Psychiatr Q DOI 10.1007/s11126-014-9290-x ORIGINAL PAPER
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
•
Ó Springer Science+Business Media New York 2014
Abstract This cross-sectional study compared the effects of treatment with atypical antipsychotic 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-economic 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 v2 test 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: [email protected] C. A. C. X. de Medeiros e-mail: [email protected] 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: [email protected] K. M. Chaves e-mail: [email protected] A. A. de Arau´jo D. L. B. de Souza Post Graduation Program Public Health, UFRN, Natal, RN, Brazil e-mail: [email protected] D. de Arau´jo Dantas Department of the Post Graduation Program in Health and Society/UERN, UERN, Natal, RN, Brazil e-mail: [email protected] G. G. do Nascimento Department of Nursing, UERN, Mossoro´, RN, Brazil e-mail: [email protected]
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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 ziprasidone 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 sociodemographic 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 medications 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 aripiprazole), 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: [email protected] 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: [email protected] C. A. C. X. de Medeiros Post Graduation Program in Health and Society (UERN), Mossoro´, RN, Brazil
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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 treatment; 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 healthrelated 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 secondgeneration 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: n¼
z2a=2 NPð1 PÞ e2 ðN 1Þ þ z2a=2 Pð1 PÞ
;
where n is the sample size, za/2 is 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
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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 v2 test 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. Significantly 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 salivation (quetiapine vs. ziprasidone, p = 0.03), orthostatic dizziness (risperidone vs. olanzapine, 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 medications 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,
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Psychiatr Q 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
Male (%)
73.7
52.8
43.5
57.7
69.2
0.031*
Female (%)
26.3
47.2
56.5
42.3
30.8
Sex
Years of education B8 (%)
91.9
95.8
91.3
80.8
100.0
[8 (%)
8.1
4.2
8.7
19.2
0.0
0.730
Employment Yes (%)
12.2
9.7
13.0
30.8
15.4
No (%)
87.8
90.3
87.0
69.2
84.6
0.114
Social security Yes (%)
62.7
52.8
60.9
50.0
69.2
No (%)
37.3
47.2
39.1
50.0
30.8
0.573
* 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
* Significant difference among groups
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
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Psychiatr Q 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
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
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
Neurological side effects
Autonomic side effects
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*
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
Other side effects
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Psychiatr Q 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
Group compared
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-generation 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 socioeconomic 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 Guidelines 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
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Fig. 1 Proportions of individuals reporting level 2/3 problems in EQ-5D dimensions, Natal, RN, Brazil, 2013
ziprasidone (memory difficulties and tension/restlessness) and clozapine (epileptic seizures) 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, especially 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.
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References 1. Switaj P, Anczewska M, Chrostek A, Sabariego C, Cieza A, Bickenbach J, et al.: Disability and schizophrenia: A systematic review of experienced psychosocial difficulties. BMC Psychiatry 12:193, 2012. 2. Adelufosi AO, Ogunwale A, Abayomi O, Mosanya JT: Socio-demographic and clinical correlates of subjective quality of life among Nigerian outpatients with schizophrenia. Psychiatry Research 209(3):320–325, 2013 (Epub 5 Mar 2013). 3. Xiang YT, Weng YZ, Leung CM, Tang WK, Ungvari GS: Subjective quality of life in outpatients with schizophrenia in Hong Kong and Beijing: Relationship to socio-demographic and clinical factors. Quality of Life Research 17(1):27–36, 2008 (Epub 24 Nov 2007). 4. Xiang YT, Wang CY, Wang Y, Chiu HF, Zhao JP, Chen Q, et al.: Socio-demographic and clinical determinants of quality of life in Chinese patients with schizophrenia: A prospective study. Quality of Life Research 19(3):317–322, 2010 (Epub 6 Feb 2010). 5. Wetherell JL, Palmer BW, Thorp SR, Patterson TL, Golshan S, Jeste DV: Anxiety symptoms and quality of life in middle-aged and older outpatients with schizophrenia and schizoaffective disorder. The Journal of Clinical Psychiatry 64(12):1476–1482, 2003. 6. Hsiao CY, Hsieh MH, Tseng CJ, Chien SH, Chang CC: Quality of life of individuals with schizophrenia living in the community: Relationship to socio-demographic, clinical and psychosocial characteristics. Journal of Clinical Nursing 21(15–16):2367–2376, 2012 (Epub 14 June 2012). 7. Caron J, Mercier C, Diaz P, Martin A: Socio-demographic and clinical predictors of quality of life in patients with schizophrenia or schizo-affective disorder. Psychiatry Research 137(3):203–213, 2005 (Epub 22 Nov 2005). 8. Rocca P, Giugiario M, Montemagni C, Rigazzi C, Rocca G, Bogetto F: Quality of life and psychopathology during the course of schizophrenia. Comprehensive Psychiatry 50(6):542–548, 2009. 9. Chugh PK, Rehan HS, Unni KE, Sah RK: Predictive value of symptoms for quality of life in firstepisode schizophrenia. Nordic Journal of Psychiatry 67(3):153–158, 2012. 10. Browne S, Roe M, Lane A, Gervin M, Morris M, Kinsella A, et al.: Quality of life in schizophrenia: Relationship to sociodemographic factors, symptomatology and tardive dyskinesia. Acta Psychiatrica Scandinavica 94(2):118–124, 1996 (Epub 1 Aug 1996). 11. Kemmler G, Meise U, Tasser A, Liensberger D, Schifferle I, Braitenberg M, et al.: Subjective quality of life of schizophrenic patients. Effect of treatment setting, psychopathology and extrapyramidal motor drug effects [Subjektive Lebensqualitat schizophren Erkrankter. Einfluss von Behandlungssetting, Psychopathologie und extrapyramidalmotorischen Medikamentennebenwirkungen]. Psychiatrische Praxis 26(1):9–15, 1999. 12. Loga-Zec S, Loga S: Antipsychotics and the quality of life of schizophrenic patients. Psychiatria Danubina 22(4):495–497, 2010 (Epub 21 Dec 2010). 13. Zouari L, Thabet JB, Elloumi Z, Elleuch M, Zouari N, Maalej M: Quality of life in patients with schizophrenia: A study of 100 cases [Qualite de vie des malades atteints de schizophrenie: etude de 100 cas]. L’Encephale 38(2):111–117, 2012 (Epub 21 April 2012). 14. Fujimaki K, Takahashi T, Morinobu S: Association of typical versus atypical antipsychotics with symptoms and quality of life in schizophrenia. PloS One 7(5):e37087, 2012. 15. Fang M, Li L, Zhao J, Chen H, Ye M, Guo X, et al.: Effect of antipsychotic drugs on life quality of schizophrenic patients: One year follow-up study. Zhong nan da xue xue bao Yi xue ban = Journal of Central South University Medical Sciences 34(9):850–855, 2009. 16. Chaves KM, Serrano-Blanco A, Ribeiro SB, Soares LA, Guerra GC, do Socorro Costa Feitosa Alves M, et al.: Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia. The Psychiatric Quarterly 84(1):125–135, 2013 (Epub 19 July 2012). 17. Cascade E, Kalali AH, Mehra S, Meyer JM: Real-world data on atypical antipsychotic medication side effects. Psychiatry (Edgmont) 7(7):9–12, 2010 (Epub 2 Sep 2010). 18. Rosa MA, Marcolin MA, Elkis H: Evaluation of the factors interfering with drug treatment compliance among Brazilian patients with schizophrenia. The Revista Brasileira de Psiquiatria 27(3):178–184, 2005 (Epub 15 Oct 2005). 19. Rocha FL, Hara C: Benefits of combining aripiprazole to clozapine: Three case reports. Progress in Neuro-psychopharmacology and Biological Psychiatry 30(6):1167–1169, 2006 (Epub 2 May 2006). 20. Viana Bde M, Prais HA, Camargos ST, Cardoso FE: Ziprasidone-related oculogyric crisis in an adult. Clinical Neurology and Neurosurgery 111(10):883–885, 2009 (Epub 1 Sep 2009). 21. American PA: Manual Diagno´stico e Estatı´stico de Transtornos Mentais—DSM-IV-TR-TM. Porto Alegre, ArtMed, 2003. 22. Human D: Declaration of Helsinki. Lancet 357(9251):236, 2001 (Epub 24 Feb 2001).
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Aurigena Antunes de Arau´jo is 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 Dantas is a student of the Post graduation program in Health and Society (UERN), Mossoro´, RN, Brazil. Gemma Galgani do Nascimento is a student of Nursing, UERN, Mossoro´, RN, Brazil. Susana Barbosa Ribeiro is 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 Silva is 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 Souza is a professor of Department public health and Post graduation program Public Health, UFRN, Natal, RN, Brazil. His research interests are public health and epidemiology.
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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.
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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
•
Ó Springer Science+Business Media New York 2014
Abstract This cross-sectional study compared the effects of treatment with atypical antipsychotic 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-economic 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 v2 test 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: [email protected] C. A. C. X. de Medeiros e-mail: [email protected] 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: [email protected] K. M. Chaves e-mail: [email protected] A. A. de Arau´jo D. L. B. de Souza Post Graduation Program Public Health, UFRN, Natal, RN, Brazil e-mail: [email protected] D. de Arau´jo Dantas Department of the Post Graduation Program in Health and Society/UERN, UERN, Natal, RN, Brazil e-mail: [email protected] G. G. do Nascimento Department of Nursing, UERN, Mossoro´, RN, Brazil e-mail: [email protected]
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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 ziprasidone 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 sociodemographic 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 medications 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 aripiprazole), 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: [email protected] 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: [email protected] C. A. C. X. de Medeiros Post Graduation Program in Health and Society (UERN), Mossoro´, RN, Brazil
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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 treatment; 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 healthrelated 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 secondgeneration 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: n¼
z2a=2 NPð1 PÞ e2 ðN 1Þ þ z2a=2 Pð1 PÞ
;
where n is the sample size, za/2 is 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
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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 v2 test 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. Significantly 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 salivation (quetiapine vs. ziprasidone, p = 0.03), orthostatic dizziness (risperidone vs. olanzapine, 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 medications 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,
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Psychiatr Q 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
Male (%)
73.7
52.8
43.5
57.7
69.2
0.031*
Female (%)
26.3
47.2
56.5
42.3
30.8
Sex
Years of education B8 (%)
91.9
95.8
91.3
80.8
100.0
[8 (%)
8.1
4.2
8.7
19.2
0.0
0.730
Employment Yes (%)
12.2
9.7
13.0
30.8
15.4
No (%)
87.8
90.3
87.0
69.2
84.6
0.114
Social security Yes (%)
62.7
52.8
60.9
50.0
69.2
No (%)
37.3
47.2
39.1
50.0
30.8
0.573
* 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
* Significant difference among groups
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
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Psychiatr Q 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
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
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
Neurological side effects
Autonomic side effects
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*
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
Other side effects
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Psychiatr Q 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
Group compared
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-generation 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 socioeconomic 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 Guidelines 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
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Fig. 1 Proportions of individuals reporting level 2/3 problems in EQ-5D dimensions, Natal, RN, Brazil, 2013
ziprasidone (memory difficulties and tension/restlessness) and clozapine (epileptic seizures) 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, especially 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.
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Aurigena Antunes de Arau´jo is 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 Dantas is a student of the Post graduation program in Health and Society (UERN), Mossoro´, RN, Brazil. Gemma Galgani do Nascimento is a student of Nursing, UERN, Mossoro´, RN, Brazil. Susana Barbosa Ribeiro is 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 Silva is 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 Souza is a professor of Department public health and Post graduation program Public Health, UFRN, Natal, RN, Brazil. His research interests are public health and epidemiology.
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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.
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