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East Asian Arch Psychiatry 2014;24:68-74

Original Article

Medication Adherence in Schizophrenia: A


Comparison between Outpatients and Relapse
Cases

SM Razali, MZAM Yusoff

Abstract
Objective: Adherence to medication is essential for maximising the outcomes of patients with
schizophrenia as the consequences of poor adherence are devastating. The study aimed to compare
medication adherence between patients with relapse schizophrenia and those attending psychiatric
follow-up clinics, and to determine the factors affecting adherence.
Methods: This was a cross-sectional study involving 70 patients with schizophrenia who were divided
equally into 2 groups. Medication adherence was assessed with the Medication Adherence Rating Scale.
Appropriate instruments were used to measure insight, social support, and psychopathology. Various
socio-demographic and clinical variables were explored to find associations with medication adherence.
Results: Medication adherence among patients with schizophrenia was poor; 51% of the patients did
not adhere to a medication regimen. Adherence was better in outpatients with schizophrenia (61%) than
in relapse cases (39%), although the difference was not statistically significant (t = 1.70; p = 0.09).
Besides, relapse patients had significant higher number of admission (X2 = 22.95; p < 0.05) and severe
psychopathology (t = 29.96; p < 0.05), while perceived social support was significantly better in
outpatients with schizophrenia (t = 2.90; p < 0.05). Frequency of admission (adjusted b = 0.55; 95%
confidence interval [CI], -0.99 to -0.10; p < 0.05) and psychopathology (adjusted b = 0.12; 95% CI,
-0.24 to -0.01; p < 0.05) were also significantly associated with medication adherence.
Conclusion: Medication adherence among both groups of patients with schizophrenia was poor. If
adherence is addressed appropriately, the number of admissions and severity of psychopathology could
be improved.
Key words: Patient compliance; Psychopathology; Schizophrenia; Social support

70

51%

61% 39%

t =1.70 p=0.09
X2=22.95p<0.05
t =29.96p<0.05

t =2.90p<0.05b=0.5595%=
0.99
0.10p < 0.05b=0.1295%=0.24
0.01
p<0.05

Medication Adherence in Schizophrenia

68

2014 Hong Kong College of Psychiatrists

East Asian Arch Psychiatry 2014;24:68-74

Dr Salleh Mohd Razali, MD, MPM, FAMM, Discipline of Psychological and


Behavioural Medicine, Faculty of Medicine, Universiti Teknologi Mara,
Sungai Buloh Campus, 47000 Sungai Buloh, Selangor, Malaysia.
Dr Muhammad Zul Azri Mohammad Yusoff, MD, MMed (Psychiatry),
Department of Psychiatry General Hospital Kota Bharu, 15200 Kota Bharu,
Kelantan, Malaysia.

Original Article

relapse

Address for correspondence: Dr Salleh Mohd Razali, Discipline of


Psychological and Behavioural Medicine, Faculty of Medicine, Universiti
Teknologi Mara, Sungai Buloh Campus, 47000 Sungai Buloh, Selangor,
Malaysia.
Tel: (60-3) 6126 7333; Fax: (60-3) 6126
5224; Email: razali6403@salam.uitm.edu.my
Submitted: 9 October 2013; Accepted: 18 November 2013

Introduction
Medication adherence or compliance is defined as the
extent to which a persons behaviour coincides with the
prescribed medical advice.1 Adherence is best viewed as
continuously
disturbed
rather
than
naturally
dichotomous; total adherence or non-adherence is rare.2
Rates of medication non- adherence among patients with
schizophrenia vary widely; a figure of up to 90% has been
reported, depending on the setting, patient population, and
adherence measures.3,4 The majority of experts believe that
patients with schizophrenia or bipolar disorder on average
takes only 51% to 70% of the prescribed medications.5
Adherence to treatment has a significant impact on the
prognosis of schizophrenia. Good medication adherence
generally contributes to an improvement in clinical
outcome, which leads to a reduced rate of rehospitalisation,
higher rates of employment, and improved quality of life
and functioning.6
The reasons for poor treatment adherence are
complex and heterogeneous.7,8 From patient perspective,
these include forgetting to take the medication, losing or
running out of medication, thinking that it is not needed,
not wanting to take the drug, and fear of side-effects.9
This study aimed to determine the socio-demographic and
clinical factors associated with medication adherence in
patients with schizophrenia, and compare the difference in
medication adherence between currently admitted (relapse
schizophrenia) and those attending psychiatric followup clinics (outpatients with schizophrenia). Comparison
between both groups of patients shall give us an insight
into whether medication adherence is the ultimate factor in
relapse of the illness.

Methods
Study Subjects and Design
This was a cross-sectional study which used universal
sampling to recruit the study sample. Patients with
schizophrenia attending psychiatric follow-up clinics and
those currently admitted to the psychiatric ward (for
East Asian Arch Psychiatry 2014, Vol 24, No.2

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69

Medication Adherence in Schizophrenia

of the illness) of Hospital Universiti Sains Malaysia (USM)


during the study period were screened for the study. The
inclusion criteria were patients meeting the DSM-IV 10
diagnostic criteria of schizophrenia and aged between 18
and 65 years. Outpatients with schizophrenia were
included provided they had not been admitted in the past 2
years. Patients with co-morbid substance dependence
(DSM-IV)10 or mental retardation or who refused to give
written informed consent were excluded. Written informed
consent was obtained from all patients. The study protocol
was approved by the Human Research Ethical Committee
of USM. After obtaining socio-demographic and clinical
profiles, the selected patients were assessed with the
appropriate tools. Outpatients with schizophrenia were
assessed at the clinic, while patients with relapse
schizophrenia were assessed in the ward as soon as they
were stable. Although the same scale was used to assess
the medication adherence in both groups, adherences in
the relapse cases were referred to the medication
adherence behaviour before the present admission, not
during the ward stay. This was clarified to the patients in
the assessment form. All assessments were performed by
the second author (attending psychiatrist).

Rating Instruments
Medication Adherence Rating Scale
Patients medication adherence was assessed using a
modified Malay version of Medication Adherence Rating
Scale (MARS).2 The original MARS is a 10-item selfrating scale with yes / no response. After consulting the
original author, only 4 items pertaining to medication
adherence behaviour were utilised. They included: (1) Do
you forget to take your medication? (2) Are you careless
at times about taking your medication? (3) When you
feel better, do you sometimes stop taking your
medication? and (4) Sometimes, if you feel worse when
you take the medicine, do you stop taking it?. The other
items which are not directly related to medication
adherence were not utilised: items 5 to 8 measured the
attitudes towards taking medication, and items 9 and 10
assessed negative side-effects and attitude towards
psychotropic medications. Total score of MARS ranged
from 0 (low likelihood of medication adherence) to 10
(high likelihood).11 For the 4-item scale, a score of
3 indicated adherence. In the validation study conducted
earlier, we found that MARS had acceptable validation
indexes. The internal consistency coefficient (Cronbachs
alpha) was 0.75, which was comparable with that of the
previous study.2
Insight
and
Treatment
Attitude
Questionnaire
The Insight and Treatment Attitude Questionnaire (ITAQ)
is an 11-item rating scale to evaluate patient recognition
of psychiatric illness and need for treatment, particularly
schizophrenia.12 Each question is scored between 0 and
2 with a maximum possible score of 22. Poor insight is
associated with a score from 0 to 7, fair insight 8 to 14, and
good insight 15 to 22.
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East Asian Arch Psychiatry 2014, Vol 24, No.2

SM Razali, MZAM Yusoff

Multidimensional Scale of Perceived Social Support


The Multidimensional Scale of Perceived Social Support
(MSPSS) is a 12-item instrument designed to assess
perceptions about support from family, friends, and
significant others.13 The items are divided into factor
groups relating to the source of support, with scores
ranging from 1 to 7. High scores indicate high levels of
perceived support. In this study, we used a validated
Malay version of MSPSS.14 The instrument displayed good
internal consistency (Cronbachs alpha = 0.89) and high
test-retest reliability (Spearmans rho = 0.77; p < 0.001).

of the participants in both groups were male. There were


no statistical differences between the 2 groups in terms of
age, gender, education level, marital status, occupation,
and personal income. In terms of clinical characteristics,
relapse cases had a significantly higher admission rate
than outpatients with schizophrenia (X2 = 22.95; p < 0.05;
Table 1). However, no significant difference was found in
the duration of illness and type of prescribed antipsychotics
between the 2 groups.

Brief Psychiatric Rating Scale


The Brief Psychiatric Rating Scale (BPRS) is an 18-item
scale which is divided into psychotic and depressive
subscales.15 Each item is scored on a 4-point scale (ranging
in severity). There are 6 items in the depressive subscale
and another 12 items in the psychotic subscale. The BPRS
is widely used to assess the psychopathology of
schizophrenia and related psychosis.

Non-adherence was found in about half of the patients


(51%). Specifically, non-adherence in outpatients with
schizophrenia was lower (39%) than in relapse cases
(61%). However, the difference in medication adherence
between the 2 groups did not reach statistical significance
(t = 1.70, p = 0.09). In terms of perceived social support,
outpatients with schizophrenia had a significantly higher
MSPSS score (62.7) than the relapse cases (53.0; t = 2.90,
p < 0.05).
Outpatients with schizophrenia had better mean
ITAQ scores compared with the relapse cases. In general,
the outpatients had fair insight while patients with relapse
schizophrenia had poor insight. Although the severity of
the psychotic symptoms as measured by the BPRS was
relatively low in both groups, the BPRS total score and
BPRS psychotic subscore were both significantly higher in
patients with relapse schizophrenia than the outpatient
group (t = 29.96, p < 0.05; t = 31.66; p < 0.05
respectively). Thus, relapse cases had significantly more
severe symptoms than outpatients with schizophrenia
(Table 2).

Sample Size and Statistical Analysis


The calculated sample size was 30 in each group. All data
entries and analyses were processed using the Statistical
Package for the Social Sciences (SPSS) Windows version
20. The associations between the demographic data and
clinical status of inpatient and outpatient groups were
analysed using Pearsons Chi-square test and independent
t test. Association between medication adherence,
psychopathology, insight, and perceived social support
of inpatient and outpatient groups were analysed using
independent t test. Regression analysis was performed to
examine the association between insight, perceived social
support, and psychopathology with medication adherence.

Results
Socio-demographic and Clinical Characteristics
A total of 70 patients participated in this study, with equal
number in each group. The mean ( standard deviation)
age of the patients was 33 8 years. Most of the patients
were Malays (97%), more than half were male (57%), and
the majority was single (63%). Although more than 90% of
the patients had either completed secondary school or
tertiary education, the majority of them (59%) was
unemployed. Therefore, more than half of them (54%) had
a monthly income of < 100 Malaysia Ringgit (about 31
USD). Nearly half of the patients (44%) had schizophrenia
of >10 years. About half of the patients (53%) had a history
of admission of 1 to 5 times. All patients were prescribed
antipsychotic medication and about two-thirds (64%) were
on atypical antipsychotic drugs.

Group Comparison of Socio-demographic and


Clinical Characteristics
The mean age of inpatients and outpatients was 33 10
years and 33 8 years, respectively, and more than half

Group Comparison of Medication Adherence,


Psychopathology, Insight, and Social Support

Relationship with Medication Adherence


Regression analysis was used to explore the relationship
between socio-demographic factors and medication
adherence. The relationship was first examined using
simple linear regression (SLR). The analysis then
proceeded to multiple linear regression (MLR). All the
variables that met the initial screening criteria (p < 0.25)
were entered into MLR. After controlling for age, gender,
and duration of illness, the MLR analysis showed a
significant negative linear relationship between the number
of admissions and total MARS score. Any admission to a
psychiatric ward would reduce the total MARS score by
0.5 (adjusted b =
0.55; 95% confidence interval [CI], -0.99 to -0.10; p <
0.05; Table 3). Therefore, frequency of psychiatric
admission accounted for 9% of the MARS total score
variance (r2 =
0.09).
The relationships of social support, insight, and
psychopathology with medication adherence were explored
by regression analysis. The relationships were examined
using SLR, followed by MLR. All the variables that met
the initial screening criteria (p < 0.25) were entered into
MLR. After controlling for insight, the MLR analysis

Medication Adherence in Schizophrenia

showed a significant negative linear relationship between


psychopathology and total MARS score. Increase in the
total BPRS by 1 reduced the MARS total score by 0.13

Table 1. Demographic characteristics of outpatients with schizophrenia and relapse cases. *


Measure

Relapse cases (n = 35) Outpatients (n = 35)

X2 / t

p Value

Mean standard deviation age (years)

33 10

33 8

-0.047

0.91

Sex
Male
Female

21 (60)
14 (40)

19 (54)
16 (46)

0.23

0.63

Education level
Primary
Secondary
Tertiary

4 (11)
19 (54)
12 (34)

1 (3)
25 (71)
9 (26)

3.05

0.22

Marital status
Single
Married
Divorced / separated

23 (66)
4 (11)
8 (23)

21 (60)
11 (31)
3 (9)

5.63

0.06

Occupation
Unemployed
Employed

24 (69)
11 (31)

17 (49)
18 (51)

2.88

0.08

Personal income (Malaysian ringgit)


< 100
101-500
501-1000
> 1000

21 (60)
6 (17)
4 (11)
4 (11)

17 (49)
4 (11)
6 (17)
8 (23)

2.55

0.46

Duration of illness (years)


1-5
6-10
> 10

14 (40)
5 (14)
16 (46)

11 (31)
9 (26)
15 (43)

1.53

0.46

Frequency of admission (times)


None
1-5
>5

0
17 (49)
18 (51)

12 (34)
20 (57)
3 (9)

22.95

< 0.05

Type of antipsychotics
Typical
Atypical
Both

11 (31)
20 (57)
4 (11)

9 (26)
25 (71)
1 (3)

2.55

0.27

Data are shown as No. (%) of patients, unless otherwise specified.


Independent t test.

Table 2. Comparison between outpatients with schizophrenia and relapse cases. *


Measure

Relapse cases

Outpatients

MARS
MSPSS
ITAQ
Symptoms
BPRS (total)
BPRS (psychotic)
BPRS (depressive)

2.6 1.2
53.0 15.3
7.6 6.0

2.0 1.5
62.7 12.6
9.3 5.1

5.3 1.0
5.3 1.0
0

0.1 0.3
0
0.1 0.3

Mean difference
(95% CI)
-0.9 to 1.2
3.0 to -16.4
-0.9 to 4.4
-5.6 to -4.9
-5.7 to -5.0
-0.01 to 0.18

p Value

1.70
2.90
1.295

0.09
< 0.05
0.20

-29.96
-31.66
1.78

< 0.05
< 0.05
0.08

Abbreviations: BPRS = Brief Psychiatric Rating Scale; CI = confidence interval; ITAQ = Insight and Treatment Attitude
Questionnaire; MARS = Medication Adherence Rating Scale; MSPSS = Multidimensional Scale of Perceived Social Support.
*
Data are shown as mean standard deviation, unless otherwise specified.

Independent t test.
East Asian Arch Psychiatry 2014, Vol 24, No.2

71
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(adjusted b = 0.12; 95% CI, -0.24 to -0.01; p < 0.05;


Table
4). Therefore, the severity of schizophrenic symptoms
accounted for 8% of the MARS total score variance (r2 =
0.08).

Discussion
This study found a high non-adherence rate in the study
subjects, with nearly half of all the patients (51%) not
adhering to their medication. As expected, the nonadherence rate among patients with relapse schizophrenia
(61%) was higher than that in outpatients with
schizophrenia (39%), although the difference in the rate
was not significant. Better social support and insight in
outpatients with schizophrenia partly contributed to their
higher rate of adherence. The non-adherence rate in this
study aligns with that from other studies, such as those by
Lacro et al16 (49.5%) and Yang et al17 (41.2%). However,
one study18 found that the rate of non-compliance with
medication was as low as 25.8%.
The poor medication adherence in both groups of

patients with schizophrenia in this study is contributed


by several local factors, which were not explored in this
study. These include subcultural beliefs about mental
illness, the interference of Malay traditional healers
(Bomoh), and stigmatisation of mental illness. A significant
number of psychiatric patients in this country stop taking
their medications after visiting traditional healers.19 The
stigma towards patients with schizophrenia in developing
countries such as Malaysia is also high; it is associated with
workplace difficulties, family rejection, follow-up default,
and treatment non-adherence.20 A local study21 found that
such stigma creates a barrier to modern psychiatric care as
the majority of patients prefer traditional treatment.
Recent studies22-24 show that non-adherence to
medication was a common factor which predicted the
relapse of patents with schizophrenia. On average, nonadherent patients have a 3.7 times greater risk of relapse
than patients who adhere to treatment. 25 Complete
discontinuation of medication is believed to cause about 1
in 10 hospital admissions and 1 in 5 nursing home
admissions.26 A local

Table 3. Association between demographic factors with medication adherence among patients with schizophrenia.*

Age
Gender
Education level
Marital status
Occupation
Income
Duration of illness
Frequency of admission
Type of antipsychotic

Simple linear regression


crude regression coefficient
(95% CI)

p Value

-0.03 (-0.07 to 0.003)

0.08

-0.80
-0.19
-0.13
-0.32
-0.007
-0.23
0.59
0.08

(-1.43
(-0.76
(-0.56
(-0.97
(-0.28
(-0.59
(-1.05
(-0.49

to
to
to
to
to
to
to
to

-0.18)
0.38)
0.30)
0.33)
0.27)
0.12)
-0.13)
0.66)

0.01
0.51
0.54
0.32
0.95
0.19
0.01
0.76

Multiple linear regression


adjusted regression
coefficient (95% CI)

p Value

-0.55 (-0.99 to -0.10)

< 0.05

Abbreviation: CI = confidence interval.


*
Forward, backward, and stepwise regression methods were applied. Model assumption was fulfilled. There were no interactions
among dependent variables. No multicollinearity was detected. Coefficient of determination (r2) = 0.09.

Table 4. Association of symptoms, insight, and social support with medication adherence among patients with
schizophrenia.*
Variable

Simple linear regression


Crude regression coefficient
(95% CI)

MSPSS
BPRS
ITAQ

2.21 (0.89-3.52)
-0.13 (-0.24 to -0.02)
0.04 (-0.02 to 0.09)

Multiple linear regression

p Value

Adjusted regression
coefficient (95% CI)

p Value

-0.12 (-0.24 to -0.01)

< 0.05

0.85
< 0.05
0.19

Abbreviations: BPRS = Brief Psychiatric Rating Scale; CI = confidence interval; ITAQ = Insight and Treatment Attitude
Questionnaire; MSPSS = Multidimensional Scale of Perceived Social Support.
*
Forward, backward and stepwise multiple linear regression methods were applied. Model assumption was fulfilled. No
East Asian Arch Psychiatry 2014, Vol 24, No.2
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multicollinearity was detected. Coefficient of determination (r2) = 0.08.

East Asian Arch Psychiatry 2014, Vol 24, No.2

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73

study by Ng et al27 reported that 32.2% of patients who


were readmitted to the psychiatric ward of a teaching
hospital within 6 months after discharge returned as a result
of poor adherence to medication. Poor adherence to
medication is the most important factor related to early
readmission in patients with psychotic disorders.
Among the socio-demographic variables, only
frequency of admission showed a significant difference
between the 2 groups; patients with relapse schizophrenia
had higher frequency of admission than the outpatients.
This finding is in agreement with that from a previous
study28 which showed that the number of previous
admissions and prescription of multiple antipsychotics
were associated with frequent relapse. A local study by
Draman et al29 also found that the number of previous
admissions was one of the significant risk factors for
repeat admissions. It has also been reported that the
majority of patients with multiple admissions due to nonadherence to antipsychotic medication early in the
treatment is less likely to be adherent later.22 This is in
concordance with our finding that the majority of patients
with relapse schizophrenia was admitted more than 5 times
in the past.
We found that perceived social support was
significantly better in outpatients with schizophrenia than
patients with relapse schizophrenia. If patients perceived
that they were getting adequate social support, the rate
of medication adherence was relatively elevated as seen
in the outpatient group. Therefore, improving patients
perceptions of adequate social support might improve
medication adherence. This finding was in concordance
with the study by Hudson et al30 in which lack of social
support and supervision commonly contributed to poor
treatment adherence. The medication non-adherence
eventually translated to multiple relapses and admissions.
Generally, 50% of patients with schizophrenia have
poor insight.31 Their ability to recognise their schizophrenic
experiences and label them pathological would improve
their insight. This awareness might convince them that they
have a mental illness that could benefit from treatment.
This, in turn, may lead to improved medication adherence.
This hypothesis is supported by other studies 32,33 which
showed that lack of insight was correlated with poor
medication adherence, and a study by Tsang et al34 in
which insight was the strongest predictor of medication
adherence. However, no
statistically
significant
relationship was found between insight and treatment
adherence in this study, although insight was slightly better
in outpatients with schizophrenia versus those with
relapse. A possible explanation for the non-significant
finding might be confounding factors such as duration of
illness and chronicity.35 Almost half of the patients in both
groups had suffered from schizophrenia for
> 10 years. Motivational problems as part of the chronicity
of the illness have been cited by Weiden et al36; these
will influence clinical attendance rates and adherence to
prescribed regimens.
Overall, the relapse patients had significantly more

severe psychotic symptoms, with higher mean BPRS score,

than the outpatients with schizophrenia. There was also


a significant relationship between psychopathology and
medication adherence. Patients who had severe psychotic
symptoms showed poor medication adherence. It has been
shown that the severity of acute psychotic symptoms such
as persecutory delusions, hostility, grandiosity, perplexity,
and thought disorder is associated with treatment
refusal.37,38
It makes sense that those with acute psychotic symptoms
of the persecutory variety will be suspicious of treatment
or believe that they are being poisoned or punished. Those
with grandiosity are unlikely to interpret their mental state
as an illness requiring treatment. A recent study by Yang
et al17 also found that the severity of disease was closely
related with medication adherence. Medication adherence
would be poor if patients had more severe
psychopathology.
We concluded that if adherence could be addressed
appropriately, the number of admissions and severity of
psychopathology could be improved, leading to better
patient outcomes. In a recent systematic review, Hayness et
al39 concluded that current methods of improving adherence
for chronic health problems are mostly complex and not
very effective, so the full benefits of treatment cannot be
realised. In order to improve adherence, the intervention
should comprise multiple strategies such as a combination
of educational, behavioural, and cognitive strategies.8 The
non-adherence rate could also be effectively reduced if
simple measures such as prescribing a simple dose regimen
(drug dosing not exceeding more than twice per day) and
counselling the patients to enhance treatment adherence
were implemented routinely in clinical practice.40
This study had several limitations. It was a crosssectional study with a small sample size; thus, causeeffect relationship could not be determined. A simple
method was used to measure medication adherence; a
self-rating scale with only 4 items was administered. It is
not objective enough to reflect the real picture as we know
that medication adherence is a complex issue. There were
several other confounding factors which were not assessed
such as severity of negative symptoms, side-effects of the
medications, complexity of medicine regimens prescribed,
and the distance from hospital to home. The sample
consisted of a heterogeneous group of patients with regard
to chronicity and duration of illness. It is better to limit the
duration of the illness to reduce the confounding factors
associated with it. Furthermore, more than 90% of the
sample comprised Malay patients who did not represent the
multiracial society of the country.

Declaration
The authors declared no conflict of interest. The study was
self-supported for preparation of dissertation of MMed
(Psychiatry), Universiti Sains Malaysia.

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