PONE-D-25-14184Post-marketing Safety of Solriamfetol: A Retrospective Pharmacovigilance Study Based on the US Food and Drug Administration Adverse Event Reporting System

PLOS ONE

Dear Dr. Zhu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jun 20 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Christian Veauthier, M.D.

Academic Editor

PLOS ONE

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 [This work is financially supported by grants from the Jiangsu Pharmaceutical Association (Grant No. H202311)]. 

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

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Additional Editor Comments (if provided):

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: No

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study analizes AEs of solriamfetol retrospectively using real-world data.

P4 line 55: Authors should clearly state if they refer to EDS in general, in narcolepsy or in OSA. Otherwise the mentioning of specific wake promoting agents does not make sense, since they are approved for certain indications only. Pitolisant as alternative has not been mentioned.

Table 1: it should be mentioned that the prescription in Europe is much more restricted to the approved indications as in the US, which could attribute to the high amount of AEs in the US.

Table 2 needs a legend of abbreviations. The AEs are rather unspecfic. There seems to be much more information about different psychiatric disorders and cardiac symptoms as can be seen in table 3. Could drug ineffectiveness be dependant on dosage or comedication? There is no information about this. Therefore it would be nice to have some more information about the settings of the FAERS database.

What are general disorders, please explain in more detail.

What do you consider to be poisoning? Is this term directly related to intake of solriamfetol only or is it including all preexisting forms of medication, alcohol and drug abuse etc.?

I suggest to give table 3 a better structure by listing all psychiatric disorders first according to frequency followed by nervous system disorders etc.

P19 line 163: Since most AEs were reported within the first 7 days it would be good to discuss if these were in fact substance related or unspecific. Moreover the most important AE for women would be spontaneous abortion. This needs special consideration, because it would imply not to prescribe solriamfetol for women with child bearing potential.

Given all the limitation of the FAERS database at the end of the discussion, the conclusion should be much more cautious. It should mention that the most common side effets of the initial solriamfetol studies were confirmed. I suggest to mention the study limitations clearly in the method chapter to shed a light on the presented results, instead of presenting them at the very end.

The discussion should certainly comment the decline of AEs from 2023 on.

Reviewer #2: The paper by Wu and Zhu describes the frequency of AEs due to Solriamfetol treatment. They used the FEARS database for analysis.

The paper is overall well structured and written.

The paper has many limitations and severe concerns that need to be addressed:

1.- Funding: Please elaborate further on the funding of this project. I could not find any additional information on the Grant No. H202311.

2.- Abstract: “EDS…and may be life-threatening”. This is true in the context of car accident etc., but the wording here is a little unfortunate. Please rephrase this sentence.

3.- Introduction: For a better description of what is EDS you should consider Lammers et al., Sleep Med Rev, 2020.

4.- Introduction: I disagree with your statement “Although continuous positive airway pressure is effective, EDS may persist in patients with OSA, almost all of whom undergo pharmacological therapy [8]”. Please provide data on this statement. I´m not aware of such data. Only some patients undergo pharmacological therapy, not “almost all”.

5.- Introduction: Next, you describe “Modafinil and armodafinil promote arousal and are currently used as first-line treatments for EDS in adults”. The reference you provide does not refer to EDS in OSA or in narcolepsy. You´re not precise here and are mixing up different things. Please clarify in the introduction what are current pharmacological recommendations for EDS in narcolepsy, for EDS in OSA and for other, if available.

6.- Methods/ Discussion/ Conclusions: Limitation of FEARS database: It includes data from “various sources, including medical professionals, consumers,…”. And as described in the results, mostly consumers (>50%) reported AEs. The FEARS database itself describes all its limitations on their webpage. You mention most, but not all of them. Further, for a lot of data “unknown” or “other” is described. I.e. you cannot make strong statement on age “median age was 40”, if 78% of data on age are “unknown”. This also refers to other points in your discussion.

7.- The discussion is too long and repeats results.

8.- Conclusion: I disagree with your conclusion. It is very worrying that, despite the very limited data available and all the serious limitations, you end up concluding that “serious AEs” occur with solriamfetol. The side effects mentioned generally correspond to the known side effects and no real statement can be made about the frequency due to the given limitations. What are the serious AEs?

9.- Most AEs are reported in the context of treatment for narcolepsy. This is not mentioned or discussed. Many patients with narcolepsy receive co- medication or polypharmacy. Another limitation, which is not mentioned.

10.- As further recommendation: In my opinion, it would be interesting if you could split the data sets into a part with results from consumer reports and a part with reports from physicians and compare results.

Reviewer #3: This paper summarizes the postmarketing reports of adverse effects of solriamfetol. The methodology and statistical analysis is sound, the manuscript is written well and the discussion is appropriate, addressing the relevant imitations of such methodology.

The only point I am curious about is the details of serious adverse effects such as hospitalization and death. If possible, it would be very enlightening to add the details regarding these serious AEs, like why the patients were hospitalized or left disabled etc.

Other than that, I have no further comments. It was a pleasure to review this paper.

Thank you.

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Reviewer #1: Yes:  Geert Mayer

Reviewer #2: No

Reviewer #3: No

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PONE-D-25-14184R1Post-marketing Safety of Solriamfetol: A Retrospective Pharmacovigilance Study Based on the US Food and Drug Administration Adverse Event Reporting SystemPLOS ONE

Dear Dr. Zhu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. ==============================

You have addressed the critical comments of the experts; unfortunately, methodological and substantive weaknesses continued to emerge during the review, which I would like to explain:

On the one hand, some reviewers criticized the fact that the data are not new and does not add any significant information to the data already published, but this is not a criterion for publication in Plos One.

Secondly, and more important, after inviting additional reviewers, there are also points of content that make publication in the current version impossible. The basic problem here seems to be that You are writing an article about a molecule (Solriamfetol) and not about a therapy for a distinct disorder. The situation would be completely different if the side effects of treating narcolepsy patients with Solriamfetol had been evaluated – or OSA patients with Solriamfetol…. But different indications are being lumped together here. Moreover, there seem to be also patients without narcolepsy or OSA? And there is little information about comorbidities. But the effects can only be meaningfully assessed if the indication and comorbidities are also known. Otherwise, this should have to be described as a serious methodological limitation (e.g. how many patients with elevated blood pressure already had elevated blood pressure before or were taking antihypertensives? Did this only occur in sleep apnea patients or also in narcolepsy patients?).

Therefore, before publication in Plos One, a fundamental major revision of the article would be necessary, highlighting the methodological shortcomings mentioned, and we cannot guarantee that the article will be accepted next time. In addition, I also refer to further comments from the reviewers.

==============================

Please submit your revised manuscript by Aug 15 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Christian Veauthier, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments:

You have addressed the critical comments of the experts; unfortunately, methodological and substantive weaknesses continued to emerge during the review, which I would like to explain:

On the one hand, some reviewers criticized the fact that the data are not new and does not add any significant information to the data already published, but this is not a criterion for publication in Plos One.

Secondly, and more important, after inviting additional reviewers, there are also points of content that make publication in the current version impossible. The basic problem here seems to be that You are writing an article about a molecule (Solriamfetol) and not about a therapy for a distinct disorder. The situation would be completely different if the side effects of treating narcolepsy patients with Solriamfetol had been evaluated – or OSA patients with Solriamfetol…. But different indications are being lumped together here. Moreover, there seem to be also patients without narcolepsy or OSA? And there is little information about comorbidities. But the effects can only be meaningfully assessed if the indication and comorbidities are also known. Otherwise, this should have to be described as a serious methodological limitation (e.g. how many patients with elevated blood pressure already had elevated blood pressure before or were taking antihypertensives? Did this only occur in sleep apnea patients or also in narcolepsy patients?).

Therefore, before publication in Plos One, a fundamental major revision of the article would be necessary, highlighting the methodological shortcomings mentioned, and we cannot guarantee that the article will be accepted next time. In addition, I also refer to further comments from the reviewers.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

Reviewer #5: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1:  The paper has improved in clarity by responding in depth to all the reviewers comments. However the "real wolrd data" presented through the FAERS data analysis does not really add anything new to the knowlege about solriamfetol

Reviewer #3:  I have no further comments. I believe, within the constraints of the methodology and dataset employed, this is the most that can be reasonably achieved.

Thank you.

Reviewer #4:  (No Response)

Reviewer #5:  As a clinician, I find it difficult to know exactly what to do with the data presented. Who is reporting in the FAERS and why? It is also not clear how this report on solriamfetol compares with reports on other similar drugs or drugs for similar indications.

For me, it is also not entirely clear from the current description exactly what kind of statistics were applied and how to fully understand them. But that is not crucial for the more general discussion of what to do with data from databases like this.

Apparently, most reports are from people who do not use solriamfetol for narcolepsy or OSAS. It then makes an addition, which is difficult for me to understand, that ‘the most frequently reported indication for solriamfetol was narcolepsy (596, 38.45%), followed by OSA (57, 3.68%)’. All other indications thus constitute < 3.68% of the total group. This implies that at least 15 other indications for solriamfetol were reported! Moreover, if I understand it correctly, the most often reported is that the drug is not effective. Personally, I would not interpret that as an AE.

Finally, methodological issues aside, what is reported on AEs is not really new or unexpected.

Nevertheless, the previous reviewer comments have been adequately addressed.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #3: No

Reviewer #4: Yes:  Markku Partinen

Reviewer #5: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

<div>PONE-D-25-14184R2Post-marketing Safety of Solriamfetol: A Retrospective Pharmacovigilance Study Based on the US Food and Drug Administration Adverse Event Reporting SystemPLOS ONE

Dear Dr. Zhu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. The manuscript is significantly better and should be published soon, but there are still errors in Table 2:

The first column of Table 2 is labeled “Preferred Terms” and the second column is labeled “System Organ Class”. There seam to be obvious errors here: e.g., the organ “Renal and urinary disorders” is mentioned for the preferred term “cataplexy”. What does cataplexy have to do with renal and urinary disorders?

Or Sleep attacks with neoplasms? On the other hand, some information is incomprehensible: for example, why does “Suicidal intention” is mentionned under "investigations"? Readers cannot understand this without a comment in the legend. 

The entire Table 2 appears to be full of errors. Please read carefully before resubmission all tables and ensure that the tables are error-free. 

Please submit your revised manuscript by Oct 03 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Christian Veauthier, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

1. If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: All comments have been addressed

Reviewer #5: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Yes

Reviewer #5: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

Reviewer #5: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #5: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: Although this study inherently suffers from the limitations of utilizing FAERS as the data source, I do not think any additional revisions could improve the manuscript at this point. I do not have any further comments.

Reviewer #5: The previous comments have been properly addressed.

But, something went wrong in Table S2: the second column is not correctly matched to the first column. Whether there is possibly also an error in the other columns I cannot determine.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #3: No

Reviewer #5: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

PONE-D-25-14184R3Post-marketing Safety of Solriamfetol: A Retrospective Pharmacovigilance Study Based on the US Food and Drug Administration Adverse Event Reporting SystemPLOS ONE

Dear Dr. Zhu,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Unfortunately, I have one more comment to make: 

in Table 2, the preferred term “sleepiness” is assigned to system class “psychiatric disorder.” 

I find this difficult to understand given that the article is about narcolepsy and daytime sleepiness, 

and it reveals that the authors have no concept of daytime sleepiness and think that sleepiness is psychologically induced. That is not correct: Sleep apnea can cause sleepiness. Narcolepsy can cause sleepiness as well: neither is a psychiatric disorder. Sleepiness per se is not psychiatric. Please change the organ class.

Please submit your revised manuscript by Oct 18 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
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Christian Veauthier, M.D.

Academic Editor

PLOS ONE

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Post-marketing Safety of Solriamfetol: A Retrospective Pharmacovigilance Study Based on the US Food and Drug Administration Adverse Event Reporting System

PONE-D-25-14184R4

Dear Dr. Zhu,

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Kind regards,

Christian Veauthier, M.D.

Academic Editor

PLOS ONE

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