O R I G I N A L P A P E R
Quality of Life in Patients with Schizophrenia:
The Impact of Socio-economic Factors and Adverse
Effects of Atypical Antipsychotics Drugs
Aurigena Antunes de Arau´jo
•Diego de Arau´jo Dantas
•Gemma Galgani do Nascimento
•Susana Barbosa Ribeiro
•Katarina Melo Chaves
•Vanessa de Lima Silva
•Raimundo Fernandes de Arau´jo Jr.
•Dyego Leandro Bezerra de Souza
•Caroline Addison Carvalho Xavier de Medeiros
Published online: 1 May 2014
Ó Springer Science+Business Media New York 2014
Abstract
This cross-sectional study compared the effects of treatment with atypical
anti-psychotic drugs on quality of life (QoL) and side effects in 218 patients with schizophrenia
attending the ambulatory services of psychiatric in Rio Grande do Norte, Brazil.
Socio-eco-nomic variables were compared. The five-dimension EuroQoL (EQ-5D) was used to evaluate
QoL, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side
Effect Rating Scale and the Simpson–Angus Scale. Data were analysed using the v
2test and
Aurigena Antunes de Arau´jo and Diego de Arau´jo Dantas have showed the same importance for carrying out the work.
A. A. de Arau´jo (&) C. A. C. X. de Medeiros
Department of Biophysical and Pharmacology, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil
e-mail: aurigena@ufrnet.br C. A. C. X. de Medeiros
e-mail: carolineaddisonfarma@yahoo.com.br A. A. de Arau´jo S. B. Ribeiro K. M. Chaves
Post Graduation Program of Pharmaceutical Science, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil
e-mail: susabarbosa@hotmail.com K. M. Chaves
e-mail: katarina_chaves@yahoo.com.br A. A. de Arau´jo D. L. B. de Souza
Post Graduation Program Public Health, UFRN, Natal, RN, Brazil e-mail: dysouz@yahoo.com.br
D. de Arau´jo Dantas
Department of the Post Graduation Program in Health and Society/UERN, UERN, Natal, RN, Brazil e-mail: diegoaraujodantas@gmail.com
G. G. do Nascimento
Department of Nursing, UERN, Mossoro´, RN, Brazil DOI 10.1007/s11126-014-9290-x
Student’s t test, with a significance level of 5 %. Average monthly household incomes in the
medication groups were 1.1–2.1 minimum wages ($339–$678). UKU Scale scores showed
significant differences in side effects, mainly, clozapine, quetiapine and ziprasidone (p \ 0.05).
EQ-5D scores showed that all drugs except olanzapine significantly impacted mobility
(p \ 0.05), and proportions of individuals reporting problems in other dimensions were high:
63.6 % of clozapine users reported mobility problems, 63.7 and 56.3 % of clozapine and
ziprasidone users, respectively, had difficulties with usual activities, 68.8 and 54.5 % of
zipr-asidone and clozapine users, respectively, experienced pain and/or discomfort, and 72.8 % of
clozapine users reported anxiety and/or depression. Psychiatric, neurological, and autonomous
adverse effects, as well as other side effects, were prevalent in users of atypical antipsychotic
drugs, especially clozapine and ziprasidone. Olanzapine had the least side effects. QoL was
impacted by side effects and economic conditions in all groups. Thus, the effects of these
antipsychotic agents appear to have been masked by aggravating social and economic situations.
Keywords
Schizophrenia
Atypical antipsychotic Quality of life
Introduction
Schizophrenia is a significantly disabling disease that affects all major areas of life [
1
], it
has been demonstrated consistently to have a major negative impact on quality of life, QoL
[
2
–
5
]. Numerous factors can affect QoL in patients with schizophrenia, including
socio-demographic factors [
6
,
7
], symptomatological patterns of the disease [
8
–
11
], and side
effects of antipsychotic medication [
12
,
13
].
Fujimaki et al. [
14
] found that chronic treatment with typical antipsychotic drugs had
stronger negative effects on QoL than did treatment with atypical antipsychotic
medica-tions due to the greater incidence of side effects involving extrapyramidal symptoms.
Similarly, Fang et al. [
15
] evaluated the effects of seven antipsychotic medications
(chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, and
aripipraz-ole), and found that atypical antipsychotic drugs, especially olanzapine and quetiapine,
were superior to typical antipsychotics in improving schizophrenic patients’ QoL. In
contrast, Chaves et al. [
16
] reported that patients taking risperidone and olanzapine had
impaired or very impaired QoL, and that the effects of these antipsychotic agents appear to
have been masked by aggravating social and economic situations.
Cascade et al. [
17
] showed that approximately 54 % of 353 respondents reported
experiencing side effects of atypical antipsychotic medication. The most common side
effects were weight gain, hunger, fatigue/lethargy, lack of coordination, and muscle
problems (e.g. tenderness, twitches, and tremors) [
17
].
V. de Lima Silva
Department of Pharmaceutical Science, UFRN, Natal, RN, Brazil e-mail: vanessaslv702@gmail.com
R. F. de Arau´jo Jr.
Department of Morphology, Post Graduation Program in Functional and Structural Biology/Post Graduation Program Health Science, UFRN, Natal, RN, Brazil
e-mail: araujojr@cb.ufrn.br C. A. C. X. de Medeiros
In Brazil, although advances have been made in access to and choice of therapy for
schizophrenia, few studies have examined the potential risks, side effects, and impact on
QoL compared with second-generation antipsychotic drugs [
16
,
18
–
20
]. The assessment of
health-related QoL is essential because this parameter interferes with the choice of
treat-ment; the results of such evaluation may provide a starting point for ambulatory services
and rehabilitation. The five-dimension EuroQoL (EQ-5D) has been used to assess QoL in
patients with chronic disease. This generic instrument evaluates all important
health-related aspects and the impact of the disease on the individual. In this study, we used the
EQ-5D to assess the impact of atypical antipsychotic use on QoL in patients with
schizophrenia and evaluated the adverse effects of this treatment.
Materials and Methods
This cross-sectional study was conducted at the Dr. Joa˜o Machado (Natal, RN, Brazil) and
Sa˜o Camilo (Mossoro´, RN, Brazil) hospitals, and the Centre for Psychosocial Care Arte de
Viver (Caico´, RN, Brazil). Adult patients (aged [18 years) diagnosed with schizophrenia
according to the International Classification of Diseases 10 and Diagnostic and Statistical
Manual of Mental Disorders IV criteria [
21
] who had received treatment with a
second-generation atypical antipsychotic drug for C1 year were considered for inclusion in the
study. Individuals \18 years old were excluded of the study. Participants and their family
members provided written informed consent (protocol number 71235-CEP/UERN). The
study was conducted in accord with the Declaration of Helsinki [
22
].
Sample Size Calculation
In 2012, 5,000 patients of the ambulatory services of the participating institutions received
atypical antipsychotic drugs (olanzapine, 34 %; risperidone, 33 %; ziprasidone, 13 %;
clozapine, 10 %; quetiapine, 10 %). To calculate the appropriate sample size, we used a
95 % confidence interval and a 10 % tolerable sampling error. Considering the finite
population and the prevalence of risperidone use (among antipsychotics atypical: lower
cost), the following formula was used:
n
¼
z
2 a=2NPð1 PÞ
e
2ðN 1Þ þ z
2 a=2Pð1 PÞ
;
where n is the sample size, z
a/2is the confidence interval, P is the prevalence, N is the
population, and e is the tolerable sampling error. The calculated sample size was 218
patients: 156 in Natal, 41 in Mossoro´, and 21 in Caico´.
Data Collection
Economic and socio-demographic variables (age, sex, employment, household income,
years of education, social security) were assessed using a structured questionnaire.
Adverse events related to antipsychotic drug use were assessed using the Udvalg for
Kliniske Undersøgelser (UKU) Side Effect Rating Scale [
23
], which rates symptom
severity and the perception or assessment that a symptom is a side effect. The UKU Scale
is divided into four sections: psychiatric symptoms (10 items), neurological symptoms (8
items), autonomic symptoms (11 items), and other effects (19 items). The severity of each
item is rated on a scale ranging from 0 to 3. The Simpson–Angus Scale, was developed in
1970 for the assessment of drug-induced parkinsonism and related extrapyramidal side
effects [
24
]. This scale has demonstrated clinical validity and a high degree of inter-rater
reliability. It comprises 10 items measuring rigidity (6 items), gait (hypokinesia), glabellar
reflex, tremor, and salivation (1 item each). Each item is scored on a five-point scale
ranging from 0 to 4. The total score is the sum of items divided by 10, with a total score
[0.3 indicating the presence of extrapyramidal symptoms [
25
].
QoL was assessed using the EQ-5D administered by interview, which evaluates 5Ds of
health (mobility, self-help, habitual activities, pain, anxiety/depression) on a three-point
scale ranging from 1 to 3. Item scores were dichotomised as ‘no problem’ (score = 1) or
‘problems’ (score = 2–3) to profile the frequencies of reported problems. The EQ-5D has
been validated in Brazil [
26
].
Data Analysis
Socio-economic, socio-demographic, and clinical variables were compared among atypical
antipsychotic groups using the v
2test and analysis of variance (ANOVA). EQ-5D, UKU
Side Effect, and Simpson–Angus Scale scores were compared using ANOVA. A p value
\0.05 was considered significant.
Results
The demographic characteristics of the study participants are shown in Table
1
.
Signifi-cantly more men than women used antipsychotic drugs (p = 0.03). Average monthly
household incomes in the medication groups were 1.1–2.1 minimum wages ($339–$678),
and participants had low educational levels (B8 years in 80.8–100 % of individuals). The
majority (69.2–90.3 %) of individuals were unemployed and 30.8–50 % received no social
security. These characteristics did not differ significantly among groups.
Global score of Simpson–Angus Scale greater than 0.3 was observed for users of
risperidone, quetiapine and clozapine (Table
2
). Significant differences in UKU Side
Effect Rating Scale scores were observed for the following items: memory difficulties
(ziprasidone vs. quetiapine, p = 0.02), tension/restlessness (ziprasidone vs. quetiapine,
p = 0.03), tremor (ziprasidone vs. risperidone, olanzapine, p = 0.01), epileptic seizures
(clozapine/quetiapine vs. olanzapine/risperidone/ziprasidone, p \ 0.00), increased
saliva-tion (quetiapine vs. ziprasidone, p = 0.03), orthostatic dizziness (risperidone vs.
olanza-pine, p = 0.01), increased tendency to sweat (quetiapine vs. ziprasidone, p \ 0.00), rash
(risperidone vs. olanzapine, p = 0.04), weight gain (quetiapine vs. ziprasidone, p = 0.05),
galactorrhea (risperidone vs. olanzapine, ziprasidone, quetiapine, clozapine, p = 0.04),
increased sexual desire (quetiapine vs. olanzapine, p = 0.031), decreased sexual desire
(quetiapine vs. olanzapine, p \ 0.01), erectile dysfunction (quetiapine vs. olanzapine,
p = 0.02; Table
3
) and orgasmic dysfunction (quetiapine vs. olanzapine, p = 0.01).
High percentages of antipsychotic drug users reported difficulties in several EQ-5D
dimensions that affected QoL (Fig.
1
). Mobility was significantly impaired by all
medi-cations except olanzapine (risperidone and clozapine, p \ 0.001; ziprasidone, p \ 0.01;
quetiapine, p \ 0.05). No difference among medications was observed in the other
dimensions, but many individuals reported problems. 63.6 % of clozapine users reported
mobility problems, 63.7 and 56.3 % of clozapine and ziprasidone users, respectively, had
difficulties with usual activities, 68.8 and 54.5 % of ziprasidone and clozapine users,
respectively, experienced pain and/or discomfort, and 72.8 % of clozapine users reported
anxiety and/or depression.
Discussion
The introduction of second-generation antipsychotic medications brought the promise of
improved QoL for patients with schizophrenia, which has been confirmed in several studies
[
14
,
27
–
29
]. Conversely, high percentages of individuals in the present study reported
Table 1 Sociodemographic variables of patients with schizophrenia taking antipsychotic drugs (RN, Brazil, 2014) Characteristic Olanzapine (n = 76) Risperidone (n = 72) Ziprasidone (n = 23) Quetiapine (n = 26) Clozapine (n = 13) p Age (years) 39.0 ± 12.7 41.7 ± 12.1 38.4 ± 11.8 39.3 ± 12.1 35.5 ± 7.6 0.194 Household incomea 1.7 ± 1.3 1.9 ± 1.6 2.1 ± 1.0 1.8 ± 2.0 1.1 ± 0.6 0.780 Sex Male (%) 73.7 52.8 43.5 57.7 69.2 0.031* Female (%) 26.3 47.2 56.5 42.3 30.8 Years of education B8 (%) 91.9 95.8 91.3 80.8 100.0 0.730 [8 (%) 8.1 4.2 8.7 19.2 0.0 Employment Yes (%) 12.2 9.7 13.0 30.8 15.4 0.114 No (%) 87.8 90.3 87.0 69.2 84.6 Social security Yes (%) 62.7 52.8 60.9 50.0 69.2 0.573 No (%) 37.3 47.2 39.1 50.0 30.8
* Significant difference between groups a
Minimum wage in Brazil in March 2012
Table 2 Mean Simpson–Angus Scale scores, Natal, RN, 2014
Items Olanzapine Risperidone Ziprasidone Quetiapine Clozapine p
Gait 0.3 0.5 0.4 0.5 0.8 0.14 Arm dropping 0.5 0.5 0.4 0.5 0.6 0.91 Shoulder shaking 0.4 0.3 0.2 0.4 0.5 0.79 Elbow rigidity 0.2 0.4 0.3 0.3 0.6 0.42 Wrist rigidity 0.4 0.4 0.1 0.4 0.5 0.48 Leg pendulousness 0.3 0.4 0.4 0.3 0.3 0.90 Head dropping 0.1 0.2 0.2 0.3 0.4 0.49 Glabellar reflex 0.2 0.3 0.1 0.1 0.5 0.16 Tremor 0.4 0.4 0.7 0.6 0.5 0.49 Salivation 0.4 0.4 0.1 0.8 0.7 0.02* Total score 0.3 0.4 0.3 0.4 0.5 0.28
Table 3 Mean UKU Side Effect Rating Scale scores, Natal, RN, Brazil, 2014
Items Olanzapine Risperidone Ziprasidone Quetiapine Clozapine p Psychiatric side effects
Difficulty concentrating 0.9 1.2 1.4 0.5 1.3 0.090 Asthenia/lassitude/fatigue 1.0 1.2 1.0 1.0 0.6 0.383 Somnolence/sedation 0.8 1.2 1.3 0.8 0.7 0.073 Memory difficulties 1.0 1.3 1.7* 0.8a 1.2 0.022* Depression 1.1 1.1 1.3 1.1 0.8 0.751 Tension/restlessness 0.8 1.0 1.5* 0.7a 1.2 0.028*
Increased sleep duration 0.8 0.9 1.3 1.0 0.6 0.224
Decreased sleep duration 0.2 0.2 0.3 0.2 0.2 0.914
Increased dream activity 0.4 0.7 0.9 0.6 0.5 0.067
Emotional indifference 0.5 0.6 0.4 0.6 0.8 0.684
Neurological side effects
Dystonia 0.3 0.4 0.4 0.5 0.3 0.266 Rigidity 0.4 0.5 0.3 0.5 0.5 0.802 Hypokinesia/akinesia 0.2 0.3 0.1 0.4 0.4 0.176 Hyperkinesis 0.1 0.2 0.3 0.2 0.3 0.194 Tremor 0.5a 0.6a 1.2* 0.8 1.0 0.012* Akathisia 0.3 0.4 0.3 0.6 0.6 0.304 Epileptic seizures 0.2a 0.2a 0.0a 0.5* 0.8* 0.000* Paresthesia 0.3 0.4 0.5 0.5 0.1 0.188
Autonomic side effects Change in visual accommodation 0.4 0.5 0.7 0.7 0.7 0.409 Increased salivation 0.4 0.6 0.3a 0.9* 1.0 0.027 Decreased salivation 0.3 0.4 0.2 0.1 0.0 0.109 Nausea/vomiting 0.3 0.4 0.3 0.4 0.4 0.872 Diarrhoea 0.1 0.2 0.1 0.4 0.2 0.077 Constipation 0.2 0.3 0.5 0.2 0.3 0.218 Voiding disorders 0.2 0.1 0.0 0.3 0.1 0.391 Polyuria/polydipsia 0.4 0.5 0.7 1.0 0.8 0.073 Orthostatic dizziness 0.2a 0.5* 0.1 0.5 0.5 0.012* Palpitations/tachycardia 0.4 0.6 0.5 0.4 0.5 0.685 Increased tendency to sweat 0.4 0.5 0.0a 0.8* 0.6 0.007*
Other side effects
Rash 0.0a 0.2* 0.0 0.1 0.1 0.037* Rash, morbilliform 0.0 0.0 0.0 0.0 0.0 0.533 Rash, petechial 0.0 0.0 0.0 0.1 0.0 0.398 Rash, urticarial 0.0 0.0 0.0 0.0 0.0 0.990 Rash, psoriatic 0.0 0.0 0.0 0.0 0.0 0.728 Rash (unclassified) 0.0 0.0 0.0 0.0 0.1 0.559 Itchiness 0.2 0.3 0.1 0.5 0.3 0.242 Photosensitivity 0.3 0.5 0.3 0.6 0.7 0.269 Increased pigmentation 0.1 0.1 0.1 0.1 0.0 0.627
difficulties in 5Ds of QoL associated with the compromised ability to perform daily
activities. These findings are consistent with those of a previous study conducted in Brazil
[
16
], which showed significantly reduced QoL among patients with schizophrenia who
used olanzapine and risperidone and no benefit associated with the use of
second-gener-ation antipsychotic drugs due to poor socio-economic conditions. This inconsistency in
results may be related to socio-economic differences among patient groups that directly
affect QoL. Users of atypical antipsychotic drugs in the present study lived in poor
socio-economic conditions, as reflected by low household incomes, low educational level, social
security.
In Brazil, improved access to care and therapeutic options have resulted in a shift from the
treatment of schizophrenia and other mental illnesses. The Mental HealthCare Reform (2001)
and Centres for Psychosocial Care reflect a policy of social inclusion for people with mental
illnesses [
30
]. Other policies adopted by the Brazilian government have improved access to
antipsychotic medication for the mentally ill; for example, the Specialised Programme for
Pharmaceutical Assistance, part of the national health system, was created to ensure the
completeness of drug treatment in outpatients whose care is defined in Therapeutic
Guide-lines and Clinical Protocols [
31
]. In addition, Ordinance 364 (clinical therapy guideline—
schizophrenia) stipulates that all antipsychotic drugs except clozapine may be used in the
treatment of schizophrenia, with no order of preference [
32
]. However, the results of this
study suggest that the Brazilian governments’ subsidy of second-generation antipsychotic
drugs and related measures have not had the expected impact on users’ QoL.
In addition to aggravating social conditions, the side effects of atypical antipsychotic
medications impacted users’ QoL in the present study. For example, the side effects of
Table 3 continued
Items Olanzapine Risperidone Ziprasidone Quetiapine Clozapine p
Weight gain 1.3 1.4 1.0a 2.0* 1.2 0.050* Weight loss 0.2 0.4 0.4 0.0 0.2 0.124 Menorrhagia 0.0 0.3 0.2 0.3 0.3 0.554 Amenorrhea 0.3 0.3 0.3 0.3 0.3 0.999 Galactorrhea 0.0a 0.3* 0.0a 0.0a 0.0a 0.041* Gynecomastia 0.1 0.1 0.0 0.3 0.2 0.311
Increased sexual desire 0.1a 0.2 0.0 0.4* 0.0 0.026*
Decreased sexual desire 0.2a 0.6 0.2a 1.0* 0.4 0.007*
Erectile dysfunction 0.0a 0.2 0.1 0.4* 0.0 0.016* Ejaculatory dysfunction 0.1 0.2 0.1 0.3 0.0 0.487 Orgasmic dysfunction 0.0a 0.3 0.0 0.4* 0.0 0.007* Vaginal dryness 0.1 0.6 0.3 0.5 0.0 0.139 Headache 0.5 0.7 0.7 1.0 0.8 0.147 Tension 0.3 0.4 0.2 0.7 0.5 0.128 Migraine 0.3 0.2 0.1 0.4 0.5 0.335 Other 0.1 0.2 0.2 0.3 0.3 0.261 Physical dependence 0.8 0.7 1.1 0.8 0.9 0.749 Psychic dependence 1.0 1.1 1.2 1.0 1.5 0.652
* Significant difference among groups a
ziprasidone (memory difficulties and tension/restlessness) and clozapine (epileptic
sei-zures) measured by the UKU Scale, as well as the total score of Simpson–Angus Scale for
clozapine, may have impacted the dimension of anxiety/depression, pain/discomfort and
usual activities. Only olanzapine did not affect mobility and resulted in no significant side
effect. Corroborating this result, several authors have shown the superiority of olanzapine
over other atypical antipsychotic drugs with respect to QoL [
33
,
34
].
Thus, the use of second-generation antipsychotic drugs, particularly ziprasidone and
clozapine, is associated with adverse effects, which in combination with poor living
conditions may affect users’ QoL. These findings suggest that anything impact a the
introduction of next-generation drugs for patients living in poor socio-economic
conditions.
Conclusion
We found that psychiatric, neurological, and autonomous adverse effects, as well as other
side effects, were prevalent among users of second-generation antipsychotic drugs,
espe-cially ziprasidone and clozapine. Olanzapine was associated with few side effects,
although all antipsychotic drugs were related to mobility problems. Many patients had low
household incomes and were unemployed, thus, the effects of these antipsychotic agents
appear to have been masked by aggravating social and economic situations.
Fig. 1 Proportions of individuals reporting level 2/3 problems in EQ-5D dimensions, Natal, RN, Brazil, 2013
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Aurigena Antunes de Arau´jois a professor of Department of Biophysical and Pharmacology and Post graduation program Public Health/Post graduation program Pharmaceutical Science, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil. Her research interests are mental health services research, health economics, pharmacokinetics and experimental pharmacology.
Diego de Arau´jo Dantasis a student of the Post graduation program in Health and Society (UERN), Mossoro´, RN, Brazil.
Gemma Galgani do Nascimentois a student of Nursing, UERN, Mossoro´, RN, Brazil.
Susana Barbosa Ribeirois a Post graduation program of Pharmaceutical Science, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil.
Katarina Melo Chaves Ms in Pharmaceutical Science, Post-graduation in Pharmaceutical Science, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Vanessa de Lima Silvais a student of graduation of Pharmaceutical Science, UFRN, Natal, RN, Brazil.
Raimundo Fernandes de Arau´jo Jr.is a professor of Department of Morphology and Post graduation program in Functional and Structural Biology/Post graduation program Health Science, UFRN, Natal, RN, Brazil. His research interests are cell line cancer and experimental pharmacology.
Dyego Leandro Bezerra de Souzais a professor of Department public health and Post graduation program Public Health, UFRN, Natal, RN, Brazil. His research interests are public health and epidemiology.
Caroline Addison Carvalho Xavier de Medeiros is a professor of Department of Biophysical and Pharmacology, Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN, Brazil and Post graduation program in Health and Society (UERN), Mossoro´, RN, Brazil. Her research interests are mental health services research and experimental pharmacology.