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Jonathan Bland is a hospital clinical pharmacist
from Lincolnshire
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Atypical antipsychotics have been one of the most significant advances
in psychiatric medicine over the last few years and have been widely
welcomed by both health professionals and service users alike. Readers
unfamiliar with the phrase “atypical antipsychotic” might
well ask what it means. In fact, there is no specific medical definition
for an atypical antipsychotic. Rather, it has come to signify, to clinicians
at least, an antipsychotic with a lower propensity for causing extrapyramidal
side effects (EPSEs) — movement disorder side effects that include
dystonia, akathisia, parkinsonian symptoms and tardive dyskinesia. EPSEs
can be frequently caused by the so called “typical” antipsychotics
such as haloperidol. The development therefore of the new generation
of atypical antipsychotics with this lower propensity for causing EPSEs
has been of tremendous benefit to sufferers of mental illnesses such
as schizophrenia.
Atypical antipsychotics are now marketed by a number of pharmaceutical
companies and they have become a huge commercial success. The combined
global sales for 2004 for the three atypical drugs olanzapine, risperidone
and quetiapine totalled over $9bn.
Atypical antipsychotics are acknowledged and recognised internationally
now, and in England and Wales are highlighted specifically by National
Institute for Clinical Excellence guidance publications and in the British
National Formulary. This has been an interesting development, given the
fact that the “atypical” concept is as much about an improved
EPSE profile as it is about substantial improvement in the treatment
of schizophrenia compared with typical antipsychotics. Individually the
atypicals are as different from each other in many ways as they differ
from the typicals. There are differences in chemical structure, pharmacology
and side effect
profile. For example, some atypicals cause no elevation in prolactin;
with others, hyperprolactinaemia can be a significant problem.
Given that the concept of atypicality is not an exact science, it is
interesting to note the distinct categorisation of antipsychotics now
as being either “typical” or “atypical”. What
qualifies a drug to become a member of this “atypical” club?
Sulpiride, for example, is not too dissimilar, either structurally or
pharmacologically, from amisulpride (both are substituted benzamides),
yet although amisulpride is classed as an atypical, sulpiride is not.
An interesting fact about most of the marketed atypicals and their clinical
trial data was that the typical antipsychotic most frequently used as
comparator was haloperidol. Haloperidol has a pronounced EPSE profile,
so it was hardly surprising that the trial atypicals had an improved
EPSE profile in comparison.
The concept of atypicality for a number of atypical drugs needs to be
qualified with the fact that at higher dosages there is an increased
risk of EPSE: in other words, a potential for some atypicals to lose
their atypicality. It is to be hoped that all clinicians using these
drugs are aware of this, otherwise premium prices are being paid, possibly
for no extra benefit than could have been achieved using a typical agent
at a fraction of the cost.
When looking at the clinical trials for all the atypicals, a consistent
feature is the use made in every trial of psychiatric rating scales to
measure both efficacy/outcomes of treatment and EPSEs. Outcome assessment
scales commonly used include the Positive and Negative Syndrome Scale
(PANSS), the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global
Impression scale (CGI). Side effect rating scales used include the Barnes
Akathisia Rating Scale (BARS), the Simpson-Angus Scale (SAS) used to
measure parkinsonian symptoms and the Abnormal Involuntary Movement Scale
(AIMS) which is used to detect tardive dyskinesia.
In all the atypical clinical trials the pharmaceutical companies attach
a huge amount of importance to the statistical analysis of the rating
scale results. This is not surprising because these results form the
backbone of the subsequent licensing and marketing of the atypical drug.
It would seem logical and good clinical practice, therefore, for rating
scales to be used routinely in the real-life situation, both at baseline
before initiating the atypical and while on therapy. But does this happen?
Although quite rightly a principle reason behind the development of the
atypical antipsychotics has been to reduce the neurological side effect
burden on patients, the physical health of the individual is just as
important. Specialisation is the current buzzword in clinical pharmacy,
but patients do not exist as specialties but as complete human beings
and as such have to be treated holistically. For example, a specific
side effect associated with a number of the atypicals is significant
weight gain, which could have the potential to predispose the individual
to impaired glucose tolerance or even type 2 diabetes. The consequences
of not fully addressing the physical health needs of individuals suffering
from mental illness, including those being treated with atypicals, cannot
be overstated.
The language that is used in articles written about typical and atypical
antipsychotics certainly warrants examination. When typical agents are
being discussed the word “typical” is frequently prefixed
with the adjectives “old” and “cheap”, setting
the tone for couching the typicals in a derogatory light. Apart from
these words being irrelevant and unscientific you rarely see them used
in the context of drugs for physical conditions, eg, digoxin, being described
as “old” or “cheap”. The point is that all antipsychotics,
whether they are typical or atypical, should stand or fall on their own
merits. High premium prices for drugs do not, and never will, automatically
confer benefits for all patients.
There is a certain irony as a result of the proliferation of atypical
antipsychotics in that it could potentially affect the outcome of treatment-resistant
schizophrenia. NICE has recommended that clozapine (which has proven
efficacy in this condition) should be introduced if treatment with at
least two antipsychotics (at least one of which should be an atypical),
each for at least six to eight weeks, has resulted in a lack of satisfactory
clinical improvement. But the potential now exists with numerous atypicals
on the market for clozapine to be used later rather than sooner, which
could be to the ultimate detriment of the patient.
In some quarters the typical antipsychotics have already been consigned
to the pharmaceutical dustbin. But it is worth noting the NICE guidance
on atypicals, which states that where a typical agent is controlling
symptoms without undue side effects then changing to an atypical agent
is not necessary.
Overall the atypical antipsychotics have been an advance as far as drug
therapy in mental illness has been concerned. What all health professionals
responsible for patients with a mental illness taking these expensive
drugs need to do is ensure that in every case the client gets the benefit
of treatment from the atypical as well as a minimum amount of EPSEs.
This may then help justify the potential 20- to 30-fold increase in drugs
costs as a result of not using “older” and “cheaper” drugs
like haloperidol or chlorpromazine. |
The
Pharmaceutical Journal