Factors Associated with Relapse of Schizophrenia in Bangladesh

Context: In the face of increasing number of relapse cases of schizophrenia, sufficient work is not available in Bangladesh. Aims: To find out the common factors of relapse of schizophrenia in Bangladesh and to find out the relationship of relapse of schizophrenia with sociodemographic characteristics. Settings and Design: Cross-sectional descriptive study; Department of Psychiatry, Combined Military Hospital, Dhaka, National Institute of Mental Health (NIMH), Dhaka and Psychiatry department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. Materials and Methods: Data from 50 relapse patients receiving treatment of schizophrenia were collected, from April 2018 to September 2018. Statistical Analysis Used: The data were processed and analyzed with the help of computer program SPSS (Statistical Package for Social Sciences) win version 16. Results: The mean age was 31.16 (±10.59) years ranging from 14 to 55 years. Majority of the respondents 70% (n=35) were under 35 years. 62% (n=31) of the respondents were male and 38% (n=19) were female. 96% (n=48) of the respondents were Muslims. 52% (n=26) of the respondents were married and 46% (n=23) were unmarried. 46% (n=23) were from rural background and 54% (n=27) of the respondents were from urban background. 40% (n=20) of the respondents were from lower class, 52% (n=26) were from middle class, and only 8% (n=4) were from higher class. 56% (n=28) of the respondents had perceived stressful life events and 44% (n=22) of the respondents had no such history. 52% (n=26) of the patients had experienced high expressed emotion and 48% (n=24) had low expressed emotion. Among the 50 relapsed schizophrenia patients, only 26% (n=13) had full compliance, 30% (n=15) had full noncompliance and rest had partial compliance. There was no significant relationship between educational status and medication compliance in the current study. The study revealed significant association with lower social class and presumptive stressful life events. Conclusions: This study highlighted the perceptions of schizophrenic patients and their caregivers about factors that influence relapse. It indicated that stressful life events, high expressed emotion, and non-compliance to medication had a role in relapse. This study provides information about socio-demographic and other related factors which can offer important guideline for future study. Adherence to antipsychotic medication, reducing high expressed emotion and stressful life events protect patients from relapse.


Introduction
Schizophrenia is a major mental health problem which is often difficult to manage and yet poorly understood. It afflicts a sizable population over the world. The worldwide prevalence of schizophrenia is about 1%. [1] In Bangladesh, prevalence of schizophrenia is found to be 2.4/1000 population in a detailed study of rural population adjacent of Dhaka city which is comparable with India prevalence rate. [2] Non-compliance rate with antipsychotic medication is high. Eighty percent of schizophrenia receiving antipsychotic medication fail to comply with treatment. Psychotic relapse is known to be closely linked to noncompliance to drug. Long term antipsychotic treatment has been shown to be effective in preventing relapse but even with continuous medication, about 40% of patient relapse during first year of discharge from hospital, compared with about 70% of patient taking placebo. The high rate of relapse in spite of continuous medication have stimulated research on other cause of relapse. Apart from medication non-compliance, social stressors (life events, unfavorable family atmosphere) seem to be important. The result of various studies has contributed to the development of 'relative's expressed emotion', which influence the relapse of schizophrenia. It is often accompanied by relapse even while on treatment. [3] Relapse rates vary from 50% to 92% and are similar in developed and developing countries, despite the former having wellestablished mental health services. [4] Internationally, the factors commonly associated with relapse include poor adherence to treatment, substance abuse, co-morbid psychiatric illness, a co-morbid medical and/or surgical condition, stressful life events, and the treatment setting. [5] this study is designed to assess the factors associated with relapse of schizophrenia in Bangladesh.

Materials and Methods
This cross-sectional descriptive study was conducted from April 2018 to September 2018 at Department of Psychiatry, Combined Military Hospital, Dhaka, National Institute of Mental Health (NIMH), Dhaka and Psychiatry department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka. For demographic assessment, a semi-structured questionnaire was prepared by the interviewer after taking informed written consent. A series of 50 relapse patients of schizophrenia was taken by purposive convenience sampling method. Data was processed and analyzed with the help of computer program SPSS (Statistical Package for Social Sciences) windows version 16. Quantitative data was expressed as mean and standard deviation and qualitative data as frequency and percentage. Comparison was done by Chi-Square (χ 2 ) test and unpaired t-test where necessary. Risk factors was determined using Odd Ratios.

Results
The mean age of the study group was 31.16 (±10.59) years ranging from 14 to 55 years. Majority of the respondents (70%) were under 35 years. Distribution of respondents according to sex revealed that 62% of the respondents (n=31) were male and rest 38% were females (n=19). The educational status of the respondents was found about 8% were illiterate, 4% were below class five, 24% were studied from class six to ten, 52% were attained SSC and HSC and 12% had graduated and above. One in four respondents were unemployed, 30% were student, 24% were housewives, 16% were service holder and 6% were farmer. The marital status of the respondents revealed 52% of the respondents were married and 46% were unmarried.
The study also revealed the perceived stressful life events among the respondents. About 56% of the respondents had stressful life events and rest (44%) had no such history. Distribution of stressors among the study population is shown in Table 1.
The study found out the distribution of expressed emotion in the family of the relapsed schizophrenic patients. About 52% (n=26) of the respondents had high expressed emotion. It also explored the relationship of family history of mental illness with expressed emotion which found no significant association with history of mental illness with expressed emotion.
The distribution of high expressed emotion along with family history of psychiatric illness is shown in Table 2. Distribution of presumptive stressful life events and compliance among the respondents is shown in Table 3. The study found that, among the 50 relapsed schizophrenia patients, only 26% had full compliance, 30% had full noncompliance and rest (44%) had partial compliance.

Discussion
Schizophrenia is a chronic and disabling illness, with the majority of patients experiencing multiple relapses during the course of the illness. Relapse increases the economic burden on health care systems because of its associated morbidity and re-admissions to hospital. Prevention of relapses could have significant therapeutic and socio-economic implications. Causes of relapse is noncompliance to drug, loss of medication efficacy, high expressed emotional relative and stressful life events. Multiple factors contribute to increasing the risk of relapse. In a systematic review and meta-analysis of longitudinal studies it was found that non-adherence with medication, carers' criticism and poorer premorbid adjustment significantly increased the risk for relapse in firstepisode psychosis. [6]  According to analysis the mean age was 31.16 (SD±10.59) years ranging from 14 to 55 years. Majority of the respondents (70%) were under 35 years. Distribution of relapse case respondents according to sex revealed that 62% of the respondents were male and rest were females. One study showed Schizophrenia is generally reported to be slightly more frequent in men than in women, with a risk ratio of 1.4/1. The disorder is also more severe in men. [7] In addition, men tend to develop severe schizophrenia earlier than women; the peak age of onset of frank psychotic symptoms is 20-24 years in men, but 5 or more years later in women. [8][9][10] Distribution of religion of the respondents revealed 96% of the respondents were Muslims. The educational status of the respondents was found about 8% were illiterate, 4% were below class five, 24% were studied from class six to ten, 52% were attained SSC and HSC examination, and 12% had graduated and above.
The occupational status was found about one in four respondents were unemployed, 30% were student, 24% were housewives, 16% were service holder and 6% were farmer.
The marital status of the respondents revealed about 52% of the respondents were married and 46% were unmarried.
Residence of the respondents was found 46% were from rural background and 54% of the respondents were from urban background. Schizophrenia is most common in disadvantaged areas of inner cities, a finding first noted in Chicago in 1939. This association was recently replicated in an epidemiological study in England, the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study, which reported that the incidence of schizophrenia in the smaller cities of Nottingham and Bristol was less than half of that in London.
The highest rates of people with schizophrenia in London were in areas with the lowest social cohesion, a finding that was also reported in the original Chicago study. [11,12] Here 40% of the respondents were from lower class, 52% were from middle class, and only 8% were from higher class. Relapse in lower and middle social class might be due to poor economic condition, social stigma and ignorance.
In the study found that among the 50 relapsed schizophrenia patients, only 26% had full compliance, 74% had noncompliance. The rate varied from different studies and in Egypt it was 74%. [13] Another study in Bangladesh depicted about 87% of the respondents were non-compliant to medications which can be explained by psychopathology of the disorder itself, poor health literacy, and poor status of psychoeducation. [14] After 1-2 years of being well on antipsychotic medication, the risk of relapse remains high (figures of 10-15% per month have been quoted), but this area is less well researched. [16] Other studies in first episode patients have found that discontinuing antipsychotics increases the risk of relapse 5-fold and confirmed that only a small minority of patients who discontinue remain well 1-2 years later. [16][17][18][19][20] A comprehensive review 73 reported that the rate of medication non-adherence in patients with schizophrenia is as high as 40%-50%.
In this study 5 revealed the medication compliance affectivity by the educational attainment on the respondents. There was no significant relationship between educational status and medication compliance in the current study.
The factors consistently associated with non-adherence in patients with schizophrenia are lack of insight, attitudes towards their illness and the medication, past experiences with their illness and its treatment, substance abuse, adverse drug reactions and lack of social support. [21][22][23] The distribution of expressed emotion in the family of the relapsed schizophrenic patients revealed about 52% had high expressed emotion and 48% had low expressed emotion. Previous studies found that prevalence of high expressed emotion in urban London and California were 57% and 67% respectively, but 23% in India. [24] Expressed emotion has been extensively studied and has been found to be a robust and significant predictor of relapse in schizophrenia. [25] The study explored the relationship of occupation with expressed emotion. The current study revealed no significant association of occupation with expressed emotion. This study also explored the relationship of family history of mental illness with expressed emotion. The current study revealed no significant association with history of mental illness with expressed emotion.
The distribution of perceived stressful life events among the respondents was fond about 56% of the respondents had stressful life events and rest of the respondents had no such history.
People with psychosis also report an increased rate of particularly intrusive life events, such as assault, before the onset of illness. [26] Whether these environmental factors are independent risk factors is debated.
The relationship of social class with presumptive stressful life events, the current study revealed significant association with lower social class and presumptive stressful life events where p=0.016 (revealed by Chi square test). One of the important factor is stressful life event which can relapse schizophrenia. People with schizophrenia are subject of many adverse effects from the social environment, which upset their social adaptation. [27] This is a prerequisite, for a life in a chronic stress with the all following consequences, mostly related to the progress of the schizophrenia.
Development of concomitant diseases and higher mortality rate. [28] There are studies that indicate that people with schizophrenia are more vulnerable from the impact of the social stress in comparison with mentally healthy people. [29] These studies correlate with others similar to them and thus show the relation between stressful factors and the severity of the clinical manifestation of the disease. [30] From the other side there are opinions that because of the disease and the related with it "perception of the world" these patients are distant from the social failures and respectively they don't show the expected "poor" quality of life. [27]

Conclusion
This study highlighted the perceptions of patients with schizophrenia and their caregivers about factors that mostly influence relapse. Despite recent therapeutic progress, relapse in schizophrenia is a common and major problem among Bangladeshis. The study indicated that stressful life events, high expressed emotion, and non-compliance with medication had a role in schizophrenic patients for its relapse. This study provides information about socio-demographic and other related factors which can offer important guideline for future study.