1 FACULTY OF MEDICINE, PSYCHIATRY DEPARTMENT,
KOLJA LEONARD TEN BRINK GEN. BERENTELG, MEDICINE INTEGRATED STUDIES
Master thesis 04/14/2021
PSYCHOTROPIC MEDICATION ADHERENCE AND ASSOCIATED FACTORS AMONG ADULT PATIENTS WITH SCHIZOPHRENIA
SUPERVISOR PROF. DR. V. ADOMAITIENE, CONSULTANT: ______________________
KAUNAS 2019-2021
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2. TABLE OF CONTENTS
3. SUMMARY ... 3
4. ACKNOWLEDGMENTS ... 4
5. CONFLICTS OF INTEREST ... 4
6. PERMISSION ISSUED BY THE ETHICS COMMITTEE ... 4
7. ABBREVIATIONS ... 5
8. TERMS ... 6
9. INTRODUCTION ... 7
10. AIM AND OBJECTIVES ... 8
11. LITERATURE REVIEW ... 9
12. RESEARCH METHODOLOGY AND METHODS ... 15
13. RESULTS ... 16
14. DISCUSSION OF THE RESULTS ... 24
15. CONCLUSIONS ... 28
16. PRACTICAL RECOMMENDATIONS ... 29
17. REFERENCES ... 30
18. ANNEXES ... 33
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3. SUMMARY
I, Kolja Leonard Ten Brink genannt Berentelg, author of this final master thesis have conducted research on the following topic: “Psychotropic medication adherence and associated factors among adult patients with schizophrenia”. The aim of this cross-sectional study is to assess treatment adherence and associated factors among adult schizophrenia ill patients in order to address risk factors of non-adherence and therefore be able to improve adherence and the prognosis of these patients. The objectives of this research are to identify sociodemographic and disease-related characteristics in schizophrenia ill patients, to determine treatment adherence and to identify and evaluate the differences between behaviour, attitude towards medications and side effects and attitude towards psychotropic medications in treatment adherent and non-adherent schizophrenia ill patients.
For this research’s purposes, 49 hospitalized adult schizophrenia patients of Kaunas clinics psychiatry department were queried, constituting a sample size of 49. The most adequate method to answer this thesis’ research question is written questionnaires. These were especially designed to acquire the following information: Sociodemographic patient data as well as medication adherence behaviour, attitude towards taking medication and negative side effects and attitudes towards psychotropic medication. Questions about age, gender, place of residence, education, employment status, age at the initial diagnosis of mental illness, number of hospitalisations due to mental disease, medication administration, and preference of medication administration, were also covered in the questionnaire. By using the Medication Adherence Rating Scale (MARS) the treatment adherence is evaluated in the previously described three dimensions (behaviour, attitude, side effects). It is asked, for example, if the patient has ever forgotten to take medication or if the patient is concerned about it. At the same time the questionnaire evaluates how the patient feels and if there is a correlation between adherence and the patient’s well-being. The main finding has been that urban area schizophrenia ill patients were significantly more adherent in their treatment process than rural area residents and that they had a significantly better attitude towards psychotropic medications. Further the mean age of male study participants in this sample at the time of data collection has been significantly higher than the mean age of female participants regarding a normal distribution. Regarding medication adherence it shows that the overall adherence rates are rather poor with a mean score of 5.27 (SD=2.008) with a range of 0–10.
We found that 83.7% of all schizophrenia ill patients (n=41 vs 8) regardless of the sex did not adhere to their treatment. Hereafter, research should focus on targeted, profound, longitudinal studies in order to improve treatment outcomes and prognosis of the patients. Future treatment approaches should be more targeted and patient-focused, as it has been observed in previous literature that the risk factors of medication non-adherence can be various.
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4. ACKNOWLEDGMENTS
I would like to thank my supervisor professor Adomaitienė for her help and advice during the process of writing this final master thesis. Furthermore, I would like to thank LSMU resident doctor __________ for his support in finalizing this thesis by obtaining patient data during the periods of quarantine. Further, I would like to thank the LSMU statistics department for the statistical analysis of our research results.
Last but not least, I would like to thank my parents for their overwhelming support during the last six years.
5. CONFLICTS OF INTEREST
The author reports no conflicts of interest.
6. PERMISSION ISSUED BY THE ETHICS COMMITTEE
The Bioethics centre of the Lithuanian University of Health sciences approved the student's research work on the topic “Psychotropic medication adherence and associated factors among adult patients with schizophrenia” Nr. BEC-MF-146 on the 12.13.2019 after evaluating the documents submitted by the student Kolja Leonard Ten Brink Genannt Berentelg.
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7. ABBREVIATIONS
Abbreviation Definition
(MARS) Medication Adherence Rating Scale
(BARS) Brief Adherence Rating Scale
(KMARS) Korean version of Medication Adherence Rating
Scale
(CATIE) Clinical Antipsychotic Trials of Intervention
Effectiveness
(EUFEST) European First Episode Schizophrenia Trial
(TR) Therapeutic relationship
(LAI) long-acting injectable
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8. TERMS
Term Description
Adherence i.e. the extent to which an individual follows prescribed drug regimens and medical advice.
Insight is an individual's awareness and understanding of their current medical problem.
long-acting injectable formulations intended for prolonged/sustained drug release over a long period of time
Risk factor a variable or attribute that increases the probability of developing a disease or injury
Schizophrenia Schizophrenia is a severe psychiatric disorder characterized by chronic or recurrent psychosis.
Therapeutic relationship the relationship through which a patient and clinician engage with one another to work toward a therapeutic goal for the patient.
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9. INTRODUCTION
Schizophrenia is one of the most severe psychiatric disorders and often associated with a poor prognosis. One of the reasons for a poor prognosis is that patients do not take their medication with antipsychotic medication being the primary treatment. Therefore, one of the biggest challenges in treating patients diagnosed with schizophrenia is treatment adherence. Non-adherence to medication is a major problem in medicine, especially for chronic illnesses, as adherence rates are even lower in these conditions. Non-adherence to therapy is associated with poorer treatment outcomes. Higher rates of relapse and rehospitalisation, worsening of signs and symptoms, poorer mental functioning, lower life satisfaction, higher substance use, increased hospital costs, violence, arrests and victimisation are observed [1] [2]. According to Gilmer et al. mean rates of medication adherence in Schizophrenia patients are reported to be 41% [3].
As mean adherence rates are reported to be low it is critical to address risk factors of medication non- adherence in order to be able to improve adherence rates, treatment outcomes and hence prognosis of schizophrenia patients.
By means of questionnaires, sociodemographic patient data such as age, sex, place of residence, education, employment status, age at initial diagnosis of mental illness, number of hospitalisations due to mental disease and medication administration are collected to determine risk factors of treatment adherence. Furthermore, the aim of this cross-sectional study is to assess psychotropic medication adherence rates among the study participants using Medication Adherence Rating Scale (MARS) by asking the patients about medication adherence behaviour, attitude towards taking medication and negative side effects and attitudes towards psychotropic medication. In short, this research aims to assess treatment adherence and associated factors among adult schizophrenia ill patients.
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10. AIM AND OBJECTIVES
Aim:
The aim of this cross-sectional study is to assess treatment adherence and associated factors among adult schizophrenia ill patients.
Objectives:
1. To identify sociodemographic and disease-related characteristics in schizophrenia ill patients.
2. To determine treatment adherence in schizophrenia ill patients.
3. To identify and evaluate the differences between behaviour, attitude towards medication and side effects and attitude towards psychotropic medications in treatment adherent and non-adherent schizophrenia ill patients.
4. To identify the impact of sociodemographic characteristics on behaviour, attitude towards medication and side effects and attitude towards psychotropic medications in schizophrenia ill patients.
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11. LITERATURE REVIEW
Adherence has been defined as „the extent to which a patient's behaviour coincides with medical or prescribed health advice” [4]. It describes the adherence of the therapy goals jointly set by patient and practitioner within the framework of the treatment process. In the past, the term “compliance” was used more frequently, but it only focuses on the patient's unilateral adherence to the therapy. It ignores the fact that the cooperation of both treatment partners (patient and doctor) is necessary for a successful therapy. Poor treatment adherence may include, for example, to refuse to attempt medical appointments or to start a treatment program, the partial implementation of medical advice given or the early treatment discontinuation [5].
Mean rates of medication adherence in Schizophrenia patients are reported to be 41% according to Gilmer et al. [3]. Lacro et al. report of non-adherence rates of 41.2% among schizophrenia patients [6].
Mean rates of adherence vary strongly among different studies which is most likely due to inconsistent methodologies of how to access medication adherence [6] [7].
There are objective / direct methods and subjective / indirect methods to access medication adherence.
Objective methods are, for example, observing the patient while swallowing tablets, measuring of blood or urine parameters, electronic medication monitors and pill counts. Patient self-reporting and Brief Adherence Rating Scale (BARS), Medication Adherence Rating Scale (MARS), among many others, belong to the subjective / indirect methods, which are more popular and most commonly used in approximately 75% of the cases [8]. There are no uniform criteria defining the lack of adherence [6].
Also, up to this point there is no clear definition of what defines adherence in terms of degree of adherence. Sendt et al. report numbers defined as adherence ranging from 47.2% to 95% among the studies included in their systematic review [7]. According to literature, different classifications of adherence have been described. There are dichotomous and trichotomous approaches differentiating between adherence and non-adherence and good, moderate and poor adherence, or full-, partial- and non-adherence respectively [7]. Often, good adherence is defined as the consumption of ≥ 75% of the medication provided [9] [10].
Reviewing cross-sectional studies, cohort studies, follow-up studies, meta-analysis, systematic reviews and comprehensive reviews, the following factors were described as the main risk factors for medication nonadherence in schizophrenia patients. Poor insight [7,9,11–14], poor neurocognitive functioning [9,11,15], negative attitude [7,16], previous non-adherence [6], worse therapeutic relationship [7,10,12,16], hostility [14], substance abuse and alcohol [9,14], side effects of antipsychotic medication [9,16], length of hospital stay [17], and lack of family support [16].
10 In the following, rates of medication adherence and risk factors of medication non-adherence will be discussed and divided into the following categories: patient related factors, drug treatment related factors, and factors associated with social relationships.
Medication adherence:
Jónsdóttir et al. accessed medication adherence among schizophrenia patients by objective and subjective measures as serum concentrations and self-report using a Likert scale (0% -100%). Further, they grouped the participants of the cross-sectional study into “full, partial, no” adherence. Patients who reported 100% adherence, and where the serum concentration was within reference level and in correct ratio with the dose, were defined as full adherent. Patients who reported 0% adherence and / or the serum concentration showed no detectable drugs were assigned to the no-adherence group. The remaining participants reporting of adherence between 12% - 95% or the concentration ⁄ dose ratio was lower than the reference values, but with detectable medication in serum, were assigned to the partial-adherence group. The full-adherence group involved 55% of the schizophrenia patients, the partial-adherence group 34% and the non-adherence group 11% [9] [5]. A cross-sectional study by Na et al. found results of medication adherence related to Jónsdóttir et al. reporting of generally high adherence rates as nearly 85% using the Korean version of Medication Adherence Rating Scale (KMARS) and only 15% of poor adherence among chronic schizophrenia patients [11]. A score of less than six has been considered as poor adherence. The good adherence rates were possibly obtained due to the inclusion criteria of the study. Only patients with a disease duration of over 10 years were enrolled. Yet, Lacro et al. reported 58.8% adherence using strict criteria and of 49.5% adherence using stricter criteria. Strict criteria have been described as regularly taking medications as prescribed. Stricter criteria have been described as taking medications as prescribed at least 75% of the time. Method of assessment has been a subjective, a Likert-type assessment scale [6]. Baloush-Kleinman et al. used as a subjective method the Visual Analogue Scale for Assessing Treatment Adherence (VAS-ATA) (0 - 100%), which was rated by study participants, relatives and treating physicians. The mean adherence rate reported has been 70.2% [7,16].
McCabe et al. categorized the participants in a trichotomous model into good ≥75%, average = 25–75% and poor ≤25% adherence and used subjective, clinician rated Buchanan criteria, reporting of 72.4% mean adherence rates. In the majority of cases collateral information was also used [7,10]. El-Missiry et al. reported that only one third (31.2%) of the patients were adherent to their medication and nearly two thirds (68.8%) of their patients were not. They assessed the patients adherence by the Brief Adherence Rating Scale (BARS) a subjective method [15]. Novick et al. assessed medication adherence using MARS and reports of a mean score of 5.8 (on a 10 point scale) (p <0.001) which indicates that some of the participants were adherent to their treatment and some were not. A score of < 6 is considered as a poor level of adherence [12].
11 Patient related factors
Those include attitudes and behaviours, comorbidities and the severity of signs and symptoms, demographic and environmental factors, cognitive functioning of patients and their relationship with their medication [5].
In a cross-sectional study Jónsdóttir et al. analysed 154 Schizophrenia patients by clinical assessments, neurocognitive testing and blood sampling and found an association between poor adherence and reduced insight and poor adherence and the use of illicit substances and alcohol [9]. The correlation between insight and adherence is consistent in the literature and supported by an observational study by Novick et al. who found that better insight was closely related to better adherence. They included 612 Schizophrenia patients in a 1-year outpatient observational study conducted in Europe [12]. These findings are consistent with those of Baloush-Kleinman et al. [16]. Na et al. also found that patients with good insight were more likely to maintain their medication (p=0.0005) [11]. Besides substance use (p=0.0003) and poor insight (p≤0.0001) Czobor et al. also found that worse medication adherence was correlated with higher levels of hostility (p=0.0002) [14]. This finding is in agreement with those of Lindenmayer et al. who showed in a post hoc analysis that increased hostility was a significant risk factor for treatment non-adherence [18]. An interesting finding in the study of Jónsdóttir et al. was that patients of the partial adherence group more often used illicit drugs and alcohol compared to the full- and non- adherence group. Furthermore, they were more often diagnosed being addicts [9]. It could be expected that with decreasing adherence the use of illicit substances and alcohol increases. Or vice versa, with increasing intake of alcohol and illicit substances it would be expected that adherences decreases. It turned out that the partial adherence group was most affected by the use of illicit substances and alcohol, not the non-adherence group. Furthermore, Czobor et al. observed that worse adherence leads to earlier treatment discontinuation. But in case of drug abuse, it remains unclear whether substance use precedes non-adherence or vice versa. Czobor et al. combined the data from Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and The European First Episode Schizophrenia Trial (EUFEST) and thereby analysed a total of 1154 schizophrenia patients [14]. A longitudinal study conducted by Barbeito et al. confirmed high rates of cannabis use among patients hospitalized with first-episode psychosis. They furthermore analysed factors of treatment adherence such as involuntary first admission and stopping cannabis use [19]. Among their study participants 57.1% had an involuntary first admission, 74.4% were poorly adherend and 52% used cannabis. Changes in the adherence pattern included that 43.4% of the patients were always bad, 25% were always good and 25% improved from bad to good. Using logistic regression models the researchers identified better long-term adherence among patients who never used cannabis or who stopped using it. Furthermore they found that adherence
12 during follow-up was also better in patients with involuntary first admission [19]. Jónsdóttir et al. made another interesting observation, patients of the poor adherence group in their study performed better on neurocognitive tests, measuring verbal learning capacity, memory and higher IQ, compared to patients from a better adherence group (partial or full adherence) [9]. These findings conflict with those obtained by El-Missiry et al. who found that the adherent patients of their study scored better on cognitive and executive function tests reflecting the higher IQ’s of the patients. The researchers concluded that
“cognitive deficits, especially verbal memory and executive functions were the strongest patients' related factors associated with non-adherence to medication“ [15]. El-Missiry et al. conducted a prospective cohort study among adult patients diagnosed with Schizophrenia in order to answer the question if cognitive dysfunction does relate to psychotropic medication non-adherence. Using Brief Adherence Rating Scale (BARS) they assessed the adherence rates among their patients six months after initial assessment of cognitive and executive functions between adherent and non-adherent patients using Wechsler Adult Intelligence Scale (WAIS), Wechsler Memory Scale-Revised (WMS-R) and Wisconsin Card Sorting Test (WCST). Those tests apply to be the Gold standard evaluating Cognitive functions which encompass domains like executive functions as memory, attention, vigilance, verbal tasks and social cognition [15]. The study by Na et al. confirmed the results obtained by El-Missiry et al. they also found that better executive function was associated with increased medication adherence (p = 0.0008).
They analysed 104 schizophrenia patients in a Korean cross-sectional study. Furthermore they found that fewer depressive symptoms were associated with good medication adherence (p = 0.0304) [11].
Analysing schizophrenia patients Baloush-Kleinman et al. showed by the usage of statistical means that adherence was predicted by factors as symptom severity, awareness for the need of medication and the attitude towards medication. The following four aspects awareness of the need for medication, awareness of social consequences, patient’s perceived confidence in the treating doctor, and the severity of negative symptoms predicted attitudes towards medication, which in turn predicted adherence.
Summarizing Baloush-Kleinman et al. found that more positive attitudes to medication were linked to better adherence [16]. On the other hand, Jónsdóttir et al. could not prove that severity of symptoms is a risk factor for nonadherence [9].
Analysing schizophrenia patients Bodén et al. could not find a significant association among demographic risk factors as sex, age, place of birth and urban area residence in a population-based cohort study [17]. This is in line with the findings of Bitter et al. who could not find a significant relationship between adherence and demographic and environmental risk factors as age, gender and years of education in their cross-sectional study [13]. Further Baloush-Kleinman et al. could not find significant differences between adherent and non-adherent patients related to demographic and environmental factors as sex, education, marital status, employment status, ethnicity [16]. Sendt et al. reported conflicting results regarding demographic and environmental factors. Conducting a systematic review
13 they analyized more than 5000 mainly adult schizophrenia patients and obtained results from 13 observational studies [7]. The authors reported that only a few studies found significant positive associations between demographic and environmental factors and adherence, in particular married status, higher education, being employed and female gender. Worth mentioning is that those studies comprise only small sample sizes ranging from 50 – 100 patients [7,20,21]. These findings are supported by Abdel-Baki et al. who found that a better disease outcome was predicted by being married and female;
furthermore by older age at admission and higher premorbid autonomy in living arrangements [22].
Drug treatment related factors
Those include length of hospital stay, first - versus second- generation antipsychotic drugs, and side effects of antipsychotic medication.
A population-based cohort study by Bodén et al. looked at non-adherence and its risk factors from a different perspective. By using Swedish national health and population registers they tried to access risk factors for rehospitalization in recent onset Schizophrenia patients of adult age. They found two potentially modifiable risk factors. The authors claimed that a first hospitalization of short duration after recent onset Schizophrenia increases the risk of rehospitalization and early non-adherence. Bodén R. et al. defined early non-adherence as “not having filled a prescription of antipsychotic medication within the first week after discharge from the index hospitalization” [17]. Analysing their findings one may find an association between risk factors of rehospitalization and risk factors of non-adherence to medication. Short duration of initial hospitalization increases the risk of non-adherence. This may be due to the circumstances that a patient who is released early from the hospital did not have enough time to experience positive effects of the medication and might still be psychotic and with poor insight [17].
There is a direct correlation between early hospital discharge and non-adherence to medication. During longer hospitalization routines for daily medications, family involvement and discharge planning can be achieved [17]. Also its more likely to establish a good therapeutic alliance which subsequently helps the patients to adhere to their treatment as Reutfors et al. reports [23]. Thus, a longer hospital stay favours medication adherence. Further Tiihonen et al. observed that the risk of rehospitalization is also related to the application form of antipsychotics. They found that patients receiving medication by depot administration had a significantly lower risk of rehospitalization compared to oral formulations of the same compounds [24]. In addition to that Zhou et al. analysed factors being associated with complete discontinuation of medication being a major risk factor for relapse in schizophrenia and found that about 25% of the participants being included into the study discontinued their medication therapy within one year after discharge from that hospital. Using Logistic regression analysis they found that shorter duration of illness, meaning patients who were diagnosed with schizophrenia recently, lack of health
14 insurance, and poor insight at the time of discharge were significantly associated with complete discontinuation of medication (p<0.05) [25].
Caseira et al., however, conducted a three-year follow-up study in order to find out which factors predict a relapse after a first episode of non-affective psychosis and reports that only medication adherence has shown to be a significant predictor of relapse after a three-year follow-up [1].
Looking into side effects of antipsychotic medication in previous literature it has been expected that extrapyramidal symptoms would be associated with non-adherence. In the metanalysis carried out by Czobor et al., a significant correlation between side effects of antipsychotic treatment as akathisia and dyskinesia (extrapyramidal symptoms) and adherence rates could not be found. Patients experiencing akathisia and or dyskinesia did not show significantly worse adherence to medication [14]. Jónsdóttir et al. only found a significant association between some autonomic side effects as diarrhea, nausea and orthostatic hypotension and worse adherence [9]. Neither Jónsdóttir et al. nor Baloush-Kleinman et al.
could find a significant association between worse adherence rates and extrapyramidal symptoms.
Baloush-Kleinman et al. also analysed drug treatment related factors as treatment side effects in particular extrapyramidal symptoms and first - versus second- generation antipsychotic drugs. Neither for adverse effects, nor for the type of antipsychotics (FGAs/SGAs) they could find a significant association [16]. This suggests that findings among side effects regarding the question of parkinsonism being a risk factor for non-adherence are consistent in the literature.
Factors associated with social relationships
Those include therapeutic alliance, and family support.
McCabe et al. found an association between therapeutic relationship (TR) and adherence to medication.
They investigated if TR is associated with antipsychotic medication adherence in adult schizophrenia patients by examining both the patients and doctors ratings of the TR. They made an interesting finding, the TR rated by the patient and doctor only weakly intercorrelated. But at the same time each was linked with better adhearance. They concluded that both the patients and doctors view on the TR is important, although they might reflext different aspects [10]. McCabe et al.’s study showed that a better therapeutic alliance increases adherence. This may be due to the assumption that a better TR predicts a better attitude towards medication and therefore increases adherence rates [10]. In the literature poor therapeutic alliance has been described as a risk factor to medication adherence, hence Novick et al. reports of better medication adherence correlated with a better therapeutic relationship and furthermore findings as an association between better TR and better overall functioning and milder clinical severity of mental illness [12]. Novick et al. emphasized that therapeutic alliance, insight and treatment adherence are strongly
15 correlated with each other and that an improvement in one of the mentioned factors would be accompanied by improvements of the others. These findings are in line with previous literature [26].
Also, Baloush-Kleinman et al. found that patients of good medication adherence were associated with significantly more positive perceptions of trust in the therapeutic relationship and furthermore with significantly more perceived family involvement in pharmacological treatment and positive attitudes towards medication in the family [16].
12. RESEARCH METHODOLOGY AND METHODS
Methodology:
49 Hospitalized adult schizophrenia patients of Kaunas clinics psychiatry department were asked to take part in the research by filling written questionnaires. Inclusion criteria of the study were a diagnosis of schizophrenia and adult age of the patients. The method of research are questionnaires in Lithuanian and English language obtaining sociodemographic patient data as well as medication adherence behaviour, attitude towards taking medication and negative side effects and attitudes to psychotropic medication. Questions about age, gender, place of residence, education, employment status, age when mental illness was diagnosed first, number of hospitalisations due to mental disease, mediation administration, and preference of medication administration, were also covered in the questionnaire (Annex 1, Annex 3). By using the Medication Adherence Rating Scale (MARS) (Annex 2, Annex 4) invented by Thompson et al. [27] the treatment adherence is evaluated in the previously described three dimensions (behaviour, attitude, side effects). It was asked, for example, if the patient have ever forgotten to take medication, or if the patient is concerned about it. And at the same time the questionnaire evaluates how the patient feels and if there is a correlation between adherence and the patient’s well-being. The MARS questionnaire is a 10-item self-reported measure ranging from 0 to 10 with a high score being associated with better adherence. Participants should be asked to respond to the statements in the questionnaire by marking the answer which best describes their behaviour or attitude towards their medication during the past week. Each question is weighted one point. A score of less than six points is associated with poor adherence according to Na et al. [11].
Following the data collection, we used Microsoft Excel for further analysis. Statistical methods as tests of normality such as the Kolmogorov–Smirnov test and the Shapiro–Wilk test were performed. Further Test statistic using Mann–Whitney U test and statistical hypothesis test as the Chi-squared test were performed. Statistically significant p value was at 0.05.
16 The statistical analysis was initiated by my supervisor professor Adomaitienė and performed by the LSMU statistics department.
Search strategy:
To find appropriate literature a systematic search was performed using PubMed data base. All articles were included starting from the year 2011. The search strategy included the following Medical subject headings (MeSH - terms): „Psychotropic medication adherence and associated factors among adult patients with schizophrenia [MeSH Terms].” The following filters were used: Abstract, Humans, English, Adult: 19+ years, from 2011 – 2020 Results: 91. Key references from relevant articles were searched for additional material.
Inclusion and exclusion criteria:
All study types were included in the search. Limits applying to the search were articles not written in English, articles to which only the abstracts were publicly published and duplicates. The titles and abstracts of all identified citations were evaluated for eligibility. All eligible articles were analysed in full text. Studies were excluded if not matching the inclusion criteria or were not in alignment with this master thesis objectives.
13. RESULTS
13.1. Sociodemographic characteristics of schizophrenia ill patients
In total, 49 patients were included in the study. The mean age of all participants was 36.69 years (SD = 15.41). Male participants in this sample were significantly older with an average of 39.55 (SD = 15.81) years regarding a normal distribution and also had a greater age range ranging from 18 -74 years.
Women on the other hand were significantly younger, with an average of 34.72 (SD = 15.08) years and the age range was smaller, ranging from 20 - 67 years (Table 1). Previous statistical analysis showed
17 using the Kolmogorov-Smirnov-Test a test of normality, that we had to reject the null hypothesis (p>0.05) and accept the alternative hypothesis (p≤0.05). Regarding the sample distribution this means that our study participants in regard to their age are not sampled from a population that follows a normal distribution.
Table 1. Sociodemographic characteristics of schizophrenia ill patients
Characteristics, variable All (n=49)
Male (n=20)
Female (n=29)
p Age, mean (SD),
years range
36.69 (15.41) 18-74
39.55 (15.81) 18-74
34.72 (15.08) 20-67
0.002
Gender, M/F, n (%)
20/29 (40.8/59.2)
- - ns
Residential area, rural/urban, n (%)
15/34 (30.6/69.4)
- - ns
Education,
<12/≥12, n (%)
18/31 (36.7/63.3)
- - ns
Employment status, employed/unemployed/student,
n (%)
15/29/5 (30.6/59.2/10.2)
- - ns
Age at first diagnosis, mean (SD)
23.20 (9.04) - - ns
Inpatient status, mean (SD)
8.37 (8.43) - - ns
Form of medication used, tablets/injections/LAI
n (%)
47/1/1 (96.0/2.0/2.0)
- - ns
Preference of medication, tablets/LAI/not important, n (%)
37/6/6 (75.6/12.2/12.2)
- - ns
Sch, schizophrenia; p, value between two groups; ns, not significant; significant p-value (p<0.05); M, male; F, female; SD, standard deviation; LAI, long acting injections.
18 The gender distribution in our sample was 40.8% (20/49) male participants and 59.2% (29/49) female participants. The significance value was found to be not significant.
Fig. 1 Gender distribution among study participants.
Two thirds of the patients lived in urban areas and only one third in rural areas: 69.4 % (34/49) vs 30.6%
(15/49).
Fig. 2 Place of residence of study participants.
19 Looking into the educational background of the participants we found that 63.3 % (31/49) of the patients had ≥ 12 years of education while only 36.7 % (18/49) had < 12 years of education.
Fig. 3 Years of education.
We found that 30.6% (15/49) of the patients were working before being hospitalised, 10.2% (5/49) were students and 59.2% (29/49) stated that they were unemployed.
Fig. 4 Employment status.
20 The mean age at the initial diagnosis of schizophrenia was 23.20 years (SD = 9.04) while 95% of the participants were 20 – 25 years old (95% CI 20.61 – 25.80). The median has been 20 years of age, while the age at the initial diagnosis ranged from 7 – 45 years.
We found that our patients were hospitalised 8.37 (SD = 8.43) times on average since the initial diagnosis While the vast majority were hospitalized ranging from approximately 6 - 11 times 95% CI (5.94 – 10.79). The median has been 5 hospitalizations while the minimum of hospitalizations was 1 and the maximum count 40 times.
Asking the participants on which way they received their medication 95.9 % (47/49) stated to swallow tablets, while only 2% (1/49) received their medication by injections and another 2% (1/49) as long- acting injectable (LAI) formulations.
Fig. 5 Form of medication used.
Questioning the patients about their preferences in medication formulation 75.6% (37/49) preferred tablets, while the remaining 24.4% (12/49) split in half stating that they would prefer injections or long- acting injectable (LAI) formulations.
21 Fig. 6 Preference of medication
13.2. Demographic and illness related characteristics of adherent and non-adherent patients
Analysing the overall results from the MARS questionnaire we found that 83.7% of all schizophrenia ill patients (n=41 vs 8) regardless of gender (male - 85.0% vs 15.0% and female - 82.7% vs 17.2%) did not adhere to their treatment. The mean MARS score for the 49 participants was 5.27 (SD = 2.008), with a range of 0–10. The median score was 5.00, with an interquartile range of 4.00 to 7.00. There was no evidence of a difference in MARS total score between gender (p=0.918), the mean score for male was 5.20 (SD = 2.042) with median score 5.50 (interquartile range 3.50-6.00) and for female the mean score was 5.31 (SD = 2.020) with median score 5.00 (interquartile range 4.00-7.00). Both, adherence and non- adherence did not depend on gender: 37.5% (3/20) of male and 62.5% of female (5/29) were adherent, 41.5% (17/20) of male and 58.5% (24/29) were non-adherent in their treatment process (p > 0.05; Table 2). The mean age of the adherent and non-adherent schizophrenia ill patients was not significantly different: the mean age of non-adherent was 35.90 (SD = 15.440) years, and the mean age of adherent subjects was 40.75 (SD = 15.618) years (p > 0.05). It was found that urban area residents with schizophrenia were significantly more adherent in their treatment process than rural area residents (p=0.004). Both, adherence and non-adherence did not depend on schizophrenia ill patient’s education in years, employment status, age at first diagnosis of schizophrenia, inpatient status, form of medication used and preference of medication (p > 0.05). No significant differences were found between treatment adherent and treatment non-adherent patients depending on employment status (employed - 12.45% vs.
34.2%, unemployed - 62.5% vs. 58.5% and students - 25.0% vs. 7.3%; p > 0.05). Non-adherent subjects were first diagnosed with schizophrenia at a mean age of 22.85 (SD = 9.205) years (median score 19.00,
22 with an interquartile range of 18 to 24), and adherent at mean age of 25.00 (SD = 8.519) years (median score 22.50, with an interquartile range of 20.50 to 25.50). These two groups did not differ significantly between each other (p > 0.05). Non-adherent subjects in psychiatric hospitals were treated on average 8.85 (SD = 8.960) times (median score 5.0, with an interquartile range of 3 to 10) and adherent subjects were treated 5.88 (SD = 4.549) times (median score 4.5, with an interquartile range of 2 to 10). These two groups did not differ significantly between each other (p > 0.05). It was found that 100% adherent and 95.2% non-adherent patients were treated with treatment processes using tablet formulations of psychoactive medications (p > 0.05).
Table 2 Sociodemographic and illness related characteristics of adherent and non- adherent patients
Characteristics Variability Adherent (n; %)
Non-adherent (n; %)
p
Gender Male
Female
3 (37.5) 5 (62.5)
17 (41.5) 24 (58.5)
ns Age (years) Mean (SD) 40.75 (15.618) 35.90 (15.440) ns Residential area Urban
Rural
8 (100.0) 0 (0)
26 (63.4) 15 (36.6)
0.04 Education in years <12
≥12
1 (12.5) 7 (87.5)
17 (41.5) 24 (58.5)
ns Employment status
n (%)
Employed Unemployed
Student
1 (12.5) 5 (62.5) 2 (25.0)
14 (34.2) 24 (58.5) 3 (7.3)
ns
Age at first diagnosis mean (SD) 25.00 (8.519) 22.85 (9.205) ns Inpatient status mean (SD) 5.88 (4.549) 8.85 (8.960) ns Form of medication used Tablets
Injections LAI
8 (100) 0 0
39 (95.2) 1 (2.4) 1 (2.4)
ns
Preference of medication Tablets LAI Not important
6 (75.0) 0 2 (25.0)
31 (75.6) 6 (14.6)
4 (9.8)
ns
p, value between two groups; ns, not significant; significant p-value (p<0.05); M, male; F, female; SD, standard deviation; LAI, long acting injections. MARS score ≤7 - Non-adherent; MARS score >7 – Adherent.
23 13.3. Treatment regime (behaviour), attitude towards medication and side effects and attitude to psychotropic medication in treatment adherent and non-adherent schizophrenia ill patients.
Significantly higher mean MARS scores were found in the treatment adherent group in all subscales:
behaviour (3.62 (SD = 0.744) vs 2.31 (SD = 1.082); p=0.002), attitude towards medication and side effects (2.75 (SD = 0.707) vs 1.75(SD = 0.888); p=0.007) and attitude to psychotropic medication (1.87 (SD = 0.353) vs 0.60 (SD = 0.737); p=0.0001). (Table 3).
Table 3 Behaviour, attitude towards medication and side effects and attitude towards psychotropic medication between treatment adherent and non-adherent schizophrenia ill patients
Characteristics Adherent
(mean SD)
Non-adherent (mean SD)
p
Behaviour 3,62 (0,744) 2,31 (1,082) 0.002
Attitude towards medication and side
effects
2.75 (0.707) 1.75 (0.888) 0.007
Attitude towards psychotropic medication
1.87(0.353) 0.60 (0.737) 0.0001
p, value between two groups; significant p-value (p<0.05); SD, standard deviation; MARS score ≤7 - Non-adherent; MARS score >7 – Adherent.
13.4. Behaviour, attitude towards medication and side effects and attitude towards psychotropic medications and sociodemographic characteristics of schizophrenia ill patients.
No significant differences were found in behaviour, attitudes towards medication and side effects, and attitudes towards psychotropic medication according to gender, age, years of education, employment status, age at initial diagnosis of schizophrenia, inpatient status, form of medication used, and medication preference (p>0.05) (Table 4). However, we found that patients with schizophrenia living in urban areas had more positive attitudes towards psychotropic medication (1.08 (SD 0.792) vs 0.20 (SD 0.560);
p=0.001).
Table 4 Behaviour, attitude towards medication and side effects and attitude towards psychotropic medications and sociodemographic characteristics of schizophrenia ill patients.
24 Characteristics Variability Behaviour
(mean SD)
Attitude towards medication and
side effects (mean SD)
Attitude towards psychotropics
(mean SD)
p
Gender Male
Female
2.35 (1.367) 2.65 (1.142)
2.05 (1.099) 1.82 (0.804)
0.80 (0.894) 0.82 (0.804)
ns
Age (years) Mean (SD) - - - ns
Residential area
Urban Rural
2.70 (1,115) 2.13 (1,125)
2.02 (0,869) 1.66 (1,046)
1.08 (0.792) 0.20 (0.560)
0.001 Education in
years
<12
≥12
2.72 (1,227) 2.41 (1,082)
1.77 (0.942) 2.00 (0.930)
0.72 (0.751) 0.87 (0.884)
ns Employment
status
Employed Unemployed
Student
2.33 (0.975) 2.65 (0.142) 2.40 (0.673)
1.80 (0.861) 1.96 (0.051) 2.00 (0.000)
0.86 (0.833) 0.79 (0.818) 0.80 (0.095)
ns
Age at first diagnosis
< 20
≥ 20
2.31 (0.945) 2.70 (0.265)
1.95 (0.045) 1.88 (0.847)
0.68 (0.893) 0.92 (0.780)
ns Inpatient
status
≤ 5
> 5
2.37 (1.082) 2.75 (1.208)
1.89 (0.939) 1.95 (0.944)
0.75 (0.830) 0.90 (0.852)
ns Form of
medication used
Tablets Injections/
LAI
2.55 (0.157) 2.00 (0.000)
1.89 (0.937) 2.50 (0.707)
0.78 (0.832) 1.50 (0.707)
ns
Preference of medication
Tablets LAI
2.62 (0.036) 2.25 (0.422)
1.86 (0.004) 2.08 (0.668)
0.81 (0.844) 0.83 (0.834)
ns Age at first diagnosis median (< 20 vs ≥ 20) in years; Inpatient status (≤ 5 vs > 5) median; ns (p > 0.05);
LAI, long acting injectable psychotropic medications. SD, study deviation.
14. DISCUSSION OF THE RESULTS
In the present study, we used questionnaires to obtain a reliable measure of adherence among our study participants and to identify sociodemographic and disease-related characteristics in schizophrenia ill patients. The main finding has been that urban area schizophrenia ill patients were significantly more adherent in their treatment process than rural area residents and that they had a significantly better attitude towards psychotropic medications.
In our research, object of the study were hospitalised schizophrenia patients who were on average 36.69 years old (SD = 15.41) at the time of data collection and who were diagnosed with schizophrenia for the first time with a mean age of 23.20 years (SD = 9.04). Further they had 8.37 (SD = 8.43) previous hospital admissions in the past. With regard to the discussion of results it means we are analysing
25 schizophrenia patients with a known diagnosis of schizophrenia for 13.49 years on average and that the number of first episode schizophrenia patients among our study sample is very low knowing that the vast majority was hospitalized approximately 6 - 11 times 95% CI (5.94 – 10.79). Keeping those characteristics in mind a comparison of results with previous research among chronic schizophrenia patients is reasonable.
In our sample we found that the overall adherence rates were rather poor with a score of 5.27 (SD = 2.008) points on average. After grouping the patients into adherent and non-adherent, we found that 83.7% of all schizophrenia ill patients (n=41 vs 8) regardless of the gender (male - 85.0% vs 15.0% and female - 82.7% vs 17.2%) did not adhere to their treatment. They scored ≤7 points on MARS which may be considered non-adherent. The group of adherent patients was small, comprising 16.3% of all schizophrenia ill patients (n=8 vs 41) scoring >7 points on MARS which may be considered adherent.
Our results are in line with previous literature by Novick et al. who reports of a mean score of 5.8 (SD
= 2.7) (p < 0.001) on MARS among study participants [12]. Using BARS El-Missiry et al. reports of low adherence rates, 31.2% adherence and 68.8% non-adherence respectively among study participants [15]. A cross-sectional study by Na et al. presented results of medication adherence reporting generally high adherence rates as nearly 85% using the Korean version of Medication Adherence Rating Scale (KMARS) and only 15% of poor adherence among chronic schizophrenia patients [11]. As previously mentioned, mean rates of adherence vary strongly among different studies which is most likely due to an inconsistent methodology of how to access medication adherence [6] [7]. For better comparability, I compared my results with other studies using the same methodology in assessing adherence (MARS and BARS). Both belong to the subjective / indirect methods to access medication adherence and rates were analysed in a dichotomous approach differentiating between good adherence and poor adherence.
Nevertheless, we found adherence rates varying from 31% - 85% among different studies. This means that not only the uniform methodology must be taken into account, but even more so the comparability of study participants in regard to stage of disease. High adherence rates are more likely among chronic schizophrenia patients, due to better insight, being less psychotic and having established a better TR over time. Thus, Na et al. found high rates of adherence among study participants, as they had a known diagnosis of schizophrenia for about 30 years [11]. Yet, El-Missiry et al. reported low adherence rates of 31% with a mean age of 32 years (SD = 8.6) among study participants, which obviously indicates a shorter disease duration considering epidemiological data showing that the typical age of onset is in the late teens to mid-thirties [28] [29].
Among demographic factors we found that our hospitalized schizophrenia patients had statistically significant age differences between the sexes, male study participants in this sample being significantly older at the time of data collection compared to female participants regarding a normal distribution. The age difference was approximately five years on average. (Male average age of 39.55 (SD = 15.81) and
26 women 34.72 (SD = 15.08)) Furthermore male patients also represented the youngest and oldest participants in the study showing a greater age range ranging from 18 -74 years. The mean age of all participants was 36.69 years, (SD = 15.41). The latest finding is in line with previous literature Jónsdóttir et al reports of age, mean (SD) 33.2 (9.3) among schizophrenia patients (N = 154). Study participants were referred to the study from outpatient clinics which [9]. In the CATIE study (N=851) Czobor et al.
reports of mean age of 41.2 years (SD = 11.0) and of a mean age of 26.1 years (SD = 5.5) in the EUFEST (N=303). It is important to keep in mind that during the CATIE chronic schizophrenia patients were object of the study, while in EUFEST first episode schizophrenia patients were analysed [14], hence, the differences of mean age. Other authors report of a mean age of the study participants ranging from 22 years (SD = 4) [20], 25.1 years (SD = 4.5) [21], 32 years (SD = 8.6) [15], 35.5 years (SD = 11.9) [25], 39.2 years (SD = 12.7) [12] and 63.75 years (SD = 5.53) [11]. Thus, the mean age varies widely, depending on the type of patients, first episode schizophrenia patients, or chronic schizophrenia patients to establish a rough classification. Further, the mean age depends on the focus of interest and the resultant age group. In the previous mentioned literature, age differences between the sexes were not described.
Why the mean age of our male study participants at the time of data collection has been significantly higher regarding a normal distribution than the mean age of our female participants remains unanswered for now.
Mc Cabe et al. found sociodemographic characteristics as a mean age of 42.2 years (SD = 11.4) among the study participants, a gender distribution of 34% females and 66% males respectively. Further, the patients have been receiving treatment for 15.6 years on average (SD = 10.3) and were previously hospitalized 5.2 times in the mean (SD = 7.3) [10]. These findings are partly in line with our results obtained from sociodemographic questionnaire. Mc Cabe et al.’s participants were older and males were representing two thirds of the study sample, but at the same time participants of both researches received treatment for more than 10 years (13.49 years on average in our sample between first schizophrenia diagnosis and data collection and 15.6 years on average of treatment in the present sample) as well as previous hospitalizations of 5.2 times in the mean in the present case and 8.37 (SD = 8.43) in our sample.
In both studies, the demographic and therapeutic characteristics represent the disease typical features of schizophrenia in relation to the age at initial diagnosis and the therapeutic course of the disease. In particular the chronic course of the disease and multiple hospitalisations during the course respectively as well as the higher incidence of male participants, hence males are found to be at greater risk of schizophrenia [30]. Studies by Rabinovitch et al., Morken et al., Abdel-Baki et al. furthermore found that better treatment adherence is associated with female gender. [20–22]. Following this finding, it can be deduced that men are associated with poorer adherence and hence more likely to be hospitalised or in need of outpatient treatment and are therefore more likely to be included in clinical studies. This could be an explanation why the majority of study participants in previous literature were males. Comparing
27 our results with further previous literature it stands out that the gender distribution in our sample is rather unusual. As previously shown using statistical tests, our sample does not follow a normal distribution.
No other cited paper reports of a similar gender distribution, of predominantly female participants.
Czobor et al., Jónsdóttir et al., Bodén et al. and Baloush-Kleinman et al. report of a gender distribution ranging between 54% - 73,9% male participants [9,14,16,17]. Hence our finding stands in contrast to the aforementioned study results. Van der Werf et al. found in a systematic review that men had a 1.15- fold (95% CI 1.00-1.31) greater risk of schizophrenia than women [30] as previously briefly mentioned.
The differences in prevalence should furthermore naturally lead to a higher representation of male participants in studies. This might not speak for a naturalistic design of our sample. Yet, it is possible that female patients are generally more cooperative and have higher social skills and therefore preferred to participate in our study compared to male patients.
In our sample we found that urban area residents with schizophrenia were significantly more adherent in their treatment process than rural area residents (p=0.004). Yet, the better adherence did not depend on gender, age, education, working status, age at initial diagnosis, number of hospitalizations, forms of psychotropic medication used and the participants preference of psychotropic medications formulations.
In the previous literature Bodén et al. could not find a significant association among demographic factors as sex, age, place of birth and urban area residence in a population-based cohort study [17]. This is in line with the findings of Bitter et al. who could not find a significant relationship between adherence and demographic and environmental factors as age, gender and years of education in their cross-sectional study [13]. Further Baloush-Kleinman et al. could not find significant differences between adherent and non-adherent patients related to demographic and environmental factors as sex, education, marital status, employment status, ethnicity [16]. As described, none of the previously cited papers reports of a significant association among the discussed demographic factors and better treatment adherence. We may assume that the explanation for a better treatment adherence among urban area schizophrenia ill patients is unlikely to be found among sociodemographic factors.
We found that treatment adherent schizophrenia ill patients compared to non-adherent patients had a significantly better treatment regime (behaviour) (p=0.002), a more favourable attitude towards medication and possible side effects (p=0.007), and more favourable attitude towards psychotropic medications (p=0.0001). Furthermore we found that urban area schizophrenia ill patients had significantly better attitude towards psychotropic medications (p=0.001). These findings are supported by Baloush-Kleinman et al. who showed by the use of statistical means that adherence was predicted by factors as symptom severity, awareness for the need of medication and the attitude towards medication.
They found that more positive attitudes to medication were linked to better adherence [16]. This seems to be a conclusive approach to explain the aforementioned findings of urban area schizophrenia ill patients being significantly more adherent in their treatment process than rural area residents.
28 Limitations
Our Study was of cross-sectional design. Therefore, medication adherence and potential risk factors were measured only once. Hospitalized schizophrenia patients were object of the study. A thorough analysis of the medical records has not been performed. Hence the practical implication of our results is limited.
15. CONCLUSIONS
1. The mean age of all hospitalized schizophrenia patients in our sample was 36 years (range 18- 74 years), where male participants were older than females, two thirds of study participants lived in urban areas, nearly two thirds have more than 12 years of education and were unemployed, with 23 years being the mean age at the initial diagnosis of schizophrenia and eight hospitalizations on average, 3/4 of them reported to prefer tablet medication formulation.
2. It was found that urban area residents with schizophrenia were significantly more adherent in their treatment process than rural area residents, but the adherence did not depend on gender, age, education, employment status, age at the initial diagnosis, number of hospitalizations, forms of psychotropic medication used and their preference of psychotropic medications formulations.
3. Treatment adherent schizophrenia ill patients compared to non-adherent patients had significantly better treatment regime (behaviour), a more favourable attitude towards medications and possible side effects, and more favourable attitude towards psychotropic medications.
4. Urban area schizophrenia ill patients had a significantly better attitude towards psychotropic medications.
29
16. PRACTICAL RECOMMENDATIONS
1. Future research should focus on targeted, profound, longitudinal studies in order to improve treatment outcomes and prognosis of the patients. A possibility of targeting further research is to group risk factors of medication adherence into non-modifiable and modifiable risk factors.
2. Future research should primarily focus on modifiable risk factors such as insight / illness awareness, attitude towards treatment, alcohol and drug abuse and adverse effects of antipsychotics, symptoms at baseline / severity of signs and symptoms, cognitive functioning of patients and the relationship with their medication.
3. Future treatment approaches should be more targeted and patient-focused; hence we have observed in the previous literature review that risk factors of medication non-adherence can be various.
