The Emerging Role of Pharmacotherapy in Obstructive Sleep Apnea

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This is a review about pharmagology used in the treatment of OSA. First it is mandatory to explain the individual search strategy for each of the following bibliographic databases and  the methodology used in the  selected studies.

The review  has not been previouly registered so it should be calle a narrative review.

Line 38 include MYOFUNCTIONAL THERAPY pleasa reference Carrasco-Llatas M, . The Role of Myofunctional Therapy in Treating Sleep-Disordered Breathing: A State-of-the-Art Review. Int J Environ Res Public Health. 2021 Jul 8;18(14):7291. doi: 10.3390/ijerph18147291. PMID: 34299742; PMCID: PMC8306407.

Line 75 increased genioglousus stimulation. What is the objetive test to assure this?

If not please refer as a limitation of this afirmation line 75.

Please include figures about the way of mechanism of every medication .

Also it will be interested to group the drugs for it OSA phenotype. Please include a figure based on Eckert phenotypes and the utility of the drugs.

Author Response

This is a review about pharmacology used in the treatment of OSA. First it is mandatory to explain the individual search strategy for each of the following bibliographic databases and the methodology used in the selected studies.

• Thank you for this valuable feedback and for taking the time to review our article. We have now included our search strategy and the methodology used in the selected studies in the Introduction section.

The review has not been previously registered so it should be called a narrative review.

• Thank you. We have replaced “review article” with “narrative review article” in the abstract and introduction section of the article.

Line 38 include MYOFUNCTIONAL THERAPY please reference Carrasco-Llatas M, . The Role of Myofunctional Therapy in Treating Sleep-Disordered Breathing: A State-of-the-Art Review. Int J Environ Res Public Health. 2021 Jul 8;18(14):7291. doi: 10.3390/ijerph18147291. PMID: 34299742; PMCID: PMC8306407.

• Thank you for sharing this alternative OSA therapy and reference. We have now included this article as a reference in the Introduction.

Line 75 increased genioglossus stimulation. What is the objective test to assure this?

If not please refer as a limitation of this affirmation line 75.

• Thank you for this feedback. Genioglossus stimulation is measured through genioglossus electromyographic activity. We have now mentioned this objective test in line 75.

Please include figures about the way of mechanism of every medication.

• Thank you for this valuable suggestion. We have now incorporated a table for the mechanism of these medications.

Also, it will be interested to group the drugs for it OSA phenotype. Please include a figure based on Eckert phenotypes and the utility of the drugs.

• The OSA phenotypes and the implications for these drugs in future clinical practice is now included in the Discussion section. We would like to note that we had to limit the extent of the discussion based on the scope of this article and word limits.

Reviewer 2 Report

Comments and Suggestions for Authors

The submitted review article reviewed the mechanism behind the current pharmacotherapy available for Obstructive Sleep Apnea (OSP) and potential future drug targets. The review focuses on three main sections: 1. Noradrenergic and Antimuscarinic agents and a review of various trials 2. Glucagon-like-peptide-1 receptor agonists (GLP-1RA) as a target and review of various trials 3. Alternative medication focuses on drug molecules that target the serotonin pathway and regulate muscle tension or respiratory center.

Section 1 is written as a summary of two systemic reviews and Table 1 provides details of a few more studies.  However, the details of the mechanism are not mentioned in depth for these agents.  What these drugs are not able to achieve in these trials and what knowledge gap these drugs fill is not mentioned. What are the author's thoughts on this drug being a good or bad candidate for future studies? All this information is missing, and this section reads as a summary of that systemic review without any originality of the author's thought process.

Sections 2 and 3 are written in much more depth and talk more about individual papers rather than summaries of systemic reviews. But again, I don’t see a thought process from the authors as to why they think GLP-1RA and other alternative targets might be the better target and what is the key message from all the published papers.

 

The introduction doesn’t provide readers with the purpose of this review. What question and knowledge gap might be filled? They need to rewrite the introduction and explain why the review is needed. 

Author Response

The submitted review article reviewed the mechanism behind the current pharmacotherapy available for Obstructive Sleep Apnea (OSP) and potential future drug targets. The review focuses on three main sections: 1. Noradrenergic and Antimuscarinic agents and a review of various trials 2. Glucagon-like-peptide-1 receptor agonists (GLP-1RA) as a target and review of various trials 3. Alternative medication focuses on drug molecules that target the serotonin pathway and regulate muscle tension or respiratory center.

Section 1 is written as a summary of two systemic reviews and Table 1 provides details of a few more studies.  However, the details of the mechanism are not mentioned in depth for these agents.  What these drugs are not able to achieve in these trials and what knowledge gap these drugs fill is not mentioned. What are the author's thoughts on this drug being a good or bad candidate for future studies? All this information is missing, and this section reads as a summary of that systemic review without any originality of the author's thought process.

• Thank you for sharing your perspective on our article and taking the time to review this article. We appreciate your suggestion, and we have added Table 3 to highlight the mechanisms of action for these agents. Overall, the authors attempted to remain objective and to present current studies and data in a neutral manner to allow the reader to develop their own conclusions. We have now elaborated in the Discussion section about the drug candidates for future studies and the knowledge gap that these drugs fill to provide greater context into the overall potential for these medications.

Sections 2 and 3 are written in much more depth and talk more about individual papers rather than summaries of systemic reviews. But again, I don’t see a thought process from the authors as to why they think GLP-1RA and other alternative targets might be the better target and what is the key message from all the published papers.

• Thank you for sharing this valuable insight. We have elaborated in the Discussion about the efficacy and future outlook for OSA pharmacotherapy. We attempted to remain objective to allow the readers to draw their conclusions, yet we do believe that the future of OSA is promising, notably GLP-1 agonists, so we have now included this.

The introduction doesn’t provide readers with the purpose of this review. What question and knowledge gap might be filled? They need to rewrite the introduction and explain why the review is needed. 

• Thank you for your feedback regarding the Introduction. We have now added the purpose of the review with the knowledge gap that is intended to be filled and the need for such a review with context in the literature.

Reviewer 3 Report

Comments and Suggestions for Authors

Jaganathan et al describe & demonstrated significant emerging role of pharmacotherapy in obstructive sleep apnea.

Line 45-46 - I think it is better to include example of what drugs involve in OSA pharmacotherapy.

Line 59-71 Is there any different in using - & plus for example reboxetine-hyoscine & atomoxetine plus biperiden - please standardize

page 5 - Blackman et al - Is 3 mg of Liraglutide is therapeutic dose?  please explain in discussion

 

Author Response

Jaganathan et al describe & demonstrated significant emerging role of pharmacotherapy in obstructive sleep apnea.

Line 45-46 - I think it is better to include example of what drugs involve in OSA pharmacotherapy.

• We appreciate this insight, and we want to thank you for your time in reviewing our article. We have now included examples of the specific drugs we discuss in line 45-46 of the Introduction

Line 59-71 Is there any different in using - & plus for example reboxetine-hyoscine & atomoxetine plus biperiden - please standardize

• Thank you for this feedback. The nomenclature has now been standardized by removing “plus” and only hyphenating drug combinations.

page 5 - Blackman et al - Is 3 mg of Liraglutide is therapeutic dose?  please explain in discussion

• The 3.0 dose of liraglutide was selected due to approval of 3.0 mg liraglutide for weight management purposes. This rationale has now been included in the discussion of Blackman et al.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

Authors have added succesfully the changes suggested by this reviewer.

Reviewer 2 Report

Comments and Suggestions for Authors

I am satisfied with the authors response.