Antipsychotic Polypharmacy-Related Cardiovascular Morbidity and Mortality: A Comprehensive Review
, Emily D. Ellis 2, Laura M. Nussdorf 2, Taylor W. Hill 2, Elyse M. Cornett 3, Adam M. Kaye 4 and Alan D. Kaye 3Round 1
Reviewer 1 Report
This is a narrative review on the antipsychotic polypharmacy related cardiovascular morbidity and mortality. The paper is well-written and it is of interest for the journal. However, several minor changes should be made before publishing it.
In the abstract section, the authors reported that schizophrenia is an idiopathic disorder. I would prefer to remove the term "idiopathic" because it can be confusing.
The authors should describe in the abstract section how they conducted the review, which methods did they use? Although it seems to be narrative review, it would be useful to describe how they did the search, which databases, timeline, inclusion criteria, etc).
The introduction section is brief. I would recommend to expand it by adding an explanation about the biological systems implicated in the etiopathogenesis of psychosis. The biological underpinnings of treatment response in delusional psychoses should be briefly presented.
Age and menopause are potential predictors for the occurrence of antipsychotic adverse-events. I consider that it is necessary to introduce these concepts in the introduction section. There are several works about the pharmacotherapy of schizophrenia in postmenopausal women that may be useful to cite and describe.
I consider that the section of "antipsychotics" can be divided into two subsections: typical and atypical antipsychotics.
The section about "cardiac adverse effects and non-antipaychotic medications" should be renamed as for instance, "interactions between antipsychotics and non-psychotropic medications", as the main aim of the paper was to summarize evidence of the effects of antipsychotics.
CYP3A4 is one of the most important enzymes responsible for the metabolism of antipsychotic drugs. I would recommend to expand the last paragraph of this section ("antibiotics"). There are several works about the use of pharmacogenetic intervention for the improvement of the safety and selection of profile of antipsychotic treatments.
The effects of age and menopause should be highlighted in the conclusions section as they both alter the dynamics and kinetics of antipsychotic drugs.
Author Response
This is a narrative review on the antipsychotic polypharmacy related cardiovascular morbidity and mortality. The paper is well-written and it is of interest for the journal. However, several minor changes should be made before publishing it.
In the abstract section, the authors reported that schizophrenia is an idiopathic disorder. I would prefer to remove the term "idiopathic" because it can be confusing.
Answer: We absolutely agree with this point. We have removed the term from the revision in the abstract and the introduction.
The authors should describe in the abstract section how they conducted the review, which methods did they use? Although it seems to be narrative review, it would be useful to describe how they did the search, which databases, timeline, inclusion criteria, etc).
Answer: That is correct. This was a narrative review. We added language to the manuscript to make this clear.
The introduction section is brief. I would recommend to expand it by adding an explanation about the biological systems implicated in the etiopathogenesis of psychosis. The biological underpinnings of treatment response in delusional psychoses should be briefly presented.
Answer: A small part regarding this was added to the introduction.
Age and menopause are potential predictors for the occurrence of antipsychotic adverse-events. I consider that it is necessary to introduce these concepts in the introduction section. There are several works about the pharmacotherapy of schizophrenia in postmenopausal women that may be useful to cite and describe.
Answer: This is a good point. This was added to the introduction in a short paragraph.
I consider that the section of "antipsychotics" can be divided into two subsections: typical and atypical antipsychotics.
Answer: This has been changed in the revised manuscript
The section about "cardiac adverse effects and non-antipsychotic medications" should be renamed as for instance, "interactions between antipsychotics and non-psychotropic medications", as the main aim of the paper was to summarize evidence of the effects of antipsychotics.
Answer: This has been changed in the revised manuscript
CYP3A4 is one of the most important enzymes responsible for the metabolism of antipsychotic drugs. I would recommend to expand the last paragraph of this section ("antibiotics"). There are several works about the use of pharmacogenetic intervention for the improvement of the safety and selection of profile of antipsychotic treatments.
Answer: This has been expanded in the revised manuscript
The effects of age and menopause should be highlighted in the conclusions section as they both alter the dynamics and kinetics of antipsychotic drugs.
Answer: This has been added in the revised manuscript
Reviewer 2 Report
My suggestions :
- Could you introduce the psychosis a little bit more in detail in the introduction?
- A few figures on pathways, how the antipsychotic drugs would lead to cardiac issues would improve the manuscript.
- I would add a short chapter on the potential alternative drugs, which have no risk or lower risk for cardiac issues
- Did they use any animal models to study cardiac issues in antipsychotic drugs? Authors may mention briefly the animal models.
Author Response
My suggestions :
- Could you introduce the psychosis a little bit more in detail in the introduction?
Answer: Absolutely! This has been added to the manuscript.
- A few figures on pathways, how the antipsychotic drugs would lead to cardiac issues would improve the manuscript.
Answer: We didn’t want to clog everything up with too many figures, however, we did include one that we feel is simple to understand with an example of Haldol.
- I would add a short chapter on the potential alternative drugs, which have no risk or lower risk for cardiac issues
Answer: The issue with that is that there really aren’t any potential alternative drugs for psychosis that would have no risk of cardiac issues. Some do have a lower risk of not expanding the QTc interval but it’s not zero and it still happens so dividing them into no risk or low risk isn’t a great idea that could lead to the misconception that these are without risk and would confuse the reader.
- Did they use any animal models to study cardiac issues in antipsychotic drugs? Authors may mention briefly the animal models.
Answer: There are a few. We added this to the beginning of the clinical studies section.
Round 2
Reviewer 2 Report
Authors fulfilled my suggestions. Thank you.
