Reviewer's report
Title:Direct Acting Antivirals in Hepatitis C: A Systematic Review of
Neuropsychiatric Risks and Psychiatric Drug Interactions
Version: 3Date:9 April 2013
Reviewer: peter hauser
Reviewer's report:
Major Compulsory Revisions
1. none
Minor Essential Revisions
1. it is important to clarify that the neuropsychiatric side effects of antiviral
therapy including daa addition to interferon alpha is very likely an underestimate
as pharma has sponsored these studies and subjects with psychiatric illness are
generally excluded (even given that there is a comparision group of subjects on
interferon and not receiving DAAs). similarly the lifetime prevalence of psychiatric
illness in people with HCV is very likely an underestimate as it is based on
chart/clinical diagnosis and subject were not interviewed with psychiatric
diagnostic instruments.
2. the assumption that 'poorly controlled psychiatric illness may compromise
adherence....' is not supported in the literature and perpetuates a myth that
psychiatrically ill people are not compliant with medications and therefore should
not be offered antiveral therapy. also a large US Veteran Affairs study found no
significant decrease among mild and moderate alcohol drinkers (but did in heavy
drinkers) in SVR. Similarly Sylvestre found no significant decrease in SVR for
intermittant IV drug users.
3. there are certain references that have not been included- Pariate studies- see
Lancet 1999 among others, the Sylvestre study, the first prospective study of
interferon induced depression by Hauser in the journal molecular psychiatry
(2002), the US Veteran Affairs study that examined the effects of alcohol use on
SVR in Veterans with HCV, studies of people with stable psychiatric illness who
received antiviral therapy among others.
4. there is an implication that escitalopram is the antidepressant of choice for
treatment of interferon-induced depression, which may be an artifact of phrama
sponsored trials. generally SSRIs as a class and one could extrapolate that most
antidepressants are efficacious in treating interferon-induced depression and that
selection of an antidepressant may be guided by side effects profiles and DDI
with DAA.
Discretionary Revisions-
1.consider another word for 'backbone' of HCV therapy.
2. expand on DDI between DAA and lamotrigine as severe rash is a side effect of
DAAs and lamotrigine is associated with rash and in particular Steven's Johnson
syndrome
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Direct Acting Antivirals in Hepatitis C: A Systematic Review of
Neuropsychiatric Risks and Psychiatric Drug Interactions
Version: 3Date:9 April 2013
Reviewer: peter hauser
Reviewer's report:
Major Compulsory Revisions
1. none
Minor Essential Revisions
1. it is important to clarify that the neuropsychiatric side effects of antiviral
therapy including daa addition to interferon alpha is very likely an underestimate
as pharma has sponsored these studies and subjects with psychiatric illness are
generally excluded (even given that there is a comparision group of subjects on
interferon and not receiving DAAs). similarly the lifetime prevalence of psychiatric
illness in people with HCV is very likely an underestimate as it is based on
chart/clinical diagnosis and subject were not interviewed with psychiatric
diagnostic instruments.
2. the assumption that 'poorly controlled psychiatric illness may compromise
adherence....' is not supported in the literature and perpetuates a myth that
psychiatrically ill people are not compliant with medications and therefore should
not be offered antiveral therapy. also a large US Veteran Affairs study found no
significant decrease among mild and moderate alcohol drinkers (but did in heavy
drinkers) in SVR. Similarly Sylvestre found no significant decrease in SVR for
intermittant IV drug users.
3. there are certain references that have not been included- Pariate studies- see
Lancet 1999 among others, the Sylvestre study, the first prospective study of
interferon induced depression by Hauser in the journal molecular psychiatry
(2002), the US Veteran Affairs study that examined the effects of alcohol use on
SVR in Veterans with HCV, studies of people with stable psychiatric illness who
received antiviral therapy among others.
4. there is an implication that escitalopram is the antidepressant of choice for
treatment of interferon-induced depression, which may be an artifact of phrama
sponsored trials. generally SSRIs as a class and one could extrapolate that most
antidepressants are efficacious in treating interferon-induced depression and that
selection of an antidepressant may be guided by side effects profiles and DDI
with DAA.
Discretionary Revisions-
1.consider another word for 'backbone' of HCV therapy.
2. expand on DDI between DAA and lamotrigine as severe rash is a side effect of
DAAs and lamotrigine is associated with rash and in particular Steven's Johnson
syndrome
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
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:9 April 2013
Reviewer: peter hauser
Reviewer's report:
Major Compulsory Revisions
1. none
Minor Essential Revisions
1. it is important to clarify that the neuropsychiatric side effects of antiviral
therapy including daa addition to interferon alpha is very likely an underestimate
as pharma has sponsored these studies and subjects with psychiatric illness are
generally excluded (even given that there is a comparision group of subjects on
interferon and not receiving DAAs). similarly the lifetime prevalence of psychiatric
illness in people with HCV is very likely an underestimate as it is based on
chart/clinical diagnosis and subject were not interviewed with psychiatric
diagnostic instruments.
2. the assumption that 'poorly controlled psychiatric illness may compromise
adherence....' is not supported in the literature and perpetuates a myth that
psychiatrically ill people are not compliant with medications and therefore should
not be offered antiveral therapy. also a large US Veteran Affairs study found no
significant decrease among mild and moderate alcohol drinkers (but did in heavy
drinkers) in SVR. Similarly Sylvestre found no significant decrease in SVR for
intermittant IV drug users.
3. there are certain references that have not been included- Pariate studies- see
Lancet 1999 among others, the Sylvestre study, the first prospective study of
interferon induced depression by Hauser in the journal molecular psychiatry
(2002), the US Veteran Affairs study that examined the effects of alcohol use on
SVR in Veterans with HCV, studies of people with stable psychiatric illness who
received antiviral therapy among others.
4. there is an implication that escitalopram is the antidepressant of choice for
treatment of interferon-induced depression, which may be an artifact of phrama
sponsored trials. generally SSRIs as a class and one could extrapolate that most
antidepressants are efficacious in treating interferon-induced depression and that
selection of an antidepressant may be guided by side effects profiles and DDI
with DAA.
Discretionary Revisions-
1.consider another word for 'backbone' of HCV therapy.
2. expand on DDI between DAA and lamotrigine as severe rash is a side effect of
DAAs and lamotrigine is associated with rash and in particular Steven's Johnson
syndrome
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant