Content uploaded by Aliza le Roux
Author content
All content in this area was uploaded by Aliza le Roux
Content may be subject to copyright.
ORIGINAL Afr J Psychiatry 2008;11:287-290
AAffrriiccaann JJoouurrnnaall ooff PPssyycchhiiaattrryy • November 2008 228877
Introduction
Internationally, clinical practice guidelines – such as National
Institute for Clinical Excellence (NICE) guidelines1and
others2,3 – are widely available for the treatment of mental
illness. Although adherence to these guidelines varies4, their
aims are to assist in clinical decision-making and increase the
cost-effectiveness of services by reducing unnecessary
variations in prescribing practices.5In South Africa, mental
illnesses such as schizophrenia impose a heavy financial
burden on health services6, but we do not have uniform
provincial or national guidelines regulating practices in the
treatment of mental illness. We also often have a difference in
ethnic background between clinician and patient, a factor that
could lead to mistaken assumptions that affect the way in
which clinicians adhere to guidelines or make treatment
decisions.7-9 Currently, our standards are inter national
guidelines, which are not specifically adapted to local
circumstances.
The aim of this study is to examine the antipsychotic
prescription patterns for a population with schizophrenia or
schizoaffective disorder, to determine if local practices are
comparable with standard international guidelines. In order to
limit possible confounding factors an ethnically homogenous
group was chosen. We pay particular attention to clozapine
prescription as this was at the time of the study the only
second generation antipsychotic available to the public
service patient population in the Western Cape, where our
study took place. We investigated differences between three
neighbouring areas in the Western Cape, where we expected
treatments to be similar, due to the relatively homogeneous
nature of the population.
Antipsychotic prescription
patterns in Xhosa patients with
schizophrenia or schizoaffective
disorder
L Koen, P Magni, DJH Niehaus, A le Roux
Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa
Abstract
Objective: To examine the degree to which South African physicians use similar treatment guidelines in their prescription of
antipsychotic medication. Method: Data on the prescriptions for Xhosa patients with schizophrenia and schizoaffective disorder
were retrospectively examined to investigate differences between three catchment areas in the Western Cape, especially in terms
of clozapine use. Results: There was an overall low rate (10.0%) of clozapine use and a relatively high occurrence of polypharmacy
(28.6% of 510 patients). There were statistically significant differences between the three catchment areas in terms of clozapine
(p=0.002) and haloperidol (p=0.001) use. Valkenberg hospital had the highest number of clozapine prescriptions and the lowest
of haloperidol. Prescriptions of depot antipsychotics did not differ between catchment areas. Conclusion: Discrepancies in
antipsychotic medicine prescription patterns were evident between the examined hospitals. It is becoming paramount for practical
implementation of guidelines to be improved in South Africa to address, e.g., low clozapine use and the high frequency of
polypharmacy.
Keywords: Practice guidelines; Schizophrenia
Received: 03-12-2007
Accepted: 19-02-2008
Correspondence:
Dr L Koen
PO Box 19090, Tygerberg, 7505, South Africa
email: liezlk@sun.ac.za
ORIGINAL Afr J Psychiatry 2008;11:287-290
AAffrriiccaann JJoouurrnnaall ooff PPssyycchhiiaattrryy • November 2008 228888
Method
Participants
As part of a large Xhosa genetic study taking place between
2002 and 200510, 510 subjects were recruited from three
“catchment areas” in the greater metropole of Cape Town,
South Africa. These catchment areas consisted of three
hospitals – the Stikland (STH), Lentegeur (LGH) and
Valkenberg (VBH) psychiatric hospitals – and their affiliated
community healthcare clinics (CHCs). These hospitals form
part of one platform of care, namely the Associated Psychiatric
Hospitals (APH). Mental healthcare workers from each of these
centres were asked to identify all possible participants, who
were then screened for suitability based on the following
inclusion criteria: (1) diagnosis of schizophrenia or
schizoaffective disorder according to DSM-IV criteria11 and;
(2) Xhosa ethnicity (four out of four grandparents reported as
of Xhosa origin). Patients were excluded if they had a
significant general medical condition.
Data collection
For the original study10, each subject was inter viewed by a
psychiatrist or an experienced, trained research sister, using
the standardised Diagnostic Interview for Genetic Studies
version 2 (DIGS)12, as well as the Schedule for the Assessment
of Negative Symptoms (SANS)1 3 and the Schedule for the
Assessment of Positive Symptoms (SAPS).14 To ensure inter-
rater consistency over the entire period of recruitment, all
participants were assessed by both raters simultaneously
during the first year of the study. Each participant was
interviewed in their mother tongue, namely Xhosa. The study
was approved by the institutional review board of the
University of Stellenbosch (97/005).
For the purposes of this study, the DIGS and research
folders of all participants were retrospectively examined for
demographic details, type, dose and duration of antipsychotic
drug prescribed, and the catchment area in which the
participant received their treatment. Data were then compared
between the three catchment areas, focusing on differences in
antipsychotic drug prescription, SANS and SAPS scores. The
SANS and SAPS scores of patients using and not using
Clozapine were also compared.
General prescription constraints
At the time of collection of study data conventional
antipsychotics were the only first line treatment available for
prescription to public service patients throughout the Western
Cape. Clozapine was the only atypical freely available but due
to its side-effect profile is considered to be a third-line
treatment (as per international convention), only prescribed
for treatment-resistant patients or patients with prominent side-
effects on conventional antipsychotics.
Results
Demographics
The demographic structures of participants (n=510) were
similar across the three hospitals. Of 510 participants in this
study, 426 (83.5%) were male and 84 (16.5%) female. The
majority (n=403, 79.8%), had never married, 53 (10.5%) were
married, 16 (3.2%), divorced, 18 (3.6%), separated, and 15
(3.0%) were widowed (data on marital status were unavailable
for 5 participants). The mean age at interview was 35.0 years
(range = 15-70, SD = 11.0), whilst the mean age at onset of
illness was 23.3 years (range = 10-55, SD = 6.8). Three
hundred and twenty-two (63.1%) participants were receiving a
disability grant, 165 (32.3%) were unemployed, 18 (3.5%)
were employed, and 1 (0.2%) was a student (data for 4
participants were unknown).
Medication
Fifty-one (10.0%) of the 510 participants were prescribed
clozapine, on a mean dose of 318.0 mg (SD = 188.5 mg), at the
time of interview. The remaining participants were prescribed
as follows: haloperidol 209 (41.0%), chlorpromazine 89
(17.5%), and depot preparation 252 (49.4%). Fluphenazine
was the most common depot preparation prescribed (150 or
59.5% of the 252 prescriptions). Zuclopenthixol was used in 64
patients (25.4%) and Flupenthixol in the remaining 38 patients
(15.1%).
In those using one or more conventional antipsychotics, the
mean dose in chlorpromazine equivalents was 233.2 mg (SD =
220.7 mg). More than one antipsychotic drug was prescribed
to 142 (27.8%) of the patients at the time of interview. The most
frequently used combination was haloperidol and a depot
preparation (n = 77, 54.2%). Of the 51 patients prescribed
clozapine, 11 (22.0%) were also prescribed one or more
conventional antipsychotic.
Clozapine users – clinical profile
The 51 clozapine users had a mean SANS score of 9.8 (SD =
4.8), and a SAPS score of 7.46 (SD 4.4). Those patients not
using clozapine had mean scores of 8.86 (SD 4.1) for SANS
and 6.21 (SD 5.1) for SAPS. Clozapine users had significantly
higher SAPS scores than the non-clozapine users (p = 0.013)
but the SANS scores of the two groups were similar (p = 0.53).
Comparing the three catchment areas
Overall, 87 (17.1%) patients were receiving their treatment in
the STH catchment area. The VBH catchment area consisted of
183 (35.9%) patients, and the LGH catchment area of 240
(47.1%) patients. Thirty-seven (44.6%) of the STH patients
were inpatients, 65 (40.9%) of the VBH and 127 (56.7%) of the
LGH patients were inpatients. VBH therefore had a significantly
lower proportion of inpatients than LGH (p < 0.05).
For clozapine and haloperidol prescriptions, there were
significant differences between the three catchment areas
(Table I). Specifically, VBH had the highest clozapine and
Table I. Main antipsychotic drug prescriptions for Xhosa
patients with schizophrenia or schizoaffective disorder,
compared between the catchment areas for three psychiatric
hospitals in the Western Cape.
Hospital: Lentegeur Stikland Valkenberg
Clozapine*** 14 (5.8%) 8 (10.3%) 29 (15.9%)
Haloperidol*** 108 (50.2%) 45 (57.7%) 58 (34.7%)
Depot 118 (52.9%) 36 (46.2%) 100 (59.9%)
*** p < 0.005
Percentages are the percentage out of each catchment area’s total
number of participants.
Data were missing for 9-17 patients per hospital
ORIGINAL Afr J Psychiatry 2008;11:287-290
AAffrriiccaann JJoouurrnnaall ooff PPssyycchhiiaattrryy • November 2008 228899
lowest haloperidol prescriptions. Differences in depot
antipsychotics use were not significant (p>0.05).
The SANS scores of the three areas were similar, but they
differed significantly in terms of SAPS scores (Table II). Patients at
LGH had the highest SAPS score, which differed significantly from
the scores of VBH patients (post-hoc test: p<0.05). The SAPS
scores from STH patients did not differ significantly from either of
the other two catchment areas.
Discussion
This study found an overall rate of 10% clozapine use across
three Western Cape hospitals, which is lower than the clozapine
rates found in Connecticut, USA – 15%15– and Auckland, New
Zeeland – 26%.16One of the possible reasons for the lower-than-
expected rate of clozapine use may be that clinicians in the APH
hospitals feel that patients are less compliant when it comes to
treatment adherence and regular follow-up. This is an important
variable to consider before commencing treatment, as a special
feature of clozapine is a requirement of regular leukocyte counts
to monitor the risk of agranulocytosis.17 However, there is no
supporting evidence that specifically African patients have
poorer treatment adherence rates than patients of other ethnic
groups and this possibility requires further research. The low
frequency of clozapine use may merely reflect practical
implications such as side-effect profile18, repeated white cell
counts and difficulties related to reintroduction of clozapine after
discontinuation for longer than 48 hours .
We found a rate of antipsychotic polypharmacy of 28.6% ,
which compares poorly to studies in New Zealand16 and the
USA15 that found rates of antipsychotic polypharmacy of 13% and
10%, respectively. Antipsychotic polypharmacy is strongly
discouraged in widely-accepted international guidelines,
including the NICE guidelines.1Polypharmacy may lead to an
increased potential for adverse drug effects, unwanted
pharmacokinetic drug interactions, and an increase in the
cumulative antipsychotic dose increasing the risk of tardive
dyskinesia.2,19
There were significant differences between the three
catchment areas in the use of clozapine and haloperidol. One
possible explanation could be that the patients from each hospital
differed in their clinical presentations. The patient profiles may
differ somewhat between catchment areas, as SAPS scores varied
significantly between sites. Interestingly, the lowest SAPS scores
were found in VBH patients, which were also the patients with the
highest clozapine prescription rates. However, clozapine users
overall had significantly higher SAPS scores than non-clozapine
users. Part of the reason for this discrepancy may be that
clozapine treatment has had an effect in VBH already. These
results should be treated with caution, however, as SANS and
SAPS scores serve only as proxy markers of actual clinical
presentations.
The comparison with international prescription rates, and
significant variation within this population suggest a need for
improved regulation of treatment through standardized
guidelines.
Conclusion
In the interests of mental health care in South Africa, it is
becoming necessary for us to implement practical clinical
guidelines, and make these readily available in the large variety
of settings that characterize this country. An important step is for
specialty societies – in our case, the South African Society of
Psychiatrists (SASOP) – to brand local guidelines, such as those
available at STH, to add the necessary credibility.21Local
guidelines need to take into account appropriate resource
allocation22, ethnic and racial variations in pharmacokinetics23,24,
patients' personal preferences9and the careful monitoring of
adverse drug effects.20 Tools that could enhance the use of these
clinical practice guidelines include the provision of a ‘clinical
practice guidelines summary pocket guide’, and clearly visible ,
‘user-friendly’ hospital performance charts and discharge forms
on which the reasoning behind decisions are noted.25 The
combination of monitoring and implementation of evidence-
based practices is reaching new levels of sophistication, with the
introduction of management computer programmes (e.g.20) that
make it easier to implement guidelines in a structured manner.
However, as it can take many years for guidelines to take effect in
general practice26, the time to start addressing this issue, is now.
References
1. National Institute for Clinical Excellence. Schizophrenia - Full national
clinical guideline on core interventions in primary and secondary care.
ISBN 1-901242-97-8. Trowbridge, Wiltshire, UK: Royal College of
Psychiatrists and the British Psychological Society; 2003|.
2. Miller AL, Hal lCS, Buchanan RW, Buckley PF, Chiles JA, Conley RR, et al.
The Texas Medication Algorithm Project antipsychotic algorithm for
schizophrenia: 2003 update. J Clin Psychiatry. 2004;65:500-8.
3. American Psychiatric Association. American Psychiatric Association
Practice Guidelines. Available from:
http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm.
4. Bauer M. A review of quantitative studies of adherence to mental health
clinical practice guidelines. Har v Rev Psychiatry. 2002;10:138-53.
5. Gilbert DA, Altshuler KZ, Rago WV, Shon SP, Crismon ML, Toprac MG, et
al. Texas Medication Algorithm Project: definitions, rationale, and
methods to develop medication algorithms. J Clin Psychiatry.
1998;59:345-51.
6. Seedat S, Emsley RA, Stein DJ. Land of promise: challenges and
opportunities for research in South Africa. Mol Psychiatry. 2004;9:891-2.
7. Kuno E, Rothbard A. Racial disparities in antipsychotic prescription
patterns for patients with schizophrenia. Am J Psychiatry. 2002;159:567-
72.
8. Herbeck DM, West JC, Ruditis I, Duffy FF, Fitek DJ, Bell CC, et al.
Variations in use of second-generation antipsychotic medication by
race among adult psychiatric patients. Psychiatr Serv. 2004;55:677-84.
9. Segal SP, Bola JR, Watson MA. Race, quality of care, and antipsychotic
prescribing practices in psychiatric emergency services. Psychiatr Serv.
1996;47:282-
Table II. The mean (SD) scores of the Schedule for the
Assessment of Negative Symptoms (SANS) and Schedule for
the Assessment of Positive Symptoms (SAPS) for Xhosa
patients with schizophrenia and schizoaffective disorder, in
the catchment areas of three psychiatric hospitals in the
Western Cape.
Hospital: Lentegeur Stikland Valkenberg
SANS score 9.09 (3.82) 8.18 (4.4) 8.94 (4.17)
SAPS score* 6.85 (4.98) 6.71 (5.06) 5.47 (5.02)
* p < 0.05
ORIGINAL Afr J Psychiatry 2008;11:287-290
AAffrriiccaann JJoouurrnnaall ooff PPssyycchhiiaattrryy • November 2008 229900
10. Niehaus DJ, Koen L, Laurent C, Muller J, Deleuze JF, Mallet J, et al.
Positive and negative symptoms in affected sib pairs with
schizophrenia: implications for genetic studies in an African Xhosa
sample. Schizophr Res. 2005;79:239-49.
11. American Psychiatric Association. Diagnostic and Statistical Manual of
Mental Disorders: DSM-IV. Fourth Edition ed. Washington, DC:
American Psychiatric Association; 2000.
12. Nurnberger JI, Blehar MC, Kaufmann CA, York-Cooler C, Simpson SG,
Harkavy-Friedman J, et al. Diagnostic interview for genetic studies.
Rationale, unique features and training. NIMH Genetics Initiative. Arch
Gen Psychiatry. 1994;51:849-59.
13. Andreasen NC. The scale for the assessment of negative symptoms
(SANS): conceptual and theoretical foundations. Br J Psychiatry.
1989;7:49-58.
14. Andreasen NC, Arndt S, Miller D, Flaum M, Nopoulos P. Correlation
studies of the scale for the assessment of negative symptoms and the
scale for the assessment of positive symptoms: an overview and update.
Psychopathology. 1995;28:7-17.
15. Covell NH, Jackson CT, Evans AC, Essak SM. Antipsychotic prescribing
practices in Connecticut's public mental health system: rates of
changing medications and prescribing styles. Schizophr Bull.
2002;28:17-29.
16. Wheeler A. Atypical antipsychotic use for adult outpatients in New
Zealand's Auckland and Northland regions. N Z Med J. 2006;119:1237.
17. Alvir JMJ, Lieberman JA, Safferman AZ, Schwimmer JL, Schaaf JA.
Clozapine-induced agranulocytosis -- incidence and risk factors in the
United States. N Engl J Med. 1993 July 15, 1993;329(3):162-7.
18. Lieberman JA, Safferman AZ. Clinical profile of clozapine: Adverse
reactions and agranulocytosis. Psychiatr Q. 1992;63(1):51-70.
19. Gaebel W, Weinmann S, Sartorius N, Rutz W, McIntyre JS. Schizophrenia
practice guidelines - international survey and comparison. Br J
Psychiatry. 2005;187:248-55.
20. Joubert AF. Providing quality care to patients with schizophrenia.
Psychiatric Clinics of North America. 2003;26(1):213-30.
21. Leape LL, Weissman JS, Schneider EC, Piana RN, Gatsonis L, Epstein
AM. Adherence to practice guidelines: the role of specialty society
guidelines. Am Heart J. 2003;145:19-26.
22. Rush AJ, Rago VW, Crismon ML, Toprac MG, Shon SP, Suppes T, et al.
Medication treatment for the severely and persistently mentally ill: The
Texas Medication Algorithm Project. J Clin Psychiatry. 1999;60:284-91.
23. Lawson WB. Clinical issues in the pharmacotherapy of African-
Americans. Psychopharmacol Bull. 1996;32:275-81.
24. Lin K, Anderson D, Poland RE. Ethnicity and psychopharmacology:
bridging the gap. Psyciatr Clin North Am. 1995;18:635-47.
25. Brindis R, Sennett C. Physician adherence to clinical practice guidelines:
does it really matter? Am Heart J. 2003;145:13-5.
26. Parks JJ. Implementing practice guidelines: lessons from public mental
health settings. J Clin Psychiatry. 2007;68(suppl 4):45-8.
First Monthly summary of the
Movement for Global
Mental Health
The Movement was launched on October 10th, 2008 and this was announced in an editorial in the
Lancet. You can access this on the website. Since its launch, the Movement has grown impressively.
Until October 30th, these are some key indicators:
293 Institutional Members
31 Institutional Partners
6 Photo Galleries (plus 3 External photo gallery links)
10 Packages of Care
2 Policies
30 Ongoing Research Projects
9 Capacity Building Courses
11 Capacity Building Resources
9 Funders
3 Human Rights Stories
5 Messages of Support
Please keep the momentum going by renewing the message to join through your networks and partners, and getting your own
colleagues and institutions to join up. If we can reach a target of 100 institutions and 1000 individual members by the time of the
summit, we will truly have built up a global coalition for change. Please canvass leaders in your communities to provide 'messages
of support' which can be posted alongside messages from the UN Secretary General, Amartya Sen and other luminaries.
Please also keep on submitting news and events on packages of care, human rights, photo galleries, funders, conferences,
mental health policy documents, research projects and capacity building programs and resources. Oliver Lewis from MDAC has
joined as editor of the human rights pages. If any of you wish to get involved in editing pages, please email the named editors of
those pages (you can find these on the page "About this website" at the bottom of the home page).
Finally, next month we will invite submissions of ideas and suggestions for the program for the Global Mental Health Summit on
September 2nd, 2009 in Athens. The venue has been finalised and the registration fee is 50 euros-book that date now!
(Summary was prepared by Vikram Patel. Suggestions and comments, and volunteers to write these summaries, should be sent to
submissions@globalmentalhealth.org)