Healy looking for the antidote

[Guest guest]

http://www.drogue-danger-debat.org/images/david-healy.jpg

> > > >

> > > >

> > > > Professor Healy advises the MHRA that Prozac leads to

> > > > testicular shrinkage of approximately 25%.

> > > >

> > > >

> > > > Can be found at

> > > >

> > > >

> > > > http://www.socialaudit.org.uk/58096-DH%20to%20WARK.htm

> > > >

> > > >

> > > > section headed -

> > > >

> > > > Prozac and SSRIs for Children

> > > >

> > > >

> > > >

> > > >

> > > >

> > > > Prozac and SSRIs for Children

> > > >

> > > > Since I attended the SSRI review committee, the question of

> the

> > use

> > > > of Prozac in children has come to the fore. Prozac is

> apparently

> > > > under review for children by MHRA at present and the

impression

> > > > stemming from correspondence that is in the public domain

from

> > > Lilly

> > > > and from other regulators in Europe is that approval by MHRA

is

> > > > interestingly all but certain.

> > > >

> > > > I have had a chance to review a good deal of data on Prozac

> > given

> > > to

> > > > children and wish to make the following comments to the

> > committee,

> > > > many of which will not come as any surprise to you.

> > > >

> > > > There have been four trials of Prozac in children who are

> > > depressed.

> > > > The first by Simeon et al 1990 showed no differentiation

> between

> > > > Prozac and placebo.

> > > >

> > > > The second by Emslie published in 1997 showed no

> differentiation

> > > > between Prozac and placebo on the primary outcome measure of

> the

> > > > study. This was a trial in which less than 100 children were

> > > > selected from over 500 children screened. This trial also

used

> a

> > > > placebo washout period to exclude placebo responders.

> > > >

> > > > The third trial was a most unusual trial. Emslie was again

the

> > > first

> > > > author, and this trial was published in 2002. In addition to

> > > > extensive screening to select patients likely to be

responsive

> to

> > > > treatment, this trial had a placebo washout phase to exclude

> > > placebo

> > > > responders, as had the previous Prozac trials, but in

addition

> it

> > > > had a further phase, which involved children randomised into

> > Prozac

> > > > arm of the trial being given a week of Prozac 10mg first

with

> an

> > > > exclusion option for any children who appeared to respond

> > adversely

> > > > to Prozac. The trial proper started after this extraordinary

> > > > manoeuvre.

> > > >

> > > > Even with this extraordinary step on the primary outcome

> measure

> > in

> > > > the trial as indicated in FDA medical reviews of all of

these

> > > trials

> > > > Prozac did not differentiate from placebo.

> > > >

> > > > The fourth trial you'll be aware of has recently been

> published

> > in

> > > > JAMA with March as a first author, having first

featured

> in

> > > the

> > > > New York Times and elsewhere extolling the virtues of

Prozac. I

> > > > think rarely will the abstract of a major paper have been so

> at

> > > odds

> > > > with the underlying raw data.

> > > >

> > > > I understand some of you in MHRA were watching the feed from

> the

> > > FDA

> > > > paediatric advisory committee meeting. If that is the case

> > > > presumably you will have seen Dr March present the data

there

> and

> > > > heard him questioned. One of the most striking features of

this

> > > > interchange was that Dr March was forced to admit that

> according

> > to

> > > > strict FDA criteria that Prozac in his trial had not been

> shown

> > to

> > > > work either.

> > > >

> > > > The March group had manipulated the data in an interesting

> > fashion,

> > > > which involved searching for responders and non-responders

on

> > > scales

> > > > such as the CDRS or the clinical global impression scales,

and

> > > > compared these. When this is done, the effect is to squeeze

> > > patients

> > > > into categories and under those circumstances Prozac can be

> > shown

> > > to

> > > > be different from placebo but this squeezes the middle of the

> > > > clinical population in a manner that is methodologically

> > > > inappropriate. When the CDRS or other scales are used on a

> > > > continuous variable basis, as per FDA requirements for

> > > demonstrating

> > > > efficacy, the differences between Prozac and placebo are not

> > > > statistically significant. This point was recently brought

out

> > in a

> > > > position piece by Newman in the NEJM.

> > > >

> > > > You will no doubt also be aware that the rate of suicidal

acts

> on

> > > > Prozac in this latter trial is no less than the rate of

> suicidal

> > > > acts on other SSRIs, and is in fact substantially greater

than

> in

> > > > most other SSRI trials.

> > > >

> > > > It would seem therefore that there is no more evidence of

> > efficacy

> > > > or for safety on Prozac than there is for other SSRIs, and

> just

> > as

> > > > much evidence for harm.

> > > >

> > > > However it is also worth noting that there is some evidence

for

> > > > efficacy for Prozac, Seroxat/Paxil and Zoloft/Lustral for

OCD,

> > but

> > > > at present it is difficult for any clinician to use an SSRI

> for

> > any

> > > > child or teenager in the UK, owing to MHRA's handling of the

> > issues

> > > > thus far.

> > > >

> > > > For the record it's perhaps worth adding at this point that

I

> > don't

> > > > agree that MHRA made the correct move in contraindicating

> SSRIs

> > in

> > > > children. There is some evidence from trials in OCD and other

> > > > anxiety disorders that some of these drugs can be effective.

> The

> > > key

> > > > issue is that the treatment should come with the proper

> warnings

> > > for

> > > > both adult and paediatric populations.

> > > >

> > > > My suspicion is that, as MHRA rarely if ever do anything

> without

> > > > some consultation with the market authorisation holders, it

> > > appeared

> > > > to be a better bet to the market authorisation holders to

have

> > the

> > > > drugs contraindicated in children, given that so few

children

> in

> > > the

> > > > UK were having these drugs, rather than to have appropriate

> > > warnings

> > > > placed on the treatment, as such warnings might impact on

the

> > adult

> > > > market. But contra-indicating SSRIs and other

antidepressants

> is

> > > the

> > > > move that seems to have set up the current quandary MHRA are

> in,

> > > > which appears to have all but required a licensing of Prozac

> for

> > > > children.

> > > >

> > > > If Prozac is licensed for children, it is also worth noting

> that

> > > > there are other features of Prozac use in children that are

of

> > > > concern. The FDA reviews of this drug make it clear that

> children

> > > > taking Prozac failed to grow at the rate that children taking

> > > > placebo grew. The FDA asked Lilly to undertake follow-up

> studies

> > of

> > > > this effect, but as far as I know the company have not done

> so.

> > No

> > > > doubt MHRA will have noticed this problem in the trial data

> > also.

> > > If

> > > > you do intend to license Prozac, it would be good to know

that

> > the

> > > > issue of growth has been investigated properly.

> > > >

> > > > There is a further potential hazard of Prozac that FDA could

> not

> > > > have been aware of when they reviewed the drug, but which

MHRA

> > have

> > > > a chance to familiarise themselves with. In April of this

year

> > the

> > > > US Department of Health and Human Services, National

Toxicology

> > > > Programme, issued a Centre for the Evaluation of Risks to

Human

> > > > Reproduction Report that focused on Fluoxetine – NTP CERHR

> Expert

> > > > Panel Report on the reproductive and developmental toxicity

of

> > > > Fluoxetine. In this it is made clear that in male animals

> tested

> > > > Prozac leads to testicular shrinkage of approximately 25%.

The

> > use

> > > > of this drug in men generally must therefore be of some

> concern.

> > > The

> > > > use of this drug in pubertal boys would seem distinctly

> > > problematic.

[Guest guest]

http://www.drogue-danger-debat.org/images/david-healy.jpg

> > > >

> > > >

> > > > Professor Healy advises the MHRA that Prozac leads to

> > > > testicular shrinkage of approximately 25%.

> > > >

> > > >

> > > > Can be found at

> > > >

> > > >

> > > > http://www.socialaudit.org.uk/58096-DH%20to%20WARK.htm

> > > >

> > > >

> > > > section headed -

> > > >

> > > > Prozac and SSRIs for Children

> > > >

> > > >

> > > >

> > > >

> > > >

> > > > Prozac and SSRIs for Children

> > > >

> > > > Since I attended the SSRI review committee, the question of

> the

> > use

> > > > of Prozac in children has come to the fore. Prozac is

> apparently

> > > > under review for children by MHRA at present and the

impression

> > > > stemming from correspondence that is in the public domain

from

> > > Lilly

> > > > and from other regulators in Europe is that approval by MHRA

is

> > > > interestingly all but certain.

> > > >

> > > > I have had a chance to review a good deal of data on Prozac

> > given

> > > to

> > > > children and wish to make the following comments to the

> > committee,

> > > > many of which will not come as any surprise to you.

> > > >

> > > > There have been four trials of Prozac in children who are

> > > depressed.

> > > > The first by Simeon et al 1990 showed no differentiation

> between

> > > > Prozac and placebo.

> > > >

> > > > The second by Emslie published in 1997 showed no

> differentiation

> > > > between Prozac and placebo on the primary outcome measure of

> the

> > > > study. This was a trial in which less than 100 children were

> > > > selected from over 500 children screened. This trial also

used

> a

> > > > placebo washout period to exclude placebo responders.

> > > >

> > > > The third trial was a most unusual trial. Emslie was again

the

> > > first

> > > > author, and this trial was published in 2002. In addition to

> > > > extensive screening to select patients likely to be

responsive

> to

> > > > treatment, this trial had a placebo washout phase to exclude

> > > placebo

> > > > responders, as had the previous Prozac trials, but in

addition

> it

> > > > had a further phase, which involved children randomised into

> > Prozac

> > > > arm of the trial being given a week of Prozac 10mg first

with

> an

> > > > exclusion option for any children who appeared to respond

> > adversely

> > > > to Prozac. The trial proper started after this extraordinary

> > > > manoeuvre.

> > > >

> > > > Even with this extraordinary step on the primary outcome

> measure

> > in

> > > > the trial as indicated in FDA medical reviews of all of

these

> > > trials

> > > > Prozac did not differentiate from placebo.

> > > >

> > > > The fourth trial you'll be aware of has recently been

> published

> > in

> > > > JAMA with March as a first author, having first

featured

> in

> > > the

> > > > New York Times and elsewhere extolling the virtues of

Prozac. I

> > > > think rarely will the abstract of a major paper have been so

> at

> > > odds

> > > > with the underlying raw data.

> > > >

> > > > I understand some of you in MHRA were watching the feed from

> the

> > > FDA

> > > > paediatric advisory committee meeting. If that is the case

> > > > presumably you will have seen Dr March present the data

there

> and

> > > > heard him questioned. One of the most striking features of

this

> > > > interchange was that Dr March was forced to admit that

> according

> > to

> > > > strict FDA criteria that Prozac in his trial had not been

> shown

> > to

> > > > work either.

> > > >

> > > > The March group had manipulated the data in an interesting

> > fashion,

> > > > which involved searching for responders and non-responders

on

> > > scales

> > > > such as the CDRS or the clinical global impression scales,

and

> > > > compared these. When this is done, the effect is to squeeze

> > > patients

> > > > into categories and under those circumstances Prozac can be

> > shown

> > > to

> > > > be different from placebo but this squeezes the middle of the

> > > > clinical population in a manner that is methodologically

> > > > inappropriate. When the CDRS or other scales are used on a

> > > > continuous variable basis, as per FDA requirements for

> > > demonstrating

> > > > efficacy, the differences between Prozac and placebo are not

> > > > statistically significant. This point was recently brought

out

> > in a

> > > > position piece by Newman in the NEJM.

> > > >

> > > > You will no doubt also be aware that the rate of suicidal

acts

> on

> > > > Prozac in this latter trial is no less than the rate of

> suicidal

> > > > acts on other SSRIs, and is in fact substantially greater

than

> in

> > > > most other SSRI trials.

> > > >

> > > > It would seem therefore that there is no more evidence of

> > efficacy

> > > > or for safety on Prozac than there is for other SSRIs, and

> just

> > as

> > > > much evidence for harm.

> > > >

> > > > However it is also worth noting that there is some evidence

for

> > > > efficacy for Prozac, Seroxat/Paxil and Zoloft/Lustral for

OCD,

> > but

> > > > at present it is difficult for any clinician to use an SSRI

> for

> > any

> > > > child or teenager in the UK, owing to MHRA's handling of the

> > issues

> > > > thus far.

> > > >

> > > > For the record it's perhaps worth adding at this point that

I

> > don't

> > > > agree that MHRA made the correct move in contraindicating

> SSRIs

> > in

> > > > children. There is some evidence from trials in OCD and other

> > > > anxiety disorders that some of these drugs can be effective.

> The

> > > key

> > > > issue is that the treatment should come with the proper

> warnings

> > > for

> > > > both adult and paediatric populations.

> > > >

> > > > My suspicion is that, as MHRA rarely if ever do anything

> without

> > > > some consultation with the market authorisation holders, it

> > > appeared

> > > > to be a better bet to the market authorisation holders to

have

> > the

> > > > drugs contraindicated in children, given that so few

children

> in

> > > the

> > > > UK were having these drugs, rather than to have appropriate

> > > warnings

> > > > placed on the treatment, as such warnings might impact on

the

> > adult

> > > > market. But contra-indicating SSRIs and other

antidepressants

> is

> > > the

> > > > move that seems to have set up the current quandary MHRA are

> in,

> > > > which appears to have all but required a licensing of Prozac

> for

> > > > children.

> > > >

> > > > If Prozac is licensed for children, it is also worth noting

> that

> > > > there are other features of Prozac use in children that are

of

> > > > concern. The FDA reviews of this drug make it clear that

> children

> > > > taking Prozac failed to grow at the rate that children taking

> > > > placebo grew. The FDA asked Lilly to undertake follow-up

> studies

> > of

> > > > this effect, but as far as I know the company have not done

> so.

> > No

> > > > doubt MHRA will have noticed this problem in the trial data

> > also.

> > > If

> > > > you do intend to license Prozac, it would be good to know

that

> > the

> > > > issue of growth has been investigated properly.

> > > >

> > > > There is a further potential hazard of Prozac that FDA could

> not

> > > > have been aware of when they reviewed the drug, but which

MHRA

> > have

> > > > a chance to familiarise themselves with. In April of this

year

> > the

> > > > US Department of Health and Human Services, National

Toxicology

> > > > Programme, issued a Centre for the Evaluation of Risks to

Human

> > > > Reproduction Report that focused on Fluoxetine – NTP CERHR

> Expert

> > > > Panel Report on the reproductive and developmental toxicity

of

> > > > Fluoxetine. In this it is made clear that in male animals

> tested

> > > > Prozac leads to testicular shrinkage of approximately 25%.

The

> > use

> > > > of this drug in men generally must therefore be of some

> concern.

> > > The

> > > > use of this drug in pubertal boys would seem distinctly

> > > problematic.