Trial Report Solriamfetol improves daily fatigue symptoms in adults with [ME/CFS] after 8 weeks of treatment, 2025, Young et al

I take Solriamfetol (brand name Sunosi in U.S.). It's comes in 75 MG and 150 MG. I split the lower dosage, so take 37.5 MG.

I don't find it energizing, but it acts as a subtle mood lift. For some reason, I also find it calming, but given how it works, I don't know why that is.
 
For me, stimulants are helpful in the way that a bank loan is helpful. Sometimes you need the resources to do something time sensitive. But it all has to be paid back eventually.

As other posters have said, this result is meaningless without long term follow up using objective activity measures. Otherwise patients could just be borrowing again to pay off yesterday’s loan, with the total owed mounting all the time. Eventually the bailiffs will come knocking.
 
Letter to the editor —

“Too small to succeed?” Rethinking efficacy claims in a solriamfetol trial for ME/CFS
Zhihao Lei

Web | DOI | PDF | Journal of Psychopharmacology | Paywall

First, the trial’s sample size and scope were very limited. Only 38 patients were enrolled, all from a single center. Such a small, single-site sample raises the risk of statistical error and limits generalizability. The power calculation assumed an extraordinarily large effect (Cohen’s d = 1.0), which is an optimistic estimate rarely achieved in practice …
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Second, the primary outcome results do not clearly support the authors’ claims of “strong” efficacy. Fatigue Symptom Inventory (FSI) scores did not differ significantly between solriamfetol and placebo at week 6 (p = 0.270), and showed only a marginal difference at the final week 8 endpoint (p = 0.039). The latter barely meets the conventional alpha threshold and would be non-significant if any adjustment for multiple looks or endpoints were applied …
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Third, the study employed multiple secondary endpoints and analyses without any apparent correction for multiplicity. In addition to the primary fatigue outcome, the authors assessed executive functioning via the Behavior Rating Inventory of Executive Function–Adult (BRIEF-A) and its subscales at two time points, among other measures. Conducting numerous significance tests inherently increases the chance of false-positive results …
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Fourth, the trial’s dose-escalation design complicates the interpretation of the results. All participants randomized to solriamfetol began at 75 mg, with the option to titrate to 150 mg after only 3  days based on need/tolerability. In practice, this meant most patients were likely receiving the highest dose (150 mg) early in the 8-week trial. The study essentially compared a near-maximal dose of solriamfetol to a placebo; it provides little insight into whether a lower dose might be effective or how outcomes differ between 75  and 150 mg. With no predefined low-dose group maintained, the supposed “dose-response” cannot be evaluated. This is a missed opportunity …
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Fifth, we question the choice and interpretation of the outcome measures, which may not be ideally suited to an ME/CFS population. The primary endpoint, the FSI, was originally developed and validated for assessing fatigue in cancer patients and survivors. While fatigue is common to many illnesses, the nature of ME/CFS fatigue is unique – notably the presence of post-exertional malaise (PEM), an exacerbation of symptoms after physical or mental exertion. The 2015 Institute of Medicine report identifies PEM as a cardinal feature of ME/CFS, absent in many other fatiguing illnesses. An outcome instrument designed for cancer-related fatigue may not capture this hallmark ME/CFS symptom or other nuances of ME/CFS fatigue. We are concerned that using the FSI (which focuses on fatigue severity, frequency, and interference in general might miss clinically important aspects of ME/CFS symptomatology and thus limit the validity of the findings. Furthermore, the authors interpret improvements in BRIEF-A scores as indicative of enhanced “executive functioning” and by extension improved cognitive fatigue. However, the BRIEF-A is a subjective rating inventory of perceived executive dysfunction in daily life …
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Finally, the study’s reliance on self-reported outcomes, with no objective or physiological measures, is a notable limitation – especially in a trial of a stimulant drug. All endpoints (fatigue scales, BRIEF-A, etc.) were patient-reported, which introduces potential bias. Participants on solriamfetol may have been unblinded by drug side effects and stimulation. Indeed, the most common adverse events were insomnia and headaches, effects likely noticeable to patients. If patients inferred they were on the active drug (due to such side effects or a subjective energizing effect), their expectancy could subconsciously influence questionnaire responses. This placebo expectancy bias is difficult to avoid when subjective outcomes are used in a drug with identifiable psychoactive properties …
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SNT Gatchaman said:
Letter to the editor —

“Too small to succeed?” Rethinking efficacy claims in a solriamfetol trial for ME/CFS
Zhihao Lei

Web | DOI | PDF | Journal of Psychopharmacology | Paywall
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It’s nice to have someone spell out the flaws. Have they been involved in anything related to ME/CFS before?

It seems like they are associated with Edinburgh and Cornell, and have been writing a substantial amount of letters:

ORCID

orcid.org orcid.org
 
Utsikt said:
It’s nice to have someone spell out the flaws. Have they been involved in anything related to ME/CFS before?

It seems like they are associated with Edinburgh and Cornell, and have been writing a substantial amount of letters:

ORCID

orcid.org orcid.org
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Based on that ORCID profile, this letter is likely AI generated and this person is likely not real.
 
InitialConditions said:
Based on that ORCID profile, this letter is likely AI generated and this person is likely not real.
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Well that's interesting. The content of the letter passed my immediate AI filter.

They have written an editorial for the BMJ.


Department of Statistics and Data Science, Cornell University, Ithaca, NY, USA​
School of Mathematics, University of Edinburgh, Edinburgh, UK​
​

As well as other publications with a range of institutions and odd email addresses.

A comprehensive statistical analysis of COVID-19 trends: Global and United States insights through ARIMA, regression, and spatial models

The COVID-19 pandemic has driven the need for accurate data analysis and forecasting to support public health decision-making. This study applied autoregressive integrated moving average (ARIMA) models and ARIMA models with exogenous variables to predict short-term trends in confirmed COVID-19...
www.accscience.com www.accscience.com

1 School of Mathematics, University of Edinburgh, Edinburgh, Scotland, United Kingdom​
2 Department of Biostatistics, School of Public Health, Brown University, Providence, Rhode Island, United States of America​
​
​
Analysis of Simpson’s Paradox and Its Applications


Department of Mathematics, University of Edinburgh, Edinburgh, The United Kingdom​
​
​
Here's the Dept. Maths academic page at University of Edinburgh with some familiar names and friendly faces. Hello Sjoerd Beentjes!

The email formats use people's names.
 
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InitialConditions said:
A Senior Research Fellow, and Fellow of the Royal Statistical Society!!, but a student at Cornell and previously Edinburgh!

it's all made up.
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Might just be a normal student trying to use LLM-assisted letters to get a publication count going?

If this really is LLM, I think it says something about the quality of the original research that it’s so easy to identify the flaws.
 
Utsikt said:
If this really is LLM, I think it says something about the quality of the original research that it’s so easy to identify the flaws.
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We do that here daily. And most of us have no clinical sciences background. LLMs can write full papers and even generate the data sets and code to go with them. Letters are child's play.
 
forestglip said:
A webpage for the above person: https://zlei2269.github.io/
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It says:

Honors and Awards​

  • Winner, Urban Views Category — University of Edinburgh Photography Competition (2024/25) [Link]
  • Year 4 and MMath Student Representative — School of Mathematics, University of Edinburgh, Sep. 2024 – May 2025 [Link]
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A person named Harry Lei on the first site. The second link doesn't work, but I found this page for a Harry Lei in that organization, and the photo looks like the person on the Github page.

I think it's a real person. Maybe they use AI to write lots of replies.
 
All those email addresses actually look consistent with his CV (on the webpage @forestglip linked). He claims to have moved around a lot, which would be normal for early career where you get a bunch of 1-2 year appointments. The ed.ac.uk ones seems to belong to Edinburgh and it wouldn’t be usual to have two, one with a prefix belonging to your dept or something.

That said I haven’t yet been able to confirm their CV itself. It’s be nice if one of these institutions had him on an old grad student page or something…
 
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