Is It Safe to Use Vasoconstrictors in Association Treated with Amitriptyline or Can It Potentiate Cardiovascular Effects? In Vivo Animal Study

Round 1

Reviewer 1 Report

This is a in vivo experimental study that aimed to evaluate changes in blood pressure of rats treated or not with amitriptyline after infiltration in the buccal sulcus and intravenous injection of epinephrine, felypressin and phenylephrine. The manuscript is clear, and the object is relevant for clinical reasons.

Some aspects need to become clearer:

·        The references are older than 5 years, only two of them are recent. It’s understandable that some references could be theoretical reference but not almost of them.

·        The methodology was very well outlined and described, but reporting of in vivo experiments (ARRIVE) must be better described as some points as not clear (ex. Sample size)

·        As it is an animal experiment, the paper must be reviewed as could be differences in the results in human so, these limitations must be explicit throughout the paper (abstract, discussion and conclusion) .

Author Response

Response to Reviewer 1 Comments

This is a in vivo experimental study that aimed to evaluate changes in blood pressure of rats treated or not with amitriptyline after infiltration in the buccal sulcus and intravenous injection of epinephrine, felypressin and phenylephrine. The manuscript is clear, and the object is relevant for clinical reasons.

Some aspects need to become clearer:

1. The references are older than 5 years, only two of them are recent. It’s understandable that some references could be theoretical reference but not almost of them.

Response: Thank you! New references have been added

Urits, I.; Peck, J.; Orhurhu, M.S.; Wolf, J.; Patel, R.; Orhurhu, V.; Kaye, A.D.; Viswanath, O. Off-Label Antidepressant Use for Treatment and Management of Chronic Pain: Evolving Understanding and Comprehensive Review. Curr. Pain Headache Rep. 2019, 23, 66, doi:10.1007/s11916-019-0803-z.

Saraghi, M.; Golden, L.; Hersh, E. V Anesthetic Considerations for Patients on Antidepressant Therapy - Part II. Anesth. Prog. 2018, 65, 60–65, doi:10.2344/anpr-65-01-10.

Artigas, F.; Nutt, D.J.; Shelton, R. Mechanism of Action of Antidepressants. Psychopharmacol. Bull. 2002, 36 Suppl 2, 123–132.

Ouanounou, A.; Ng, K. Medical Management, Orofacial Findings, and Dental Care for the Client with Major Depressive Disorder. Can. J. Dent. Hyg.  CJDH = J. Can. l’hygiene Dent.  JCHD 2019, 53, 172–177.

Harbell, M.W.; Dumitrascu, C.; Bettini, L.; Yu, S.; Thiele, C.M.; Koyyalamudi, V. Anesthetic Considerations for Patients on Psychotropic Drug Therapies. Neurol. Int. 2021, 13, 640–658, doi:10.3390/neurolint13040062.

2. The methodology was very well outlined and described, but reporting of in vivo experiments (ARRIVE) must be better described as some points as not clear (ex. Sample size)

Response: Thank you. The sample size is described in the first paragraph of the material and methods. 2.1 Animals and experimental groups

“Forty-two male Wistar rats of 45-day-old, with bodyweight between 300 and 500 g, from the Central Animal Facility of the Medicine School of Ribeirão Preto (FMRP-USP), were randomly allocated into two groups: 21 animals without treatment (control) and 21 animals treated with the tricyclic antidepressant amitriptyline (amitriptyline treated).”

3. As it is an animal experiment, the paper must be reviewed as could be differences in the results in human so, these limitations must be explicit throughout the paper (abstract, discussion and conclusion).

Response: Thank you. New paragraphs have been added to the discussion and conclusion.

Discussion: Line 298-299: “The results obtained in this research cannot be faithfully extrapolated to human beings, but they can contribute and guide future studies in human beings.”

Conclusion: Line 300 -312 – “Despite our study being in animals, our results may contribute to future studies evaluating the safety of dental anesthesia procedures for patients receiving this type of medication.”

Reviewer 2 Report

This is a superb study, thus I recommend accepting it.

Significant numbers of rats were utilized by the writers (42 in total).

Methods for measuring blood pressure  are reproducible.

Vasoconstrictor dosage was appropriate.

Results are significant and of importance to clinical dentistry.

It is essential for dentists who treat patients with systemic disorders to promote for the safety of vasoconstrictors. As life expectancy rises, the number of dental patients with systemic diseases will increase. Hence any strong evidence regarding the safety of the drugs used in dental care is essential.

Author Response

thank you