Psychotropic Medications and Dermatological Side Effects: An In-Depth Review

Round 1

Reviewer 1 Report

This in-depth review on dermatological side effects of psychotropics may be a useful paper for general consultation. However, some parts should be enriched and some part should be written again in order to make the reading smoother and more practical.

line 32: authors should proofread for mispelling issues (e.g. here is for United States)

lines 63-70: this paragraph should be more developed. Details on the topic are weak and may not add valuable information to someone who want to learn something from the topic of immunology. Many papers are available so far. Suggestion is too better explain the base of immunological patterns in psychiatric patients alone (a lot of papers talk about "psichiatry of chronic inflammatory diseases", such as lupus erythematosus, Rheumatoid Arthritis or even fibromyalgia) and in medication use alone, in order to compare, if any, differences and similaritis.

line 99: no language restriction added, might the authors explain if there were included other-than-english articles, how they were examinated?

line 102: no Inclusion or exclusion criteria were defined, Authors are invited to add them. Suggestion is even to report in a PRISMA-like diagram the process of screening of papers. It is not a Systemic review but it would better clarified the process used during the develop of this article (PRISMA have defined protocols for narrative or scoping review as well).

lines 205-207: Authors are invited to search for more recent reference, if present

lines 224-249: in this paragraph are listed the way of management of dermatological Side Effects. Authors should better develope this main topic. The suggestion is to devide in subparagraph, such as "management of common ADR" and " management of severe ADR". It would be useful for a future reader to better understand what literature suggest in clinical practice for each symptom enlighted. (May it depend on the severity only? May it depend on the psychiatric symptoms stability?)

lines 73-90 AND lines 143-173: both these paragraphs explain diagnostic features and clinical presentations. Authors may think to merge information in one paragraph only, in which may be underlined the role of dermatological inspection during a psychiatric visit and vice versa. Suggestion is also to mention diagnostic tools available to determine the Side Effects in psychiatric disorders. Several are used in clinical practice for general side effect burden. Many of these psychometric tools are drug or drug class specific (e.g. UKU as a eteroadministered, or GASS as a self administered, for Antipsychotics only) many of them may include dermatological symptoms. SOme of them are symptoms specific ( e.g. ASEX ofr sexual side effects), maybe it would be useful to know if there is any specific for dermatological issues in patients using psychotropics.

table 2: Authors may change the organization of this table to make it more suitable to future consultation: The suggestion is to organize for drug family, adding specific drug of each class with higher risk of dermatological ADR (not all drugs have the same impact in skin, despite the fact to be part of the same class of drugs)

lines 174-186: the suggestion is to elaborate contents to match the table. Authors are invited to devide for class of drugs, better with subtitles.

A minor revision for mispelling is needed

Author Response

This in-depth review on dermatological side effects of psychotropics may be a useful paper for general consultation. However, some parts should be enriched and some part should be written again in order to make the reading smoother and more practical.

line 32: authors should proofread for mispelling issues (e.g. here is for United States)

Response: We have proofread and rectified mispellings in the revised document.

lines 63-70: this paragraph should be more developed. Details on the topic are weak and may not add valuable information to someone who want to learn something from the topic of immunology. Many papers are available so far. Suggestion is too better explain the base of immunological patterns in psychiatric patients alone (a lot of papers talk about "psichiatry of chronic inflammatory diseases", such as lupus erythematosus, Rheumatoid Arthritis or even fibromyalgia) and in medication use alone, in order to compare, if any, differences and similaritis.

Response: Thank you for the suggestion. We have enriched the section with relevant details.

line 99: no language restriction added, might the authors explain if there were included other-than-english articles, how they were examinated?

Response: Non-english articles were first examined based on available english language titles/abstracts from the databases and later translated using Google translator tool for fetching relevant points from the main text.

line 102: no Inclusion or exclusion criteria were defined, Authors are invited to add them. Suggestion is even to report in a PRISMA-like diagram the process of screening of papers. It is not a Systemic review but it would better clarified the process used during the develop of this article (PRISMA have defined protocols for narrative or scoping review as well).

Response: Thank you for the suggestion! We have incorporated the inclusion and exclusion criteria in the main text as well as added a PRISMA flowchart for selected reports.

lines 205-207: Authors are invited to search for more recent reference, if present

Response: Thank you for the suggestion! Unfortunately we were unable to retrieve a more recent reference for the same.

lines 224-249: in this paragraph are listed the way of management of dermatological Side Effects. Authors should better develope this main topic. The suggestion is to devide in subparagraph, such as "management of common ADR" and " management of severe ADR". It would be useful for a future reader to better understand what literature suggest in clinical practice for each symptom enlighted. (May it depend on the severity only? May it depend on the psychiatric symptoms stability?)

Response: Thank you for the suggestion! We have restructured the section into the suggested format.

lines 73-90 AND lines 143-173: both these paragraphs explain diagnostic features and clinical presentations. Authors may think to merge information in one paragraph only, in which may be underlined the role of dermatological inspection during a psychiatric visit and vice versa. Suggestion is also to mention diagnostic tools available to determine the Side Effects in psychiatric disorders. Several are used in clinical practice for general side effect burden. Many of these psychometric tools are drug or drug class specific (e.g. UKU as a eteroadministered, or GASS as a self administered, for Antipsychotics only) many of them may include dermatological symptoms. SOme of them are symptoms specific ( e.g. ASEX ofr sexual side effects), maybe it would be useful to know if there is any specific for dermatological issues in patients using psychotropics.

Response: Thank you for the suggestion! We have incorporated the mentioned points.

table 2: Authors may change the organization of this table to make it more suitable to future consultation: The suggestion is to organize for drug family, adding specific drug of each class with higher risk of dermatological ADR (not all drugs have the same impact in skin, despite the fact to be part of the same class of drugs)

Response: The table is kept broad in the sense that it defines the class, class wise data was covered in previous review, so we have tried to incorporate additional information in the text, rather than making a different table.

lines 174-186: the suggestion is to elaborate contents to match the table. Authors are invited to devide for class of drugs, better with subtitles.

Response: The table is kept broad in the sense that it defines the class, class wise data was covered in previous review, so we have tried to incorporate additional information in the text, rather than making a different table.

Reviewer 2 Report

A decent paper about Psychotropic drugs and Dermatological Side Effects

manuscript can be of interest for the readers

A think for start, you should remove the ethnicity table from the Introduction

Or better, write that is mainly about the ethnicity in the table caption

then move it to a separate chapter maybe?

Since there is nothing about that in the title and abstract.

For sure it does not belong there

I like the structure of the article in rest.

Waiting for your revision.

Best regards,

Author Response

A decent paper about Psychotropic drugs and Dermatological Side Effects

manuscript can be of interest for the readers

A think for start, you should remove the ethnicity table from the Introduction

Or better, write that is mainly about the ethnicity in the table caption

then move it to a separate chapter maybe?

Since there is nothing about that in the title and abstract.

For sure it does not belong there

I like the structure of the article in rest.

Waiting for your revision.

Best regards,

Response: The caption on the table has now been changed to ethnic risk factors and genetic predisposition.

Reviewer 3 Report

The present review article (psychoactives-2739724), by Novonil Deb et al, entitled "Psychotropic Medications and Dermatological Side Effects: An In-depth review", gives a thorough account of the psychotropic medications, commonly prescribed for psychiatric disorders, which can have underappreciated dermatological side effects. The review explores the intricate relationship between psychotropic drugs and the skin, emphasizing the significance of recognizing and managing these side effects in clinical practice. It categorizes dermatological side effects associated with different classes of psychotropic medications. These include antidepressants, antipsychotics, mood stabilizers, and anxiolytics.

The article is concisely written and well documented. It is definetely of interest to the cognizant reader, and a  valuable comprehensive source of information to clinicians, researchers, and educators, acilitating better informed decision-making in the treatment of mental health disorders, while prioritizing skin health and overall well-being.

Author Response

The present review article (psychoactives-2739724), by Novonil Deb et al, entitled "Psychotropic Medications and Dermatological Side Effects: An In-depth review", gives a thorough account of the psychotropic medications, commonly prescribed for psychiatric disorders, which can have underappreciated dermatological side effects. The review explores the intricate relationship between psychotropic drugs and the skin, emphasizing the significance of recognizing and managing these side effects in clinical practice. It categorizes dermatological side effects associated with different classes of psychotropic medications. These include antidepressants, antipsychotics, mood stabilizers, and anxiolytics.

The article is concisely written and well documented. It is definetely of interest to the cognizant reader, and a  valuable comprehensive source of information to clinicians, researchers, and educators, acilitating better informed decision-making in the treatment of mental health disorders, while prioritizing skin health and overall well-being.

Response- Thank you for the appreciation

Reviewer 4 Report

The topic is very actual, safety is the most important principle in pharmacotherapy.

I have only several  concrete suggestions and remarks.

Ad introduction

Adverse cutaneous drug reactions(ACDRs) may be underreported for many reasons. The range of ACDRs frequency in the literature is  broad.

Suggestion:

 To add a short possible explanation (different data sources ?).

Ad 1.3. Clinical manifestation

To add information about photosensitivity  - this phenomenon is rare, however has practical impact. The authors mention photosensitivity as a rare ACDS, however we should take into consideration that this side effect is associated with SSRI, the most frequently prescribed antidepressants in all the world not only for depression but also for many others conditions ( Di Bartolomeo L, 2022). Drug-induced photosensitivity  is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, including phototoxicity (immediate, appears as an exaggerated sunburn)  and photoallergy - a delayed eczematous reaction. Pleas stress also how to improve sun exposure behaviours of patients at risk and  the lack a formal education about their condition.

Also add the mention about alopecia. Alopecia is very rare, however it present high psychic burden for the patient (Katrin Druschky), 2018)

Ad 2. Methodology

Please specify the sources of data ( registration studies, case reports, data from pharmacovigilance programmes)

Ad 4. Cutaneous Adverse Drug Reactions

Classification of adverse effects according to the class-specific drugs the Table 2. – please specify the terms dealing with frequency ( often, rare, very rare, in relation to placebo?)

Ad 6.3. Pharmacovigilance

 Pharmacovigilance is central to monitoring and managing the side effects generally
To add discussion about pharmacovigilance programmes- there are mentioned several programmes, which have different methodological approach. In Europa there is frequently cited the multicentre drug safety surveillance project Drug Safety in Psychiatry (Arzneimittelsicherheit in der Psychiatrie, AMSP). AMPS includes clinically relevant adverse reactions to all marketed psychotropic drugs in hospitalized psychiatric patients in German speaking countries. This programme started in 1993, the results have been published in impacted psychiatric journals.

Ad 7. Conclusions

Suggestions:

Briefly  mention that severe cutaneous adverse reaction are mostly associated with phenothiazine antipsychotics, carbamazepine  and barbiturates and  seen significantly less often with modern antidepressants (SSRI, dual antidepressants) and atypical antipsychotics  (Lange-Asschenfeldt Ch  , 2009) However, the modern psychotropics are used much more often (larger indications , comorbidity with somatic diseases…)

Author Response

The topic is very actual, safety is the most important principle in pharmacotherapy.

I have only several  concrete suggestions and remarks.

Ad introduction

Adverse cutaneous drug reactions(ACDRs) may be underreported for many reasons. The range of ACDRs frequency in the literature is  broad.

Suggestion:

 To add a short possible explanation (different data sources ?).

Response- Data source is mentioned

Ad 1.3. Clinical manifestation

To add information about photosensitivity  - this phenomenon is rare, however has practical impact. The authors mention photosensitivity as a rare ACDS, however we should take into consideration that this side effect is associated with SSRI, the most frequently prescribed antidepressants in all the world not only for depression but also for many others conditions ( Di Bartolomeo L, 2022). Drug-induced photosensitivity  is a common cutaneous adverse drug reaction, resulting from the interaction of ultraviolet radiations, including phototoxicity (immediate, appears as an exaggerated sunburn)  and photoallergy - a delayed eczematous reaction. Pleas stress also how to improve sun exposure behaviours of patients at risk and  the lack a formal education about their condition.

Response- A section on Drug induced photosensitivity has been added with effective measures.

Also add the mention about alopecia. Alopecia is very rare, however it present high psychic burden for the patient (Katrin Druschky), 2018)

 Response- A section on drug induced alopecia is added to the clinical picture section.

Ad 2. Methodology

Please specify the sources of data ( registration studies, case reports, data from pharmacovigilance programmes)

Response- The data sources and the type of included articles are mentioned as per the suggestion.

Ad 4. Cutaneous Adverse Drug Reactions

Classification of adverse effects according to the class-specific drugs the Table 2. – please specify the terms dealing with frequency ( often, rare, very rare, in relation to placebo?)

Response- The frequency column has been removes and the entire row is replaced by  incidence of adverse effects observed from previous studies. Ref no 10.
Ad 6.3. Pharmacovigilance

 Pharmacovigilance is central to monitoring and managing the side effects generally
To add discussion about pharmacovigilance programmes- there are mentioned several programmes, which have different methodological approach. In Europa there is frequently cited the multicentre drug safety surveillance project Drug Safety in Psychiatry (Arzneimittelsicherheit in der Psychiatrie, AMSP). AMPS includes clinically relevant adverse reactions to all marketed psychotropic drugs in hospitalized psychiatric patients in German speaking countries. This programme started in 1993, the results have been published in impacted psychiatric journals.

Response- Relevance and possible uses of the AMSP project is included in this section (marked in yellow), the sections adds that healthcare professionals can use the data in order to create awareness related to drug safety issues

Ad 7. Conclusions

Suggestions:

Briefly  mention that severe cutaneous adverse reaction are mostly associated with phenothiazine antipsychotics, carbamazepine  and barbiturates and  seen significantly less often with modern antidepressants (SSRI, dual antidepressants) and atypical antipsychotics  (Lange-Asschenfeldt Ch  , 2009) However, the modern psychotropics are used much more often (larger indications , comorbidity with somatic diseases…)

Response- The authors have discussed this and a suitable statement has been added in the conclusion part from the suggested study. The section is marked in yellow.

Round 2

Reviewer 1 Report

All issues have been resolved. Thanks for your contribution.