Antipsychotics
in schizophrenia: a message from CATIE
Independent
prescribing for pharmacists and nurses
Are
you suffering from information overload?
The
results of the first two phases of the Clinical
Antipsychotic Trials of Intervention Effectiveness
(CATIE) schizophrenia study provide a useful
insight into the effectiveness of antipsychotics.1–3
This
publicly funded, double-blind, US study
included a broad population of patients
(n=1493) with chronic schizophrenia. It
had minimal exclusion criteria and allowed
co-existing conditions and use of other
medications. In phase 1, patients were randomly
allocated to treatment with olanzapine,
quetiapine, risperidone, ziprasidone (not
available in the UK) or the typical antipsychotic,
perphenazine for up to 18 months.1
Doses were adjusted within a defined range
according to clinical judgment. Those receiving
an atypical antipsychotic who discontinued
treatment could be randomised to an alternative
atypical in phase 2. This had two arms:
A: ziprasidone vs. olanzapine, quetiapine,
or risperidone;2
or B: clozapine (open-label) vs. olanzapine,
quetiapine, or risperidone.3
The primary outcome in all phases was time
to discontinuation for any reason, an important
clinical endpoint that reflects both clinician
and patient judgements about efficacy and
tolerability.
Only
26% of patients (range 18–36%) completed
the study on their first assigned antipsychotic
in phase 1: 10–19% of patients discontinued
treatment because of intolerable side effects,
15–28% for lack of efficacy, and 24–34%
for other reasons. The time to discontinuation
for any reason was significantly longer
for olanzapine than for risperidone or quetiapine,
but not for perphenazine or ziprasidone
(see Table). Compared with
other treatments, olanzapine was associated
with the lowest rate of discontinuations
for efficacy reasons (15% vs. 24–28%),
but the highest rate due to side effects
(19% vs. 10–16%), notably weight gain
or metabolic effects (9% vs. 1–4%,
P<0.001). More patients discontinued
perphenazine due to extrapyramidal effects
(8% vs. 2–4 %, P=0.002), and more
patients discontinued quetiapine for anticholinergic
side effects (31% vs. 20–25%, P<0.001).
In phase 2, many patients who discontinued
their assigned atypical were able to successfully
complete the study on an alternative (see
Table). In phase 2A, the
times to discontinuation for patients switched
to risperidone or olanzapine were significantly
longer than for those switched to quetiapine
or ziprasidone. Clozapine appeared more
effective than the other atypical antipsychotics
in phase 2B. However, the low number of
patients in this phase questions the validity
of this finding.
The CATIE study suggests
that there is little to choose in terms
of overall effectiveness between the antipsychotics
studied, including the typical antipsychotic,
perphenazine. All were associated with high
rates of intolerable side effects and failure
to control symptoms. Within the limited
range of effectiveness, and excluding clozapine
(which requires careful safety monitoring),4
olanzapine appeared the most effective of
the other atypical agents, although its
benefits were limited by unacceptable weight
gain and metabolic effects. It should be
noted that the olanzapine doses used in
CATIE were high (see Table)
relative to the UK licensed dose range of
5–20mg daily, which may limit the
relevance of these findings to UK clinical
practice.
The CATIE study clearly
identifies the need for individualised antipsychotic
treatment for patients with schizophrenia.
Doctors and patients should carefully evaluate
the trade-offs between efficacy and side
effects, to choose the antipsychotic (atypical
or typical) that is most likely to be acceptable.
No one antipsychotic is suitable for everyone.
- Lieberman JA, Stroup TS, McEvoy JP, et
al. New Engl J Med 2005;353:1209–23
- Stroup
TS, Lieberman JA, McEvoy JP, et al. Am
J Psychiatry 2006;163:611–22
- McEvoy
JP, Lieberman JA, Stroup TS, et al. Am
J Psychiatry 2006;163:600–10
- Clozaril:
Summary of Product Characteristics. Accessed
from www.medicines.org.uk
on 27/06/06
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On 1st May, regulations
were changed to allow independent prescribing
by pharmacists and nurses. The Department
of Health (DH) defines independent prescribing
as prescribing by a practitioner (e.g. doctor,
dentist, nurse, pharmacist) responsible
and accountable for the assessment of patients
with undiagnosed or diagnosed conditions,
and for decisions about the clinical management
required, including prescribing.1
Once qualified, Pharmacist
Independent Prescribers will be able to
prescribe any licensed medicine for any
medical condition, with the exception of
controlled drugs (until appropriate changes
are made to the Misuse of Drugs regulations).1
Independent prescribers must accept full
professional, clinical and medico-legal
responsibility for their prescribing decisions.
They should, therefore, only prescribe within
their own experience, in situations where
they feel fully competent, using medicines
that they feel are effective for the patient
and the condition being treated.2
The Extended Nurse Prescribers
Formulary has been discontinued,3
and qualified Extended Formulary Nurse Prescribers
are now known as Nurse Independent Prescribers,
and can prescribe any licensed medicine
for any medical condition within their competence,
including some controlled drugs.1
Community Practitioner Nurse Prescribers
will still only be entitled to prescribe
from the Nurse Prescribers' Formulary for
Community Practitioners.4
Pharmacists and nurses will
continue to be able to train and act as
supplementary prescribers.4
In some settings, this will be the best
option because it enables nurses and pharmacists
to prescribe the same medicines as an NHS
doctor, including all controlled drugs and
unlicensed medicines, provided they are
stipulated in the patient's clinical management
plan.2
Many nurses already have a dual independent-
supplementary prescribing qualification.4
Training requirements for
Pharmacist Independent Prescribers are being
worked on,2
and the outline curriculum is expected later
this year. Employing organisations will
select eligible pharmacists to train according
to local service and patient needs. Central
funding will be available for those working
for the NHS, including community pharmacists
who supply services to NHS organisations.1
Non-NHS pharmacists will need a source of
funding for their training, a medical supervisor
to help with the ‘supervision in practice’
element of the course, and access to a prescribing
budget once qualified.2
- Department of Health.
Improving patients' access to medicines:
a guide to implementing nurse and pharmacist
independent prescribing within the NHS
in England. April 2006. Accessed from
www.dh.gov.uk
on 26/06/2006
- Department of Health.
Pharmacist independent prescribing FAQ.
May 2006. Accessed from www.dh.gov.uk
on 26/06/2006
- Department of Health.
Nurse prescribing FAQ. May 2006. Accessed
from www.dh.gov.uk
on 26/06/2006
- Pharmaceutical Services
Negotiating Committee. Pharmacist and
nurse independent prescribing. Accessed
from www.psnc.org.uk
on 19/05/2006
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The sheer volume of information
being continually generated about different
interventions makes it very difficult for
healthcare professionals to keep up to date.
Trying to keep up to date by reading primary
research in journals is impossible. You
can miss key evidence relevant to your practice,
and what you do manage to read may not be
a true portrayal of the evidence base. Abstracts
can contain information not consistent with
the full article,1
and meeting abstracts or posters from conferences
are particularly problematic in not giving
the full picture.2
A better way to keep up to date is to read
summaries of evidence from reputable sources.
These include NICE, The Cochrane Library,
Clinical Evidence, InfoPoems, MeReC, Drug
and Therapeutics Bulletin and PRODIGY.
This topic is discussed
in more detail in MeReC Briefing
No. 30, Using evidence to guide practice
(September 2005) and the related supplement
(www.npc.co.uk/MeReC_Briefings/briefing2004.htm).
To complement MeReC
Bulletins and Extras, we have
recently introduced a new electronic publication,
MeReC Rapid Review. In this, we
quickly appraise key new trials or guidance
and set them into the context of the current
evidence base and healthcare practice. The
first two editions are available on the
NPC website at www.npc.co.uk/merec_rapid_review.htm.
To ensure you continue to
be aware of all MeReC support available
to you, please register to receive an email
alert when a new MeReC resource is added
to the NPC website. Register at
www.npc.co.uk/merec.htm.
- Pitkin RM,Branagan MA,
Burmeister LF. Accuracy of data in abstracts
of published research articles. JAMA 1999;281:1110–11
- Toma M, McAlister FA,
Bialy L, et al. Transition from meeting
abstract to full-length journal article
for randomised controlled trials. JAMA
2006;295:1281–87
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The National
Institute for Health and Clinical Excellence
(NICE) is associated with MeReC Publications
published by the NPC through a funding contract.
This arrangement provides NICE with the
ability to secure value for money in the
use of NHS funds invested in its work and
enables it to influence topic selection,
methodology and dissemination practice.
NICE considers the work of this organisation
to be of value to the NHS in England and
Wales and recommends that it be used to
inform decisions on service organisation
and delivery. This publication represents
the views of the authors and not necessarily
those of the Institute.
©National
Prescribing Centre 2006, The Infirmary,
70 Pembroke Place, Liverpool, L69 3GF
Telephone: 0151 794 8146 Fax: 0151 794 8139
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