892
6 Ciapponi A, Pizarro R, Harrison J.
Trimatazidine for stable angina
(review). The Cochrane Collaboration:
The Cochrane Library 2006; Issue 2.
7 Brottier L, Barat L, Combe C et al.
Therapeutic value of a cardio protect-
ive agent in patients with severe isch-
aemic cardiomyopathy. Eur Heart J
1990; 11: 207–12.
8 Di Napoli P, Taccardi AA, Barsotti A.
Long term cardioprotective action of
trimetazidine and potential effects on
CATIE for clinicians
The paper by Citrome and Stroup
published in this issue is a very inter-
esting contribution to the field of clin-
ical psychopharmacology (1).
First, I would like to explain the
rationale of the CATIE study (Effect-
iveness of Antipsychotic Drugs in
Patients with Chronic Schizophrenia)
(2).
Schizophrenia is the most serious
and enduring of mental illnesses but
all current treatments provide only
partial relief from symptoms. There
are now a large number of second-
generation antipsychotics which offer
many advantages but their similarities
are greater than their differences and
there is a great deal of commercially
led activity to establish advantages of
one over another. In response to this
there have been a number of inde-
pendent studies, usually in the form
of meta-analyses, that have tried to
provide an unbiased view of this field.
A good example of this is the study
by Davis et al. (3).
Schizophrenia is a disease that
attacks young people, is a relatively
untreatable condition and is of life-
long duration. Therefore pharmaceuti-
cal companies see this disease as an
important opportunity for revenue
generation. My own view is that this
is laudable if it generates more fund-
ing for schizophrenia research. How-
Journal compilation ª 2006 Blackwell Publishing Ltd Int J Clin Pract, August 2006, 60, 8, 891–895
the inflammatory process in patients
with ischaemic dilated cardiomyopa-
thy. Heart 2005; 91: 161–5.
9 Vitale C, Wajngaten M, Sposato B
et al. Trimetazidine improves left ven-
tricular function and quality of life in
elderly patients with coronary artery
disease. Eur Heart J 2004; 25: 1814–
21.
10 Fragasso G, Piatti PM, Monti L et al.
Short and long term beneficial effects
of trimetazidine in patients with dia-
ever, many pharmaceutical companies
have used very heavy-handed market-
ing strategies for their antipsychotic
products and this has created tension
generated by doctors who are sceptical
about the activities of the pharmaceu-
tical industry.
The CATIE study was conceived to
overcome this tension and to provide
a definitive view of which antipsychot-
ic might be the most useful in schizo-
phrenia.
The CATIE study is therefore an
independently funded NIH study
which compared modern second-gen-
eration antipsychotics to each other
and to a first-generation antipsychotic
perphenazine. It was a multicentre
prospective study at 57 US sites con-
ducted over an 18-month period. The
study is fully explained in the current
paper by Citrome et al. A total of
1493 patients were recruited. The
study was blind and randomised to
either olanzapine (7.5–30 mg/day),
perphenazine (8–32 mg/day), queitia-
pine (200–800 mg/day) or risperidone
(1.5–6 mg/day). Ziprasidone was
included later in the study at 40–
160 mg per day following its approval
during the course of the study by the
FDA.
The choice of dosing was interest-
ing as it was driven by manufacturer
input to the protocol. Many manufac-
EDITORIAL
betes and ischaemic cardiomyopathy.
Am Heart J 2003; 146: E1–8.
11 El-Kady T, El-Sabban K, Gabaly M
et al. Effects of Trimetazidine on
myocardial perfusion and contractile
response of electronically dysfunctional
myocardium in ischaemic cardiomyop-
athy. Am J Cardiovasc Drugs 2005; 5:
271–8.
turers are very concerned to help doc-
tors understand what may be the
optimal dose for their drug. However,
this is alluded to as a possible source
of error in the ‘Discussion’ section of
the CATIE study.
The overall conclusion of the CA-
TIE study is that olanzapine is the
most favourable drug with regard to
discontinuation rates but that it was
least favourable with regard to meta-
bolic syndromes. Phase II of the CA-
TIE study involved re-randomisation
to the same group of drugs but also
including clozapine.
One of the imponderables of CA-
TIE is that it does not have a top line
with regard to the ranking of anti-
psychotics and their relative risk–bene-
fit ratios. The Citrome paper helps in
this regard. The current paper by
Citrome et al. adds a further level of
sophistication to this work in two
ways. It therefore explains the concept
of numbers needed to treat (NNT) vs.
numbers needed to harm (NNH).
Traditional clinical pharmacologists
were trained in the concepts of thera-
peutic ratios and therapeutic indices
which were arcane and complicated
and required knowledge of logarithmic
mathematics. NNT/NNH is a much
more understandable index of efficacy
vs. safety analysis and gives us a much
more clearer view of the overall
ª 2006 The Authors
EDITORIAL
effectiveness in broad and easily under-
standable terms. This is an ideal article
for a general readership that may not
want to plough through the original
iterations of the CATIE study.
R. Kerwin
Clinical Neuropharmacology,
Institute of Psychiatry,
London, UK
PDE-5 inhibitors: spoilt for choice
The introduction of oral agents for
the treatment of erectile dysfunction
(ED) has changed the lives of many
men around the world and revolution-
ised the treatment of men with erec-
tion problems of all severities and
aetiologies. ED affects up to 50% of
men between 40 and 70 years of age,
with age being the variable most
strongly associated with ED (1).
Erectile dysfunction and coronary
artery disease overlap in risk factors,
aetiology and clinical outcomes. It has
become clear that ED is an important
marker of vascular disease throughout
the arterial tree, including coronary
artery disease, stroke and diabetes. Epi-
demiological studies have demonstrated
a close association between ED and vas-
cular disease. The shared aetiological
factor is endothelial dysfunction, which
occurs in hypertension, smoking,
abnormal lipid profiles and diabetes.
The beneficial effects of phosphodiest-
erase type 5 (PDE-5) inhibitors on
endothelial function have been the sub-
ject of much interest and debate (2).
Wright’s paper reviews the struc-
ture, selectivity, pharmacokinetics and
the onset and duration of effect of the
three agents, together with tolerability
and patient preference (3). A number
of preference studies have been con-
ducted with PDE-5 inhibitors and
they have demonstrated inconsistent
findings (4). This led to a recommen-
dation for the special design of such
trials that can minimise bias to a
ª 2006 The Authors
Journal compilation ª 2006 Blackwell Publishing Ltd Int J Clin Pract, August 2006, 60, 8, 891–895
REFERENCES
1 Citrome L, Stroup TS. Schizophrenia,
clinical antipsychotic trials of interven-
tion effectiveness and number needed
to treat: how can CATIE inform clini-
cians? Int J Clin Pract 2006; 60: 933–
40.
2 Lieberman JA, Stroup TS, Joseph P
et al. Effectiveness of antipsychotic
greater extent and provide better data
for physicians and their patients.
Sildenafil has been available on the
world market since 1998 and was
joined in 2003 by tadalafil and varde-
nafil. They are all effective, safe and
reliable oral agents. All three drugs
share the same mode of action and all
are contraindicated with nitrate medi-
cations. There are significant differ-
ences between the three agents.
Sildenafil has the longest and most
comprehensive trial experience in
patients and the most robust safety
and tolerability data, and there has
been much interest in whether or not
the two newer agents offer significant
advantages over sildenafil.
Comparing different interventions
for the same condition is problematic.
This is because large direct compari-
sons are uncommon and provide us
with only a very small proportion of
the large numbers of randomised trials
comparing different interventions with
the same or similar comparators.
Designing a trial which is randomised
and properly blinded that directly
compares one PDE-5 inhibitor with
another in a normal home setting is
fraught with problems.
Moore et al. tackled the problem
by reviewing published randomised,
double-blind trials of all oral PDE-5
inhibitors for erectile dysfunction.
There are no randomised and properly
blinded trials comparing the PDE-5
inhibitors in a home setting. Analyses
893
drugs in patients with chronic schizo-
phrenia. N Engl J Med 2005; 353:
1209–23.
3 Davis JM, Chen N, Glick ID. A meta
analysis of the efficacy of second gen-
eration antipsychotics. Arch Gen Psychi-
atry 2003; 60: 553–64.
of efficacy and harm were carried out
for each treatment and the results
compared where there was a common
comparator and consistency about
outcome reporting using equivalent
doses. It is concluded that there were
differences between the trials in out-
comes reported, limiting conclusions
and the most useful outcomes were
not reported. For common outcomes
there was similar efficacy between the
three PDE5 inhibitors (5).
In clinical practice, discontinuation
rates beyond a year are relatively high.
Factors such as spontaneity, natural-
ness, and onset and duration of action
may all influence preferences. And cer-
tainly in some studies men have shown
preferences for particular oral PDE-5
inhibitors over others. This may well be
important in determining whether or
not patients continue treatment in the
medium and long term. There is no
doubt that providing patients with full
information on the pros and cons of
treatment options can ensure that
patients are treated with a therapy that
fits more closely with their wishes, and
this will lead to continuation of therapy
for optimal efficacy (6).
At the end of the day the old saying
‘It it is not what you give, but how
you give it’ remains very important. A
dedicated, and well educated physi-
cian, who can set realistic expectations
and encourage couples to comply with
treatment, will make the true differ-
ence (7).