Transcript Effective promotion to GPs: What is good? What can be

Antidepressant drugs
for children and
teenagers:
benefits are too small to
justify the harms
Dr Peter R Mansfield
Healthy Skepticism
[email protected]
Topics
1.
2.
3.
4.
5.
6.
Introduction to Healthy Skepticism
Are we treating the cause?
Our BMJ paper
The Lancet paper
Criticism of us from Pfizer
Treatment of Adolescents with Depression Study
(TADS)
7. Why do many doctors believe that antidepressant
drugs work?
1. Introduction to
Healthy Skepticism Inc
Aim:
Improving health
by reducing harm
from misleading
drug promotion
www.healthyskepticism.org
The choice: Believe what suits you
or face the evidence
Our main messages
1. Doctors are human
2. Drug companies are profit seeking
companies
3. We have a system problem
4. People are harmed
So
We need to improve the system
Our recent publications
• Rogers WA, Mansfield PR, Braunack-Mayer AJ, Jureidini JN. The
ethics of pharmaceutical industry relationships with medical students.
Med J Aust. 2004 Apr 19;180(8):411-4.
• Mansfield P, Henry D, Tonkin A. Single-enantiomer drugs: elegant
science, disappointing effects. Clin Pharmacokinet. 2004;43(5):287-90.
• Jureidini JN, Doecke CJ, Mansfield PR, Haby MM, Menkes DB, Tonkin
AL. Efficacy and safety of antidepressants for children and
adolescents. BMJ 2004;328:879-83
• Svensson S, Mansfield PR. Escitalopram: superior to citalopram or a
chiral chimera? Psychother Psychosom. 2004 Jan-Feb;73(1):10-6.
• Mansfield PR. Healthy Skepticism’s new AdWatch: understanding drug
promotion. Med J Aust 2003; 179 (11/12): 644-645
• Jureidini J, Mansfield P, Menkes D. The statin wars. Lancet 2003 Nov
29; 362(9395)1854
• Katz D, Mansfield P, Goodman R, Tiefer L, Merz J. Psychological
aspects of gifts from drug companies. JAMA. 2003 Nov
12;290(18):2404-5
2. Are we treating the causes?
• Brain chemicals (neurotransmitters)
• Habits of thought
• Vicious cycles of negative thoughts and
feelings
• Losses
• Relationship problems
• Competitive individualism vs groups for
good causes
3. Our BMJ paper
1. Dr Jon Jureidini, child psychiatrist, Head of Psychological
Medicine, Women’s and Children’s Hospital, Adelaide
2. A/Prof Chris Doecke, pharmacist, Quality Use of Medicines
and Pharmacy Research Centre, University of South Australia
and Head of Pharmacy, Royal Adelaide Hospital
3. Dr Peter Mansfield, general practitioner, Dept of GP,
University of Adeliade
4. Dr Michelle Haby, senior epidemiologist, Department of
Human Services, Melbourne
5. Prof David Menkes, psychiatrist, University of Wales
Academic Unit, UK
6. A/Prof Ann Tonkin, clinical pharmacologist, Dept of
Pharmacology, University of Adelaide
Our conclusions
1. Benefits of antidepressants are small. We
estimated a 3 to 4 point difference on a scale
that ranges from 17 to 113.
(95% confidence 1 to 8 points)
2. Adverse effects common and sometimes
severe.
3. “The magnitude of benefit is unlikely to be
sufficient to justify risking those harms”
4. Benefits have been overstated and adverse
effects understated.
4. The Lancet paper
1.
2.
3.
4.
5.
6.
Dr Craig J Whittington PhD a
Dr Tim Kendall MRCPsych b
Prof Peter Fonagy PhD a
Prof David Cottrell MRCPsych c
Dr Andrew Cotgrove MRCPsych d
Ellen Boddington MSc a
a
Centre for Outcomes Research and Effectiveness,
Subdepartment of Clinical Health Psychology, University
College London
b Royal College of Psychiatrists’ Research Unit, London
c Academic Unit of Child and Adolescent Mental Health,
University of Leeds,
d Pine Lodge Young People's Centre, Chester, UK
The Lancet paper’s conclusions
• “Published data suggest a favourable risk-benefit
profile for some SSRIs; however, addition of
unpublished data indicates that risks could outweigh
benefits of these drugs (except fluoxetine) to treat
depression in children and young people.”
• “Non-publication of trials, for whatever reason, or
the omission of important data from published trials,
can lead to erroneous recommendations for
treatment.”
•
Whittington CJ, Kendall T, Fonagy P, Cottrell D, Cotgrove A, Boddington. Selective serotonin
reuptake inhibitors in childhood depression: systematic review of published versus
unpublished data. Lancet. 2004 Apr 24;363(9418):1341-5.
Our assessment of the Lancet paper
• We agree except:
there is no adequate justification for thinking
fluoxetine (Prozac) is any better than the other
SSRIs.
• They did not look as closely at the flaws in the
evidence for efficacy.
• There is less evidence about adverse effects
but that is not proof of greater safety.
• The onus of proof is on Lilly.
5. Criticism of us from Pfizer
• Didn’t use standard quality assessment tools
True, but they miss the problems we detected
• Didn’t criticize CBT studies
True, but our focus was on the drug studies
• Our statement re failure to disclose suicidal
activity is not true for one published study.
But it was a general statement about drug
companies not specific studies
More criticism of us from Pfizer
• Denied over- and under-statement
But the authors did claim “the results reported here
support the conclusion that sertraline is an effective,
safe, and well- tolerated treatment for children and
adolescents with MDD ”
• Claimed 10% additional benefit is worthwhile
We used more data and estimated a 3 to 4 point
difference on a scale that ranges from 17 to 113.
(95% CI 1-8)
“The magnitude of benefit is unlikely to be sufficient to
justify risking those harms”
6. Treatment of Adolescents with
Depression Study (TADS)
• Comparisons with CBT not as rigorous as the
comparison of fluoxetine vs placebo. (doubleblind, placebo-controlled)
• Fluoxetine was no significantly more effective
than placebo but there were significantly more
psychiatric adverse events with fluoxetine.*
• The authors did not report either finding in the
abstract.
• Our conclusion: “The magnitude of benefit is
unlikely to be sufficient to justify risking those
harms”
*Fluoxetine 20/109 vs placebo 9/112 Chi2 p=0.047
7. Why do many doctors believe that
antidepressant drugs work well?
A. Clinical experience:
I prescribe the drug.
The child/teenager gets better.
I conclude the drug works.
B. Wishful thinking:
Hope for clinically worthwhile advantages.
+ Ambiguity about efficacy only detectable
with a statistical microscope.
= Illusion of potency.
Post hoc ergo propter hoc fallacy
(After that therefore because of that)
“Another line consists in representing as
causes things which are not causes, on the
ground that they happened along with or
before the event in question. They assume that,
because B happens after A, it happens because
of A. Politicians are especially fond of taking
this line. Thus Demades said that the policy of
Demosthenes was the cause of all the mischief,
‘for after it the war occurred.’ ”
- Aristotle. Rhetoric. 350 BCE
Other causes
• Improvement that would have happened
anyway.
• Regression to the mean. (If something
fluctuates and you catch it at an extreme it will
usually be closer to the middle next time.)
• Non-drug effects of the medical encounter.
• A reason for believing that things will get
better.
• The placebo effect.