Reviewer's report
Title:Direct Acting Antivirals in Hepatitis C: A Systematic Review of
Neuropsychiatric Risks and Psychiatric Drug Interactions
Version: 3Date:27 March 2013
Reviewer: David Back
Reviewer's report:
This is an important topic and the authors have given us a thorough review which
will be useful to HCPs seeking to optimise the use of DAAs in the treatment of
Hep C.
I have some comments (mostly minor)
1. Page 2. Line 8. pharmaceutical companies?
2. Page 4 Line 13. Both agents inhibit P-gp and telaprevir may inhibit renal
transporters. These statements should be referenced.
3. Page 5. Line 4 & 6 of Methods. Some concern that the searches only went to
Sept 2012. This is such a fast moving field that I would strongly urge the authors
to include articles to March 2013 - else you are losing 6 months of possible
important material.
4. Page 6 Line 14. I would like to see some additional input here on the level of
evidence and make it clear that this was only done in the context of treatment of
depression.
5. Page 7 Line 13. Slightly confused. In Table 2 the notes state that Level 4 is
anecdotal or expert opinion whereas here it implies it is literature based. Clarifyl.
6. Page 8, Line 4. Somewhere (either here or Table 2) would like to see a
comment about the Dec 11 QT warning with escitalopram and citalopram.
7. Page 8 Line 8. Sentence beginning 'Therefore, selection .....' is not clear.
8. Page 8 Last line. Does not make sense. glucuronidation is conjugation!
9. Page 12 Line 8. Why should caution be exercised if there are no suspected
metabolic drug interactions. Clarify.
10. Page 14. Last lines. Do the authors consider that it is realistic that future drug
interaction studies will correlate changes in DAA and psychotropic drug levels
with HCV treatment outcomes and relapse. Most DDI studies have PK endpoints.
11. Table 2. Why if citalopram and escitalopram have the same metabolic
pathway will citalopram levels likely increase while escitalopram have been
shown to decrease with TVR?
12. Table 2. Need some comment for nefazodone.
13. Table 4. Clozapine. Is it realistic to advocate TDM?
14. Table 4. Paliperidone. I understood that this drug is substantially renally
excreted with little evidence for CYP2D6 or CYP3A4 in vivo.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Reviewer's report
Title:Direct Acting Antivirals in Hepatitis C: A Systematic Review of
Neuropsychiatric Risks and Psychiatric Drug Interactions
Version: 3Date:27 March 2013
Reviewer: David Back
Reviewer's report:
This is an important topic and the authors have given us a thorough review which
will be useful to HCPs seeking to optimise the use of DAAs in the treatment of
Hep C.
I have some comments (mostly minor)
1. Page 2. Line 8. pharmaceutical companies?
2. Page 4 Line 13. Both agents inhibit P-gp and telaprevir may inhibit renal
transporters. These statements should be referenced.
3. Page 5. Line 4 & 6 of Methods. Some concern that the searches only went to
Sept 2012. This is such a fast moving field that I would strongly urge the authors
to include articles to March 2013 - else you are losing 6 months of possible
important material.
4. Page 6 Line 14. I would like to see some additional input here on the level of
evidence and make it clear that this was only done in the context of treatment of
depression.
5. Page 7 Line 13. Slightly confused. In Table 2 the notes state that Level 4 is
anecdotal or expert opinion whereas here it implies it is literature based. Clarifyl.
6. Page 8, Line 4. Somewhere (either here or Table 2) would like to see a
comment about the Dec 11 QT warning with escitalopram and citalopram.
7. Page 8 Line 8. Sentence beginning 'Therefore, selection .....' is not clear.
8. Page 8 Last line. Does not make sense. glucuronidation is conjugation!
9. Page 12 Line 8. Why should caution be exercised if there are no suspected
metabolic drug interactions. Clarify.
10. Page 14. Last lines. Do the authors consider that it is realistic that future drug
interaction studies will correlate changes in DAA and psychotropic drug levels
with HCV treatment outcomes and relapse. Most DDI studies have PK endpoints.
11. Table 2. Why if citalopram and escitalopram have the same metabolic
pathway will citalopram levels likely increase while escitalopram have been
shown to decrease with TVR?
12. Table 2. Need some comment for nefazodone.
13. Table 4. Clozapine. Is it realistic to advocate TDM?
14. Table 4. Paliperidone. I understood that this drug is substantially renally
excreted with little evidence for CYP2D6 or CYP3A4 in vivo.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Please review this paper.
user
Reviewer's report
Title:Direct Acting Antivirals in Hepatitis C: A Systematic Review of
Neuropsychiatric Risks and Psychiatric Drug Interactions
Version: 3Date:27 March 2013
Reviewer: David Back
Reviewer's report:
This is an important topic and the authors have given us a thorough review which
will be useful to HCPs seeking to optimise the use of DAAs in the treatment of
Hep C.
I have some comments (mostly minor)
1. Page 2. Line 8. pharmaceutical companies?
2. Page 4 Line 13. Both agents inhibit P-gp and telaprevir may inhibit renal
transporters. These statements should be referenced.
3. Page 5. Line 4 & 6 of Methods. Some concern that the searches only went to
Sept 2012. This is such a fast moving field that I would strongly urge the authors
to include articles to March 2013 - else you are losing 6 months of possible
important material.
4. Page 6 Line 14. I would like to see some additional input here on the level of
evidence and make it clear that this was only done in the context of treatment of
depression.
5. Page 7 Line 13. Slightly confused. In Table 2 the notes state that Level 4 is
anecdotal or expert opinion whereas here it implies it is literature based. Clarifyl.
6. Page 8, Line 4. Somewhere (either here or Table 2) would like to see a
comment about the Dec 11 QT warning with escitalopram and citalopram.
7. Page 8 Line 8. Sentence beginning 'Therefore, selection .....' is not clear.
8. Page 8 Last line. Does not make sense. glucuronidation is conjugation!
9. Page 12 Line 8. Why should caution be exercised if there are no suspected
metabolic drug interactions. Clarify.
10. Page 14. Last lines. Do the authors consider that it is realistic that future drug
interaction studies will correlate changes in DAA and psychotropic drug levels
with HCV treatment outcomes and relapse. Most DDI studies have PK endpoints.
11. Table 2. Why if citalopram and escitalopram have the same metabolic
pathway will citalopram levels likely increase while escitalopram have been
shown to decrease with TVR?
12. Table 2. Need some comment for nefazodone.
13. Table 4. Clozapine. Is it realistic to advocate TDM?
14. Table 4. Paliperidone. I understood that this drug is substantially renally
excreted with little evidence for CYP2D6 or CYP3A4 in vivo.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
assistant