Pharmacology & Pharmacy, 2012, 3, 409-416
http://dx.doi.org/10.4236/pp.2012.34055 Published Online October 2012 (http://www.SciRP.org/journal/pp) 1
Antipsychotic and Anticholinergic Drug Prescribing
Pattern in Psychiatry: Extent of Evidence-Based Practice
in Bahrain*
Khalid A. J. Al Khaja1#, Mohammed K. Al-Haddad2, Reginald P. Sequeira1, Adel R. Al-Offi3
1Department of Pharmacology & Therapeutics, Arabian Gulf University, Manama, Bahrain; 2Department of Psychiatry, Arabian Gulf
University, Manama, Bahrain; 3Psychiatric Hospital, Ministry of Health, Manama, Bahrain.
Received May 7th, 2012; revised June 13th, 2012; accepted July 12th, 2012
ABSTRACT
The aim of this study is to determine the antipsychotic prescribing pattern and the prevalence of concurrent anticho-
linergic prescribing in a psychiatric referral hospital. A retrospective audit of prescriptions issued for outpatients was
carried out at the Psychiatric Hospital, the only facility th at provides psychiatric services for bo th inpatients and outpa-
tients in the Kingdom of Bahrain. Antipsychotic monotherapy was prescribed for 89.2% patients, whereas po lytherapy
with two- and thr ee-drugs in 1 0.4% and 0.4%, r espectively. A typical antipsychotics w ere prescribed more of ten (67.7%)
than typical antipsychotics. Risperidone and haloperidol were the most frequently prescribed antipsychotics. Long-act-
ing risperidone injection was the only depot preparation prescribed. The mean antipsychotic dose expressed as chlor-
promazine equivalent (CPZeq; mg/day) was 242 (220 for monotherapy and 414 for polytherapy). The prevalence of
high dose antipsychotic (mean CPZeq > 1000 mg/day) was 1.8%, prescribed at a mean CPZeq dose of 1531 (1925 for
monotherapy and 1137 for polytherapy), mainly attributed to haloperidol. Anticholinergics were co-prescribed for al-
most two third of patients receiving antipsychotics, particularly for those on polytherapy (monotherapy 57.3%; poly-
therapy 87.5 %). Antipsychotic polytherapy, high dose and co-prescription of an oral with a depot antipsycho tic prep ara-
tion were strongly associated with concurrent prescription of anticholinergics. Procyclidine and orphenadrine were the
most often prescribed anticholinergics. In Bahrain, antipsychotic monotherapy is a common practice for outpatients
with psychotic disorders. Some of the antipsychotic polytherapies, dosage strategies, and high prevalence of anticho-
linergic use are therapeutic issues that need to be addressed to foster evidence-based pr e scribing p ra c tice.
Keywords: Anticholinergics; Antipsychotics; Best Evidence; Prescribing; Psychiatry
1. Introduction
Numerous studies have reported that there are wide in-
ter-country [1-4] and intra-country [4-6] variations in
antipsychotic prescribing pattern for patients with psy-
chotic disorders. These variations include the prevalence
of antipsychotic polytherapy compared to monotherapy,
typical versus atypica l antipsychotics, preference for hig h-
dose antipsychotics or depot antip sychotics, and anticho-
linergic co-prescription. Such variations have been at-
tributed to difficulty in adhering to treatment guidelines
and therapeutic alogarithms in clinical practice, differ-
ences in healthcare settings, availability and cost of an-
tipsychotics, introduction of atypical antipsychotics with
improved adverse effects profile and efficacy, and socio-
cultural determinants [3,4,7-9].
Extra-pyramidal symptoms (EPS) such as acute dysto-
nia, akathesia and Parkinsonism are among the most
common adverse effects of antipsychotics. In clinical
practice, anticholinergics are widely used to treat and
prevent antipsychotic—induced EPS. Anticholinergics
should be prudently prescribed because these drugs in
addition to their well-known peripheral side-effects, may
worsen positive symptoms, appear to partially ameliorate
negative symptoms and are associated with impaired
cognitive functio ning of schizo phren ic [10] an d cogn itiv e
impairment in elderly patients [11]. A recent report [12]
has confirmed that there is a wide variation in anticho-
linergic medication prescribing across various countries;
a combination of clinical, social, economic and cultural
factors are the determinants of the use of these drugs
suggesting that there are considerable differences be-
tween treatment guidelines and clinical practice.
*The abstract of this paper was presented at the 19th European Con-
gress of Psychi a try, 12-15 March 2011, Vienna, Aus t ria.
#Corresponding author.

Antipsychotic and Anticholinergic Drug Prescribing Pattern in Psychiatry: Extent of Evidence-Based Practice in Bahrain
410
The initial enthusiasm about the second generation of
atypical antipsychotic drugs has changed into criticism
and debate culminating in the controversial CATIE
(Clinical Antipsychotic Trials of Intervention Effective-
ness), CUtLASS (Cost Utility of the Latest Antipsycho tic
Drugs in Schizophrenia Study) and EUFEST (European
First-Episode Schizophrenia Trial) trials. The debate
seems to be driven more by values than by data; some
place an emphasis on cost, others focus on extra-pyra-
midal side effects, weight gain or efficacy [13,14].
Based on PubMed database searching (up to January
2011) using MeSH terms- antipsychotic/prescribing pat-
tern/Middle East, we were unable to identify any public-
cation in the last 30 years that has explored the antipsy-
chotic prescription p attern in patients with psychotic dis-
orders in Middle Eastern countries. The present study,
therefore, focused on determining the antipsychotic pre-
scribing pattern and the prevalence of concurrent anti-
cholinergic prescribing to outpatients in a psychiatric
referral hospital .
2. Material and Methods
2.1. Setting
The Kingdom of Bahrain, with a population of 1.1 mil-
lion is a group of small islands located in the Arabian
Gulf. A Directorate of Health Centres, has a network of
21 primary-care health centres spread across the islands
and provides free health care services to both citizens and
expatriates, including dispensing of essential drugs. Pa-
tients requiring psychiatric consultation are referred to
the Psychiatric Hospital under the Ministry of Health.
There are several well-established private hospitals.
This prescription-based study was carried out at the
Psychiatric Hospital, the only public hospital for psychi-
atric services in Bahrain. This hospital with 201 beds
provides both inpa tient and outpatient services, and is the
only facility for substance abuse rehabilitation in the
country.
Data source and collection: All p r escriptions d ispen sed
gratis at Psychiatric Hospital pharmacy for outpatients
during September 2007 were collected. Prescriptions were
initially screened and those with antipsychotics were
analyzed. The following inclusion criteria were used: 1)
prescriptions comprising one or more antipsychotic(s)
alone or with an anticholinergic agent; 2) prescriptions
with a refill period of minimum six weeks (in order to
ensure that dose-titration has been achieved and to avoid
prescription duplication). Prescriptions wherein antipsy-
chotics were co-prescribed with antidepressant(s) were
excluded to avoid the potential influence of intrinsic an-
ticholinergic activity due to antidepressant(s) on pre-
scribing rate of anticholinergic medications. The fol-
lowing data were collected: age and gender for each pa-
tient; type, route of administration and dose of antipsy-
chotics; dose and type of co-prescribed anticholinergics.
2.2. Drugs
Antipsychotics included on the psychiatric hospital es-
sential drug list at the time of data collection were typical
antipsychotics with high potency (haloperidol, trifluop-
erazine), moderate potency (zuclopenthixol), and low
potency (chlorpromazine and thioridazine). Atypical an-
tipsychotics included clozapine, olanzapine, risperidone
and sulpiride. Parenteral preparations included decanoate
formulations of haloperidol, flupenthixol, fluphenazine
and zuclopenthixol, and risperidone long-acting injection
(LAI).
2.3. Operational Definitions
According to evidence-based criteria [15] antipsychotic-
induced EPS were categorized as follows: absent or neg-
ligible (0) for clozapin e; low (1+) for olanzapin e, sulpirid e
and thioridazine; moderate (2+) for chlorpromazine and
risperidone; moderately severe (3+) for trifluoperazine
and zuclopenthixol; and severe (4+) for haloperidol. Con-
version of oral antipsychotic dose to chlorpromazine
equivalent (CPZeq) dose was derived from evidence-
based published data [1,15-17]. Antipsychotic polyther-
apy (combination antipsychotic therapy) is defined as
concomitant use of >2 antipsychotics (either typical/
atypical/combination of both). High-dose antipsychotics
are defined as mean CPZeq doses > 1000 mg/day [18].
As per Diagnostic and Statistical Manual (DSM)-IV cri-
teria, psychotic disorders include schizophrenias, schizo-
affective and schizoform disorders. In this report, antip-
sychotics, particularly atypical, may also be used as off-
label medications for dementia, major depression disor-
ders, autism spectrum disorders, obsessive compulsive
disorders, combat-related post traumatic stress disorders
and generalized anxiety disorders.
2.4. Statistical Analysis
Data were analyzed using Statistical Package for the So-
cial Sciences (SPSS/PC+, version 15). Chi-square (x2)
and Fisher’s exact tests, as appropriate, were used to test
differences between proportions, and two-tailed t-test
was used for continuous variables. A p-value of <0.05
was considered statistically significant.
3. Results
Out of 1591 prescription s, 454 (2 8.5%) met th e inclus ion
criteria. However, 1137 outpatient prescriptions (71.4%)
were excluded because: 912 (57.3%) were on antide-
pressant(s) and 225 (14.1%) were on antipsychotic
co-prescribed with antidepressant(s). The mean age (±SD)

Antipsychotic and Anticholinergic Drug Prescribing Pattern in Psychiatry: Extent of Evidence-Based Practice in Bahrain
411
of patients who were on antipsychotic monotherapy was
38.4 ± 15.1 (median = 39; range 5 - 80 years), whereas
38.7 ± 11.7 (median = 41; range 17 - 63 years) was for
patients who were on antipsychotic polytherapy. No sig-
nificant differences with respect to mean age of patients
prescribed antipsychotic monotherapy and polytherapy
was evident. The proportion of male patients was 59.8
and 55.1 for mono and polytherapy, respectively (p =
0.541). Antipsychotic and anticholinergic medication
characteristics are shown (Table 1). Overall 61% of pa-
tients (57.3% in monotherapy; and 87.5% polytherapy)
on antipsychotic therapy were prescribed a single anti-
cholinergic drug: procyclidine (41%, n = 186/454), or-
phenadrine (10.8%, n = 49/454), benzatropine (7.9%, n =
36/454), and trihexyphenidyl (0.9%, n = 4/454).
3.1. Antipsychotic Monotherapy
Prescribing patterns of antipsychotic monotherapy are
shown (Table 2). A total of 89.2% (n = 405/454) outpa-
Table 1. Medication characteristics.
Antipsychotic monotherapy Antipsychotic polytherapy p-value
Rate of antipsychotic therapy n (%) 405 (89.2) 49a (10.8)
Mean CPZeq dose (mg/day) 220 ± 251 414 ± 278 <0.0001
Median (mg) 150 350
Range (mg) 12.5 - 3000 25 - 1250
Dose > 1000 mg CPZeq n (%) 4 (1) 4 (8.2) 0.0006
Mean CPZeq doses of antipsychoticsb (median) 1925 ± 788 (1750) 1137 ± 75 (1100)
Depot antipsychotic, n (%) 19 (4.7) 9c (18.4) 0.001
Prescription rate of anticholinergic, n (%) 232 (57.3) 43 (87.5) <0.000
Anticholinergics mean dose ± SD (n)
Procyclidine 8.5 ± 4.2 (156) 11.2 ± 4.1 (30) 0.004
Orphenadrine 81.8 ± 37.5 (43) 116.7 ± 40.8 (6) 0.039
Benzatropine 3.8 ± 1.4 (30) 3.3 ± 1 (6) 0.525
Trihexyphenidyl 4.0 ± 1.7 (3) 10 ± 0 (1) -
CPZeq = chlorpromazine equivalents; aonly 2 patients (0.4%) were on three-antipsychotic combination; bmean CPZeq doses of antipsychotics > 1000 mg; c2
out of 9 patients who received risperidone long-acting injection were on antipsychotic three-drug combination.
Table 2. Prescribing patterns of antipsychotic monotherapy in psychiatric hospital outpatients.
Antipsychotics Number of
patients (%) Anticholinergic prescribed concurrently (%) Anticholinergic co-prescribing rate per antipsychotic Antipsychotic mean ± SD doses (median) CPZeq mean ±SD doses (median)
Typical:
Chlorpromazine (2+) 29 (7.2) 16 (4) 55.5 153 ± 96 (100) 153 ± 96 (1 00)
Haloperidol (4+) 42 (10.4) 30 (7.4) 71.2 10.8 ± 11.1 (10) 540 ± 556 (500)
Thioridazine (1+) 1 (0.2) - - 50 ± 0 (50) 50 ± 0
Trifluoperazine (3+) 33 (8.1) 20 (4.9) 60. 5 9.0 ± 8 .9 (5) 191 ± 181 (100)
Zuclopenthixol (3+ ) 17 (4.2) 15 (3.7) 88.1 23.5 ± 10.6 (20) 94 ± 42 (80)
Subtotal 122 (30.1) 81 (20) 66.4 288 ± 388 (155)
Atypical:
Clozapine (0) 14 (3.5) 5 (1.2) 34.3 278 ± 137 (278) 557 ± 275 (575)
Olanzapine (1+) 38 (9.4) 14 (3.5) 37.2 9.2 ± 5.6 (7.5) 184 ± 112 (150)
Risperidone (2+) 194 (47.9) 125 (30.9) 64.5 3.5 ± 2 (3) 174 ± 97 (150)
Risperidone LAI (2+) 14 (3.5) 2 (0.5) 5.7 31.3a ± 8.8 (31) **
Risperidone oral + LAI (2+) 5 (1.20) 4 (1) 83.3 ** **
Sulpirideb (1+) 18 (4.4) 1 (0.2) 4.5 169 ± 75 (200) 85 ± 37 (100)
Subtotal 283 (69.9) 151 (37.3) 53.3 193 ± 146 (150)
Total 405 (100) 232 (57.3) 220 ± 251 (150)
(0), (1+), (2+), (3+) and (4+) represent antipsychotics with negligible, low, moderate, moderately severe, and severe extrapyramidal symptoms, respectively;
CPZeq = chlorpromazine equivalents; LAI = long-acting injection; amean dose of intramuscular LAI risperidone mg/fortnight; ban atypical antipsychotic struc-
turally similar to amisulpride; **mean & median dose not calculated.

Antipsychotic and Anticholinergic Drug Prescribing Pattern in Psychiatry: Extent of Evidence-Based Practice in Bahrain
412
tients were prescribed antipsychotic monotherapy; of
these, 69.9% (n = 283/405) were on atypical antipsy-
chotics such as oral risperidone (47.9%, n = 194), olan-
zapine (9.4%, n = 38), sulpiride (4.4%, n = 18), clozapine
(3.5%, n = 14), risp eridone long-acting injection (3.5 %, n =
14) and oral plus LAI risperidone (1.2%, n = 5). Risper-
idone, both oral and LAI, was the most frequently pre-
scribed antipsychotics, accounted for 75.3% (n = 213/283)
of all atypical antipsychotic monotherapies. Nevertheless,
30.1% (n = 122/405) of patients received monotherapy
with typical antipsychotics: haloperidol (10.4%, n = 42),
trifluoperazine (8.1%, n = 33), chlorpromazine (7.2%, n
= 29), zuclopenthixol (4.2%, n = 17) and thioridazine
(0.2%, n = 1). Haloperidol accounted for 34.4% (n =
42/122) of all typical antipsychotic monotherapies. The
three antipsychotics most frequently prescribed as mono-
therapy were risperidone (52.6%), followed by haloperi-
dol (10.4%) a n d ol anzapine (9.4%) .
Anticholinergics were prescribed for 57 .3% of patien ts
on antipsychotic monotherapy. The rate of individual
antipsychotics along with anticholinergics co-prescribed
were: zuclopenthixol (88.1%), risperidone oral + LAI
(83.3%), haloperidol (71.2%), oral risperidone (64.5%),
trifluoperazine (60.5%), chlorpromazine (55.5%), olan-
zapine (37.2%), clozapine (34.3%), risperidone LAI
(5.7%), and sulpiride (4.5%).
3.2. Antipsychotic Polytherapy
The prescribing pattern s of antipsycho tic polytherapy are
shown (Table 3). Antipsychotic polytherapy was used
Table 3. Prescribing patterns of antipsychotic polytherapy in psychiatric hospital outpatients.
Antipsychotics Number of
patients (%) Anticholinergic prescribed concurrently (%)
Anticholinergic
co-prescribing rate per
antipsychotic
Antipsychotic mean
± SD doses (median) CPZeq mean ± SD doses (median)
Typical + typical:
Chlorpromazine (2+) plus
Haloperidol (4+) 2 (4.3) 2 (4.3) 100 12.5 ± 10.6 (12.5) 700 ± 565 (700)
Zuclopenthixol (3+) 1 (2.1) 1 (2.1) 100 60 ± 0 (60) 290 ± 0 (290)
Subtotal 3 (6.4) 3 (6.4) 100 563 ± 464 (300)
Atypical + atypical:
Risperidone (2+) plus
Olanzapine (1+) 4 (8.5)a 3 (6.4) 75.3 7.5 ± 3.5 (7.5) 275 ± 125 (300)
Sulpiride (1+) 4 (8.5)b 3 (6.4) 75.3 117 ± 76 (100) 225 ± 90 (250)
Subtotal 8 (17) 6 (12.8) 75.3 275 ± 100 (300)
Atypical + typical:
Clozapine (0) plus
Zuclopenthixol (3+) 1 (2.1) 1 (2.1) 100 10 ± 0 (10) 540 ± 0 (540)
Olanzapine (1+) plus
Haloperidol (4+) 2 (4.3) 2 (4.3) 100 7.5 ± 3.5 (7.5) 575 ± 176 (575)
Trifluoperazine (3+) 2 (4.3) 2 (4.3) 100 7.5 ± 3.5 (7.5) 220 ± 113 (220)
Zuclopenthixol (3+ ) 2 (4.3) 2 (4.3) 100 30 ± 28.3 (30) 270 ± 183 (270)
Risperidone (2+) plus
Chlorproma zi ne (2+) 7 (14.9) 6 (12.8) 85.9 93 ± 53 (10 0) 293 ± 93 (300)
Haloperidol (4+) 7 (14.9)c 6 (12.8) 85.9 13.3 ± 7.5 (15) 791 ± 406 (850)
Trifluoperazine (3+) 8 (17)d 7 (14.9) 87.6 7.4 ± 5.1 (5) 408 ± 198 (400)
Zuclopenthixol (3+) 6 (12.8) 6 (12.8) 100 23.3 ± 15 (20) 308 ± 110 (310)
Sulpiride (1+) plus
Trifluoperazi ne (3+) 1 (2.1) - - 5 ± 0 (5) 125 ± 0 (125)
Subtotal 36 (76.7) 32 (68.3) 89 444 ± 285 (400)
Total 47 (100) 41 (87.5) 414 ± 278 (350)
(0), (1+), (2+), (3+) and (4+) represent antipsychotics with negligible, low, moderate, moderately severe, and severe extrapyramidal symptoms, respectively;
CPZeq = chlorpromazine equivalents; a2 out of 4 p atients r eceived r isper idone l ong-acti ng inj ection ( LAI); b1 ou t of 4 p atient s received risp erdone LAI ; c1 out
of 7 patients received risperidone LAI; d3 out of 8 patients received risperidone LAI.

Antipsychotic and Anticholinergic Drug Prescribing Pattern in Psychiatry: Extent of Evidence-Based Practice in Bahrain 413
for 10.8% (n = 49/454) outpatients; of these 10.4% (n =
47/454) were on two antipsychotics, whereas 0.4% (n =
2/454) were on three antipsychotics. Pattern of antipsy-
chotic two-drug therapy in descending order was as fol-
lows: an atypical with a typ ical antip sycho tic (76.6 %, n =
36/47), two atypical antipsychotics (17%, n = 8/47), and
two typical antipsychotics (6 .4 %, n = 3/47 ; Table 3). The
antipsychotic two-drug combinations prescribed most
often were risperidone/trifluoperazine (17%), followed by
risperidone with either chlorpromazine (14.9%) or halop-
eridol (14.9%) or zuclopenthixol (12.8%). The three an-
tipsychotics most commonly prescribed as polytherapy
were risperidone (73.5%), followed by haloperidol (22.4 % )
and trifluoperazine (22.4%).
Anticholinergics were prescribed for 87 .5% of patien ts
on antipsychotic polytherapy (two antipsychotic combi-
nation); a typical antipsychotic co-prescribed with an-
other typical or with an atypical antipsychotic had a
greater likelihood of being prescribed with anticholiner-
gic medications (Table 3).
Antipsychotic three-drug combination comprising chlor-
promazine plus zuclopenthixol plus risperidone LAI was
prescribed for 0.4% (n = 2/454) outpatients (Data not
shown).
4. Discussion
Antipsychotics: This study provides insights, based on
audit of prescriptions, into the prescribing patterns of
antipsychotic and anticholinergic medications for outpa-
tients with psychotic disorders receiving treatment at a
public referral hospital in Bahrain. The data suggest that
atypical antipsychotic monotherapy is the most preferred
treatment. Antipsychotic monotherapy was prescribed for
most of the patients (89.2%), a rate which is comparable
to 86.5% reported in New Zealand [5], 87% in Australia
[19], 87% - 91% in USA [20,21] and 82.6% in UK [22],
consistent with clinical guidelines [8,16]. With the ex-
ception of haloperidol and clozapine (Table 2), the indi-
vidual antipsychotic daily dose for other monotherapies
was generally lower than the recommended therapeutic
range [8,18], deemed to be inadequate for many with
psychosi s [ 8,18,23].
Despite the superior clinical effectiveness, EPS safety
profile [24], and as being the preferred drug for patients
with schizophrenia who are unresponsive to adequate
multiple antipsychotic monotherapy trials [8,18], clozap-
ine is significantly under-prescribed and accounted for
only 3.3% of overall antipsychotics (Tables 2 and 3). In
contrast, other studies reported clozapine to be the most
commonly prescribed antipsychotic medication in up to
25% - 60% of schizophrenic inpatients in China [25] and
in 34.5% of outpatients in New Zealand [2 6]. In general,
limited clinical utility of clozapine appears to be due to
propensity to cause agranulocytosis and the need for
mandatory hematological monitoring of patients [27].
Psychiatrists, therefore, may find it appealing to pre-
scribe antipsychotic polytherapy rather than to prescribe
clozapine [21]. Moreover, clozapine was included in the
drug list only few months prior to data collection and
prescribing was restricted to consultants in psychiatric
hospital in Bahrain at that time.
The combination antipsychotic therapy in our study
was rarely used (10.8%), and conforms with expert guid e-
lines [8]. A low trend towards polytherapy may be re-
lated to the nature of study population in our study, i.e.,
outpatients. Of note, symptoms of psychotic disorders in
outpatients perhaps are less severe and persistent than
those of inpatients. Thus outpatients may less often be
prescribed with antipsychotic polytherapy than inpatients
[21]. In our study, concomitant antipsychotic therapy (a
typical with an atypical) comprised 76.6% of overall an-
tipsychotic polytherapy (Table 3) which is in line with
rates reported elsewhere [5,21]. Moreover, polytherapy
in our survey may have resulted from adding a typical to
an atypical (top up strategy) to improve persistent posi-
tive symptoms [21,28], or adding an atypical to a typical
to switch to the atypical regimen [21] or cross-tapering
designed to chan ge antipsychotic regimen (cross-titration
trap) [2,21,28]. A prospective study combining quantita-
tive and qualitative approaches can address the primary
reason for the use of anti psychotic po lytherapy.
The overall prevalence of high-dose antipsychotics
was 1.8%, prescribed at a mean daily CPZeq dose of
1531 ± 668 mg (median = 1225, data not shown). High-
dose antipsychotic practice was found to be more likely
related to antipsychotic polytherapy (8.2% [polytherapy]
vs. 1% [monotherapy]; p = 0.0006, Table 1); it is mainly
attributed to the high dose of haloperidol prescribed as
both monotherap y an d co mbinatio n an tip sycho tic th erap y.
The rate of high-dose antipsychotic was equivalent to
that reported recently for psychiatric outpatients in Hong
Kong (1.8%) [29]. Moreover, we found that the rate of
high-dose antipsychotic monotherapy (1%) was less than
the 2.5% reported for outpatients in USA [22].
Anticholinergics: Notwithstanding considerable dif-
ferences between anticholinergics, these medications are
the mainstay for treatment of EPS-induced by antipsy-
chotics. EPS occur mostly with typical antipsychotics,
particularly those with high potency, and occasionally
with atypical antipsychotics. We found that anticholiner-
gic drugs were co-prescribed extensively along with both
typical and atypical antipsychotics. The prevalence of
anticholinergic use was 57.3% and 87.5% for outpatients
on antipsychotic monotherapy and polytherapy, respec-
tively. These rates were significantly greater than those
reported for outpatients elsewhere [2,5,9,30] (regardless
of type and therapy of antipsychotics studied) which
suggests the possibility that cultural and institutiona l pra-

Antipsychotic and Anticholinergic Drug Prescribing Pattern in Psychiatry: Extent of Evidence-Based Practice in Bahrain
414
ctices would have contributed to these findings. In our
study anticholinergics may have been routinely pre-
scribed even in the absence of EPS, although exp erts dis-
agree about the prophylactic use of these agents [16,18].
This therapeutic dilemma ha s been addressed by Gjerden
et al. [31] who viewed that anticholinergic use appears to
be superfluous for at least one-third of patients, and their
use exceeded the incidence of EPS [32].
Our study has identified that antipsychotic polyth erapy
is a key predictor for the use of anticholinergics since
both proportion and mean dose of co-prescribed anticho-
linergic (specifically for most often prescribed procycli-
dine and orphenadrine) increase proportionally with the
increase in number of prescribed antipsychotic medica-
tions (Table 1). Anticholinergics should be prudently
prescribed because these drugs, in addition to their pe-
ripheral side effects, can impair cognition, especially in
the elderly patients [11]. Anticholinergics may worsen
positive symptoms, appear to partially ameliorate nega-
tive symptoms, and are associated with impaired cogni-
tive functioning of schizophrenic patients [10]. Prescrib-
ers should be aware of the potential anticholinergic—re-
lated peripheral side effects, particularly, when anti-cho-
linergic medications are prescribed with antipsychotics
that have greater intrinsic anticholinergic activity, such as
the phenothiazines.
We also found that high anticholinergic drug preva-
lence is less likely to b e associated with the mean CPZeq
doses, particularly atypical antipsychotics (Table 2).
These findings suggest that overt anticholinergic prescrib-
ing may arguably be superfluous for several reasons. Fir s t,
clozapine and olanzapine have significant intrinsic anti-
cholinergic activity, which may be partly responsible for
fewer EPS and obviates the need for an anticholinergic
agents [33]. Approximately 35% of patients who received
these medications were prescribed anticholinergic medi-
cations (Table 2), perhaps to mitigate clozapine-induced
hypersalivation [34]. Second, dose-dependent EPS have
been reported to appear in 60% to 70% of patients taking
risperidone at dosages of >6 mg/day (i.e., >300 mg/day
CPZeq) [35-37]. Nonetheless, approximately 65% of
patients on risperidone monotherapy (who received a
mean dose of 3.5 mg/day, i.e., 175 mg/day CPZeq) were
prescribed anticholinergic drugs (Table 2). Third, most
guidelines converge on a recommendation that doses of
antipsychotics should range between 300 and 1000 mg
CPZeq in order to achieve effective control of positive
symptoms [8,18] while avoiding EPS and the use of an-
ticholinergic drugs [38]. In contrast to this, the mean
CPZeq doses especially as monotherapy (Table 2), the
most sought practice in our cohort, was significantly be-
low this range [8,18,23]. Fourth, atypical antipsychotics
as a class, generally produce fewer or no EPS relative to
typical antipsychotics, which can produce clinically sig-
nificant EPS in 60% of patients [33]. Moreover, risper-
idone is considered the most likely atypical antipsychotic
agent to produce EPS [15]. It is, therefore, the high pre-
valence of anticho lin ergic co-p rescrip tion in patien ts who
received atypical antipsychotic monotherapy (53.3%; Ta-
ble 2) can be attributed, in addition to the suggested su-
perfluous prescribing trend, to the frequent use of this
agent in this group.
Sulpiride was rarely prescribed with anticholinergic
medications (4.5%, Table 2). This may be attributed to: 1)
its classification as an atypical benzamide antipsychotic
associated with low incidence of EPS; and 2) its pre-
scription in low dose (85 mg CPZeq), a dose which is
significantly lower than the recommended antipsychotic
therapeutic range (400 - 1200 mg) required for control-
ling both negative and positive symptoms of schizophre-
nia [16].
In our study, different aspects related to prescription
patterns of antipsychotics and the concurrent prescript-
tions of anticholin ergics app ear either to be at variance or
in agreement with a large body of literature worldwide.
These inter-country variations may be due to several de-
terminants such as healthcare setting, availability and
cost of antipsychotics, population sample (outpatients
versus inpatients), treatment settings (psychiatric ho spital
versus psychiatric unit in a general hospital or emergency
setting versus nonemergency setting), standard treatment
guidelines, psychiatrists’ training background and socio-
cultural context of clinical presentations [1,39]. We sug-
gest that the cultural or institutionally biased approach
may play a determinant role in prescribing patterns of
these drugs. Moreover, inter-racial differences in effect-
tive therapeutic dosage of antipsychotics in treating psy-
chotic symptoms and variations in psychotic symptoms
response to antipsychotic therapy should also be consid-
ered [39,40].
4.1. Limitations of the Study
Several limitations need to be considered while inter-
preting the findings of this study. Since the diagnosis of
psychotic disorder is not stated in prescriptions, the
therapeutic rationale for antipsychotics prescribed is un-
certain. Moreover, factors that would influence the an-
tipsychotic selection such as history of previous treat-
ment response, drug safety in overdose, overall adverse
effect profile, comorbid condition, non-psychotic medi-
cations used, and patient preference, if any, are uncertain.
Therefore the observations of this study need to be inter-
preted with caution.
4.2. Conclusion
In Bahrain, antipsychotic monotherapy is the common
practice for outpatients with psychotic disorders. Some

Antipsychotic and Anticholinergic Drug Prescribing Pattern in Psychiatry: Extent of Evidence-Based Practice in Bahrain 415
of the antipsychotic polytherapies, dosing strategies and
high prevalence of anticholinergic use are therapeutic
issues that need to be addressed to foster evidence-based
prescribing practice.
5. Acknowledgements
We acknowledge the help and assistance given to us by
Mrs. Radha Raghavan in preparing and typing of this
manuscript.
6. Conflict of Interest
There is no conflict of interest to declare. This work is
not supported or funded by any drug co mpany.
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