with major depressive disorder more
effectively than a comparator SSRI and placebo.[27] Similarly, CNS stimulants considered to be
NDRIs, including methylphenidate, dextroamphetamine, and lisdexamfetamine, relieve fatigue
and cognitive symptoms in some patients.[28–31]
Solriamfetol (formerly known as JZP-110 and ADX0N006) is a selective NDRI indicated
to promote wakefulness in obstructive sleep apnea and narcolepsy.[32] Solriamfetol has a lower
binding affinity to dopamine and norepinephrine transporters than other stimulants and does not
promote the release of monoamines, as amphetamine stimulants do.[33,34] In previous trials for
obstructive sleep apnea and excessive daytime sleepiness in adults, solriamfetol improved
wakefulness, reduced sleepiness, and improved patient ratings on the Patient Global
Impression of Change Scale compared to placebo. These effects extended to improvements in
daily functioning, health-related quality of life, and work productivity over 12 weeks of
treatment.[34,35] Solriamfetol would be a preferable treatment option compared to many of the
stimulants proposed to treat ME/CFS because of its milder side effect profile and lower risk of
abuse and dependence.[36] Due to its mechanism of action as a dual reuptake inhibitor of
dopamine and norepinephrine and the symptom improvement documented in patients with
excessive daytime sleepiness, the present study evaluates the efficacy of solriamfetol in treating
fatigue symptoms in adults with ME/CFS.
Methods
Study Design and Oversight
This phase 4, double-blind, randomized, placebo-controlled, single-center trial was
reviewed and approved by the WCG Institutional Review Board and registered under
ClinicalTrials.gov identification number NCT04622293.
Participants
Participants were adults aged 18-65 years at the time of consent who met the Institute of
Medicine (IOM) 2015 diagnostic criteria for ME/CFS. Sexually active participants agreed to
practice two different methods of contraception or remain abstinent during the trial and for 30
days after the end of the study. Women had to test negative for pregnancy, and all participants
had to pass a drug screen for substances that are illegal for recreational use in Michigan at the
screening visit (visit 1). Participants must have had a minimum level of intellectual functioning as
determined by the investigator, no history of intellectual impairment or a severe learning
disability, be fluent in English, and score at least 4 on the Clinical Global Impression Scale-
Severity (CGI-S)[37] at visit 1.
Treatment
All participants provided written informed consent before any study procedures began.
Eligibility was assessed at visit 1, where vital signs, urine pregnancy and drug screens, and
psychometric assessments, including the Behavioral Rating Inventory of Executive Function for
Adults (BRIEF-A),[38] CGI-S,[37] CGI-Improvement (CGI-I),[37] Patient Global Impression-Severity
(PGI-S),[39] Patient Global Impression-Improvement (PGI-I),[39] Fibromyalgia Impact
Questionnaire (FIQ),[40] Fatigue Symptom Inventory (FSI),[41] Mini-International Neuropsychiatric
Interview (MINI),[42] and Columbia-Suicide Severity Rating Scale (C-SSRS)[43] were completed.
At visit 2 (baseline), eligible patients were randomly assigned to solriamfetol or placebo. Jazz
Pharmaceuticals, Inc. provided solriamfetol capsules and placebo tablets in matching capsules.
Participants and researchers were blinded to treatment allocation throughout the study period.
All participants started the study with 75mg solriamfetol (1 capsule) or matching placebo. They
were instructed to take 1 whole capsule at the same time each morning upon waking, with or
without food. Dose titration began on day 3 of the study, where solriamfetal could be titrated to
150mg as needed. The dose titration schedule is described in Supplementary Table 1.
Solriamfetol could be safely discontinued without taper or titration at any time.
All participants completed baseline, week 3, and week 8 visits in person, while other
weekly visits could be completed in person or with a primary investigator via a telehealth
platform. Participants conducting telehealth visits were asked to take their own blood pressure
and heart pulse rate, when possible, and completed study assessments with the investigator.
Participants completed the eligibility screening, 8 weeks of double-blind treatment, and a post-
treatment follow-up 1 week after the week 8 visit.
Outcome measures
The primary outcome was the FSI[41] score at weeks 6 and 8. The FSI is a 13-item
fatigue self-report scale with excellent internal reliability and good convergent and construct
validity.[44] The four Severity subscale items ask respondents to rate their fatigue from 0 (“Not at
all fatigued”) to 10 (“As fatigued as I could be”) on their most fatigued day during the past week,
least fatigued day during the past week, average level of fatigue during the past week, and
current fatigue. The seven Interference subscale items assess how much the fatigue interferes
with the respondent’s activities of daily living, concentration, relationships, enjoyment of life, and
mood from 0 (“No interference”) to 10 (“Extreme interference”). The last two questions assess
the duration and frequency of the fatigue the respondent experiences.
The secondary outcome was the BRIEF-A[38] at weeks 6 and 8.[38] The BRIEF-A is a 75-
item, 9-scale, self-report measure that assesses inhibition, self-monitoring,
planning/organization, shifting, initiation, task monitoring, emotional control, working memory,
and organization of materials. The BRIEF-A results in a Global Executive Composite (GEC)
score composed of the Metacognition Index (MI) (from the Initiation, Working Memory,
Planning/Organization, Organization of Materials, and Task Monitoring subscales) and Behavior
Regulation Index (BRI) (from the Inhibition, Shifting, and Emotional Control) subscales.[45]
Exploratory outcome measures included the PGI-S, PGI-I,[39] CGI-S, CGI-I,[37] FIQ,[40]
and Sheehan Disability Scale (SDS).[46] PGI-S and PGI-I are single item, six-point, self-rated
scales to assess health severity and perceived change after receiving a particular therapy or
treatment.[39,47,48] The CGI-S rates illness severity on a 7-point scale from 1 (“normal”) to 7
(“extremely ill”), and the CGI-I rates improvement on a 7-point scale from 1 (“very much
improved”) to 7 (“very much worse”) since the initiation of treatment.[37] CGI-S and CGI-I have
good validity and have proven useful in evaluating a variety of mental health conditions.[49–52]
The FIQ is a 20-item assessment with questions pertaining to severity across three domains:
physical function, overall impact, and symptoms. It has been one of the most frequently used
assessment tools for fibromyalgia since its development in 1991.[40] The SDS is a three-item tool
to measure functional disability in work, family, and social life, originally designed for use in
psychiatry. Each item assesses how much symptoms disrupt work, family, or social life from 0
(“not at all”) to 10 (“extremely”). The SDS has been shown to be sensitive to treatment effects,
with strong internal consistency and construct validity for identifying patients with functional
impairment.[46,53]
Safety and tolerability were assessed from the time of consent through the follow-up visit
taking place one week after the week 8 visit. A series of vitals, including blood pressure and
pulse rate, were collected at every visit.
Statistical Analysis
Before the trial, the sample size was determined with a power analysis using a two-sided
variance test by effect size (Cohen’s d). Assuming a population effect size is 1.0, a minimum
sample size of 34 total participants would be required to reject a null hypothesis of zero at a
significance level of p < .05. Similar effect sizes are found for solriamfetol when compared to
placebo for differences in wakefulness-promotion.[54] Outcomes were tested using t-tests to
assess the difference between placebo and solriamfetol groups in the mean change from
baseline for FSI and BRIEF-A subscales at week 8. Analyses utilized an intent to treat model
and a significance level of p < .05.
Results
Participant demographics and disposition
A total of 47 participants were screened. Nine participants did not meet screening
requirements due to having a current comorbid uncontrolled psychiatric disorder (n = 4) and/or a
serious chronic or acute unstable medical condition or illness (n = 7) and were excluded from
the study. Three participants withdrew from the study after passing the screening visit, but
before the baseline visit and before receiving treatment. The final sample consisted of 38
participants (demographic characteristics are summarized in Table 1). Of these, 18 received at
least one dose of solriamfetol and 20 received placebo. Two participants in the placebo group
and one in the solriamfetol group withdrew from the study due to on-label adverse events (AEs).
One participant in the solriamfetol group withdrew due to travel requirements.
Table 1. Participant demographics
Treatment
SOL
PLA
Total enrolled, n
18
20
Age, y, mean (range)
41.30 (20 - 64)
39.11 (18 - 62)
Gender, n (%)
Male
5 (26.3%)
3 (15.0%)
Female
13 (73.7%)
17 (85.0%)
Nonbinary
0 (0%)
0 (0%)
Race, n (%)
White/Caucasian
17
18
Black/African American
1
1
Asian
0
0
Other
0
1
PLA, placebo; SOL, solriamfetol.
Baseline characteristics
At the baseline visit, participants in the solriamfetol and placebo groups did not differ in
any of the measured assessments (Table 2).
Primary and secondary endpoints
The study met its primary endpoint of change from baseline in the severity subscale of
the FSI at week 8, but not at week 6. At week 8, participants assigned solriamfetol exhibited a
2.02-point improvement compared to the 0.46-point improvement in the placebo group (p
= .039) (Table 3, Figure 1). The secondary outcome of BRIEF-A change from baseline was
analyzed by its three subscales, GEC, MI, and BRI. For the GEC scale, patients assigned
solriamfetol showed a greater improvement compared to placebo at week 8, and for the MI
scale, the solriamfetol group had greater improvements as early as week 6 (Table 3, Figures 2-
3). There were no statistically significant differences between the solriamfetol- and placebo-
assigned participants in the BRI subscale or the exploratory measures of CGI and FIQ change
from baseline at weeks 6 or 8. There was an improvement with solriamfetol compared to
placebo in the PGI-S scale at weeks 6 and 8 (Figure 4). The Sheehan Disability Scale was not
analyzable due to lack of subject responses from week 8.
Table 2. Baseline characteristics
SOL
PLA
Assessment
n
(mean ± SD)
n
(mean ± SD)
FSI: Severity
18
6.57 (1.55)
20
7.14 (1.55)
FSI: Interference
18
6.56 (1.78)
20
6.90 (1.72)
BRIEF-A: GEC
16
16.20 (2.99)
20
16.79 (3.38)
BRIEF-A: MI
16
9.85 (2.10)
20
9.42 (1.74)
BRIEF-A: BRI
16
6.95 (1.50)
20
6.78 (1.50)
PGI-S
18
3.28 (0.67)
19
3.11 (0.94)
CGI-S
18
4.56 (0.70)
17
5.06 (0.75)
FIQ
18
69.83 (17.76)
20
69.50 (15.98)
BRI,behavioral regulation index; BRIEF-A, Behavioral Rating Inventory of Executive
Function for Adults; CGI-S, Clinical Global Impression-Severity; FSI, Fatigue Symptom
Inventory; GEC, global executive composite; MI, metacognition index; PGI-S, patient global
impression - severity; PLA, placebo; SOL, solriamfetol.
Safety outcomes
In total, 14 (36.8%) patients randomized to receive solriamfetol or placebo reported at
least one AE. Two participants in the placebo group withdrew due to AEs; both reported sleep
loss and one also experienced headaches, dizziness, and anxiety. Remaining patients who
received solriamfetol and placebo reported a total of 13 and 16 AEs, respectively (Table 4). The
most common AE reported in patients who received solriamfetol was sleep loss (6 instances, 3
patients), whereas the AE experienced by the greatest number of patients in this group was
anxiety (4 instances, 4 patients). In contrast, the most common AE reported in patients who
received placebo was headaches (8 instances, 4 patients), which was also the AE experienced
by the greatest number of patients in this group. There were no new safety signals reported.
Table 3. Test of FSI and BRIEF-A subscales and exploratory endpoints, PGI, CGI, and FIQ at weeks 6 and 8.
Week 6
Week 8
n
n
Assessment
SOL
PLA
Difference
from Placebo
(95% CI)
p
Cohen’s d
SOL
PLA
Difference
from Placebo
(95% CI)
p
Cohen’s d
FSI: Severity
15
14
-0.74
(-2.18, 0.60)
.270
0.42
15
17
-1.42
(-2.78, -0.05)
.042
0.75
FSI:
Interference
15
14
-0.67
(-2.13, 0.79)
.353
0.35
15
17
-1.11
(-2.59, 0.38)
.138
0.54
BRIEF-A:
GEC
16
17
-1.62
(-3.33, 0.097)
.064
0.67
14
16
-2.13
( -3.76, 0.51)
.012
0.99
BRIEF-A: MI
16
17
-1.24
(-2.27, -0.22)
.019
0.86
14
16
-1.56
( -2.57, -0.54)
.004
1.15
BRIEF-A: BRI
16
17
-.38
(-0.41, 1.16)
.334
0.34
14
16
-.57
(-1.35, .20)
.574
0.56
PGI-S
15
14
-0.88
(0.14, 1,63)
.022
0.90
15
17
-.73
(-1.44, .02)
.043
0.75
CGI-S
16
15
-.08
(0.84, 0.69)
.834
0.08
15
13
.14
(-1.16, 0.87)
.773
-0.11
FIQ
15
14
-8.71
(-21.38, -3.95)
.169
0.52
15
16
-10.39
(-22.67, 1.90)
.169
0.62
BRI, Behavior Regulation Index; BRIEF-A; Behavioral Rating Inventory of Executive Function for Adults; CGI-S, Clinical
Global Impression-Severity; FIQ, Fibromyalgia Impact Questionnaire; FSI, Fatigue Symptom Inventory; GEC, Global
Executive Composite; MI, Metacognition Index; PGI-S, Patient Global Impression-Severity; PLA, placebo; SOL,
solriamfetol.
Table 4. Participants who experienced AEs during the study.
Treatment
Participants with AEs, n (%)
SOL
(n = 18)
PLA
(n = 20)
Total
8 (44.44)
6 (30.00)
Headaches
2 (11.11)
4 (20.00)e,f,g
Sleep loss
3 (16.67)a,b,c
3 (15.00)e,g
Dizziness
0
2 (10.00)e,f
Anxiety
4 (22.22)a,b,c
1 (5.00)e
Eye twitching
0
1 (5.00)
Chest pain
1 (5.56)d
0
Dry mouth
1 (5.56)d
0
AE, adverse event; PLA, placebo; SOL, solriamfetol.
Matching superscript letters represent one participant who experienced
multiple AEs.
Figure 1. Change from baseline of FSI: Severity, the primary outcome, in patients receiving
solriamfetol or placebo. Patients assigned to solriamfetol had significantly decreased FSI
severity compared to placebo at week 8.
Figure 2. Change from baseline of BRIEF-A: GEC scores, a secondary outcome, in patients
receiving solriamfetol or placebo. Patients assigned to solriamfetol had significantly decreased
BRIEF-A: GEC scores compared to placebo at week 8.
Figure 3. Change from baseline of BRIEF-A: Metacognition Index scores, a secondary
outcome, in patients receiving solriamfetol or placebo. Patients assigned to solriamfetol had
significantly decreased BRIEF-A: MI scores compared to placebo at weeks 6 and 8.
Figure 4. Change from baseline of PGI-S, an exploratory outcome, in patients receiving
solriamfetol or placebo. Patients assigned to solriamfetol had significantly decreased PGI-S
severity compared to placebo at weeks 6 and 8.
Discussion
Solriamfetol, titrated to an optimal dose of 75mg or 150mg depending on participants’
tolerance and response, led to significant improvements in fatigue symptoms and executive
function over an 8-week treatment period. In this double-blind, placebo-controlled trial,
participants demonstrated faster and more prominent improvements on the severity subscale of
the FSI and the BRIEF-A (GEC and MI) with solriamfetol compared with placebo. Solriamfetol
has a unique mechanism of action that has shown benefit for patients with sleep disorders, and
this trial demonstrates its potential to be an effective treatment for the fatigue and cognitive
symptoms associated with ME/CFS.
The FSI, the primary outcome measure, has been validated in previous studies with
heterogeneous patient populations across genders, age, and clinical diagnosis, including
cancers.[41,44] The scale allows for the measurement of the intensity and duration of fatigue, with
its questions pertaining to symptom severity and the degree to which the symptoms interfere
with the patients’ lives. Interestingly, patients did not experience improvements in the
interference subscale compared with placebo, although their symptom severity improved at
week 8. In other studies, FSI severity and interference subscales demonstrate strong internal
consistency reliability.[55] The discrepancy between the two measures could indicate delayed
recovery as an effect of cumulative fatigue.[56] If severity improves after 8 weeks of treatment,
cumulative impacts of long-term fatigue may continue to disrupt daily activities. Longer follow-up
would determine whether interference improves with more time on treatment.
At week 8, executive function improved with solriamfetol as measured by the BRIEF-A.
Global improvement in executive function was driven by the MI, which relates to planning,
organization, and memory. In contrast, the BRI, relating to inhibition, shifting, and emotional
control, was not affected by solriamfetol. Deficits in inhibition and behavioral shifting represent a
low degree of cognitive flexibility, which can make higher order reasoning and planning more
difficult.[57] Differences in efficacy between BRIEF-A subscales can contribute to characterizing
different types of fatigue and delineating the behaviors most impacted and most susceptible to
treatment. For example, when compared with ADHD rating scales, MI is more strongly
correlated with inattention, and BRI is more strongly correlated with impulsivity and
hyperactivity.[57] Therefore, understanding that solriamfetol primarily enhances executive
functioning related to metacognition may guide decisions regarding other interventions,
particularly when impulsivity and hyperactivity are affecting daily functioning.
The PGI-S was significantly improved with solriamfetol at weeks 6 and 8, but CGI-S was
not affected by treatment. Although the CGI is widely used in psychiatry, clinician ratings in
certain settings may not fully capture the patient’s perspective on their impairment.[58] In a study
of patients being treated for multiple sclerosis, patients less frequently rated themselves as
unchanged compared to their physicians, who were less likely to report improvement.[59] In the
case of ME/CFS, physicians may be less likely to change their severity rating if distress and
impairment are still present, even when patients experience reduced fatigue. Discordance
between patient- and clinician-reported severity can be a barrier to effective treatment, so
patient and clinician alignment is paramount in order to ensure treatment plans are meeting the
patient’s needs.[60]
FIQ scores were not impacted by solriamfetol at any time point. The scale was included
as an exploratory measure because there is broad overlap between ME/CFS symptoms and
fibromyalgia symptoms.[21,61] However, the FIQ includes questions related to physical
functioning, work difficulties, pain, fatigue, morning tiredness, stiffness, anxiety, and depression.
The wakefulness-promoting properties of solriamfetol may have the potential to subsequently
benefit pain and physical impairments measured by the FIQ. However, fibromyalgia and
ME/CFS are distinct disorders, and the FIQ may not be the most effective scale to measure the
cognitive fatigue experienced in ME/CFS.[21] Future research could explore more targeted
assessments of cognitive fatigue and its relationship to treatments like solriamfetol in ME/CFS
patients to better understand its potential impact.
The current study is limited by the small, homogenous sample. As a single-center study
with limited geographical reach and racial and gender diversity, these findings provide a
foundation on which a larger clinical trial should be conducted to corroborate the results.
Additionally, there was a large degree of variability in the baseline scores, although these were
controlled for by analyzing changes from baseline. Overall, future studies with larger, more
diverse populations will be crucial to further validate the current findings and improve
generalizability.
In this study, solriamfetol compared to placebo improved fatigue and cognitive
symptoms after 6 and 8 weeks of treatment in adult patients with ME/CFS. Specifically,
solriamfetol improved overall fatigue as measured by the FSI severity subscale and
metacognitive symptoms related to planning, organization, and memory components of
executive function measured by the BRIEF-A MI. Patients reported improvement in disease
severity, and treatment was well-tolerated. These findings support solriamfetol, with its
wakefulness-promoting characteristics, as a promising treatment for ME/CFS, a disease with no
currently-approved treatments.
Supplementary Table 1. Dose titration schedule.
Visit
1
2
3
4
5
6
7
8
Week
0
1 (Day 3)
2
3
4
6
8
Solriamfetol
dose
N/A
75 mg
75 mg or
150 mg
75 mg or
150 mg
75 mg or
150 mg
75 mg or
150 mg
75 mg or
150 mg
75 mg or
150 mg
Abbreviations
AE, adverse event
BRIEF-A, Behavioral Rating Inventory of Executive Function for Adults
BRI, behavioral regulation index
CFS, chronic fatigue syndrome
CGI-S, Clinical Global Impression-Severity
FIQ, Fibromyalgia Impact Questionnaire
FSI, Fatigue Symptom Inventory
GEC, global executive composite
ME, myalgic encephalitis
MI, metacognition index
PGI-Severity, Patient Global Impression-Severity
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