ACKNOWLEDGEMENT
This study was completed with a variety of help from my family, friends, colleagues, and especially my supervisor. First of all, words cannot express my gratitude to my Professor Jenny Wu Chia-Yi for her valuable patience and feedback, I would not have started digging into the importance of treatment-resistant depression in suicide research. Her consistent support and caring and her beautiful family engagement have helped me go through the most challenging stage of PhD study.
Throughout the course of study, Professor Jenny provided endless effort in reviewing my work. Her efficiency and effectiveness are the essential part that ensured my study progress. I am proud to be one of her students and honored to have worked with her during my PhD journey. I owed my most profound gratefulness to her.
I also could not have undertaken this journey without my dissertation committee: Professor Ming-Been Lee, Professor Bih-Ching Shu, Professor Jin-Ru Rong, Professor Li-Yu Daisy Liu, and Professor Shu-Sen Chang, who generously gave me insightful comments, support and encouragement from my proposal defense to my dissertation defense. Especially, Professor Ming-Been Lee who always encourage and fully support me during research progress.
During the process of data collection, thanks to all the leaders, psychiatrists, and psychiatric nurses who helped me set up a procedure for follow-up and acquire research information from National Institute of Mental health, Bach Mai hospital.
Many thanks to translators and expert panel for their fantastic collaborative work:
N.P.A.Ha, D.T.Ha, N.T.Son, N.T.Tuyet, N.T.T.Minh, V.S.Tung, P.T.T.Hien, N.T.P.Huy, D.T.Mai, N.T.Tam. On the other hand, many people contributed to the data collection included patients and their caregivers, without their commitment this study would not be completed. Further, while I stayed in Taipei for studying, I had a lot of supports and encouragements from the President of Hanoi Medical University as well as Leaders and colleagues of Faculty of Nursing and Midwifery, Hanoi Medical University.
My special thanks go to other Professors of the School of Nursing, College of Medicine, National Taiwan University, including Dean Professor Wen-Yu Hu – who kindly accepted me as the first International Ph.D. student in this Department and supported me from the first day I arrived at the school. Thanks to Professor Yeur-Hur Lai, Professor Meei-Fang Lou, Professor Fei-Hsiu Hsiao, Professor Bih-Shya Gau, Professor Chia-Hui Chen, Mrs. Hui-Yu Lee, Mrs. Su-Yi Chen, name a few. I am so proud to be an NTUCM student, and I especially appreciate the University giving full scholarship to fulfill my Ph.D. dream. Furthermore, I am grateful to all the University’s and college’s administrative staffs, VSANTU, and friends in Taiwan. I appreciate their support in every aspect that kept me moving forward and solved many difficulties during the study process. Moreover, my gratitude goes to Professor Duujian-Tsai, Dr. Happy Kuy-Lok Tan, Mrs. Yuchia Chen, and Dr. Adrian Coombs for their generous encouragement during my study in Taiwan.
Additionally, this endeavor would not have been possible without my family's extraordinary support for more than three years. This thesis is dedicated to my dad (Pham Van Quy) and my pass-away mom (Nguyen Thi Thom), who continuously
supported and believed in me throughout my life. Mom, I know you can witness this moment with me. I am grateful to my brothers (Pham Nguyen Thanh Tung and Pham Nguyen Bach) and their families always send encouragement and are on my side.
Thanks to my sister-in-law (Chu Vu Ngoc Hang) has spent unconditional love to look after my two daughters, with smiles and love. Thanks to my mother-in-law (Vu Thanh Van) and my auntie (Nguyen Thi Thao), who always encouraged my family during our most challenging times. Moreover, special thanks to mom – Dr. Julie Millenbrunch, who supported me during my master's degree and continuously encouraged me to go through this journey as one of my family members.
I am most grateful to my beloved husband – Chu Vu Hieu, who can accept every aspect of me and support me with all his heart during my life, especially for this Ph.D. journey. His positive actions have taught me a lot even in the worse situation. Last but no means the least, to my two sweetie daughters, Chu Pham Gia Han (Miu Miu) and Chu Pham Kha Han (Ke). I am so proud to be your mom and thank you for giving me a chance to be a better person in everyday life. Without you, I would not make this dream come true.
Finally, I thank myself, who have not given up during this long and challenging journey. Keep up the good work in the next step.
PUBLICATIONS RELATED TO THE PHD DATA
1. Huong, P. T. T., Wu, C. Y., Lee, M. B., Tuan N. V., Hien, P. T. T., Tung, D. T., Tung V.
S., & Son, N. T. Longitudinal asociation between psychological factors, community integration, and suicide risk among patient with treatment-resistant depression in Vietnam. General Hospital of Psychiatry. (UNDER REVIEW)
2. Huong, P. T. T., Wu, C. Y., Lee, M. B., Tuan N. V., Hien, P. T. T., Tung, D. T., Tung V.
S., & Son, N. T. Suicidality trajectory, hopelessness, resilience, and self-efficacy among patients with Treatment-resistant Depression in Vietnam. Journal of Nursing Research.
(UNDER REVIEW)
PUBLISHED/UNDER-REVIEW WORKS PARTICIPATED DURING PHD 1. Huong, P.T.T, Yeh, C. M, Wu, C. Y., Lee, M. B. (2022). Nursing policy
recommendations in a suicide prevention training program for the nurses: a perspective from Vietnam. Journal of Suicidology, vol 17 (3): 232-237. Doi:
10.30126/JoS.202209_17(3).0007.
2. Huong, P. T. T., Wu, C. Y., Lee, M. B., Hung, W. C., Chen, I. M., & Chen, H. C. (2022).
The influence of research follow-up during COVID-19 pandemic on mental distress and resilience: A multicenter cohort study of treatment-resistant depression. International Journal of Environmental Research and Public Health, 19(6), 3738.
https://doi.org/10.3390/ijerph19063738
3. Huong, P. T. T., Wu, C. Y., Lee, M. B., & Chen, I. M. (2022). Associations of suicide risk and community integration among patients with treatment-resistant depression.
Frontiers in Psychiatry, 13, 806291. https://doi.org/10.3389/fpsyt.2022.806291.
4. Huong, P.T.T., Hien, P.T.T., Son N.T., Ngoc, N.T.M. (2021). Family-based intervention for suicide prevention in adolescenses: a systematic review. Journal of Nursing Science, 4(1), 2615–9589. https://jns.vn/index.php/journal/article/view/313.
5. Wu, C.Y., Lee, M.B., Huong, P.T.T., Chen, I.M., Chen, H.C., & Hsieh, M.H.
Longitudinal outcomes of resilience, quality of life, and community integration in treatment-resistant depression: A two-group matched controlled trial. Journal of the American Psychiatric Nurses Association. (UNDER REVIEW)
6. Ko Y.Y, Wu C.Y, Lee M.B, Huong P.T.T, Chen H.C. The psychosocial characteristics and suicide risks among patients with treatment-resistant depression. (2022). Journal of Suicidology, 17 (4), 399-407. https://doi.org/10.30126/JoS.202212_17(4).0012.
7. Huong N.T.T, Ly D.T.K, Huong P.T.T, Anh H.P, Hoa T.T, Huyen N.T.H. The symptoms of postpartum depression observed by family members: a pilot study. (2022).
Frontiers in Psychiatry, 13:897175. doi: 10.3389/fpsyt.2022.897175.
8. Wu, C.Y., Lee, M. B., Huong, P. T. T., Chan, C. T., Chen, C. Y., & Liao, S. C. (2022).
The impact of COVID-19 stressors on psychological distress and suicidality in a nationwide community survey in Taiwan. Scientific Reports, 12(1), 2696.
https://doi.org/10.1038/s41598-022-06511-1.
9. Wu S., Rolfes R., Clarke C., Smith A., Thanh D.V, Thu B.M, Giang N.T.H, Anh N.T.L, Huong P.T.T, Hien P.T.T, Odonnell R.R. Integrated behavioral health care in Vietnam:
Examples from the Hanoi Bach Mai Hospital of patients with hypertension. (2022)
Asian Journal of Health Sciences, 8(1), ID28.
Doi:https://doi.org/10.15419/ajhs.v8i1.499.
10. Lu, M. J., Li, J. B., Wu, C.Y., Huong, P.T.T., Hsu, P.C., & Chang, C.R. (2021).
Effectiveness of a sexual health care training to enhance psychiatric nurses' knowledge, attitude, and self-eEfficacy: A quasi-experimental study in southern Taiwan. Journal of the American Psychiatric Nurses Association, 10783903211045733. Advance online publication. https://doi.org/10.1177/10783903211045733.
ABSTRACT
Introduction: Patients with treatment-resistant depression (TRD) have higher rates of suicidal ideation and a higher prevalence of suicide attempts than patients with other diagnoses related to depressive disorders. However, studies related to the TRD population and suicide are scared in Vietnam. Therefore, this study sought to examine the short-term fluctuation of suicidality and the longitudinal association of psychological factors and community integration with recent suicide ideation and attempts from hospitalization to a 3-month post-discharge period among patients with TRD in a leading national hospital in Hanoi.
Methods: A prospective study design with 3-month followed-up from hospital to the participants’ community. All 53 patients with TRD were interviewed one week after admission (T0) plus 1-week (T1), 1-month (T2), and three months (T3) post- discharge interviews with a structured questionnaire from October 2021 to September 2022. Descriptive analyses were performed to characterize sociodemographic and trend analysis. Repeated measures with ANOVA were applied to find the significance between the time factor and within–factor effects of repeated measures over the major outcome. Further, the Generalized estimation equations (GEE) were used to identify factors associated with recent suicide ideation/attempt during throughout the study period.
Results: The trend of suicidality varied across the four-time points. The downward trend of suicidality at T0 and T1 reflected the initial effects of inpatient treatment;
however, an upward trend was observed during the 3-month follow-up period. Nearly half of the participants (46%) reported recent suicide ideation, and 13.46% attempted
suicide at T3. Antidepressant overdose was the most common suicide method among the participants. While the suicide attempt rate was found to be a significant difference only with T0>T1, suicide ideation and suicide intention were also found to be significantly different (T0>T1, T2, and T3). However, there was no significant difference between T1-3 interviews during the follow-up. Overall, the community integration performance increased after discharge compared to the time of admission (T0<T2, T3, p<0.05) and post-discharge one week (T1<T2, T3, p<0.05). The total score of psychological distress (BSRS-5) showed a reduction after treatment from hospitalization with a significant change from T0 compared to one-week (T1) and one-month (T2) after discharge, but the effect did not show significance compared to 3-month post-discharge period (T0>T1, T2, p<0.05). In addition, the hopelessness score reduced significantly after discharge compared to three follow-up periods (T0>T1, T2, T3, p<0.05). In our observations, most of the participants exhibited a low level of resilient coping, quality of life, self-rate self-efficacy, and recovery but with signs of improvement (T0<T1, T2, T3, p<0.05). An overall decrease in self- reported adherence was observed after discharge, with a significant difference between T1 and T2 compared to T0 (T0<T1, T2, p<0.05).
In the Generalized estimation equations (GEE) analysis, high level of psychological distress and hopelessness significantly associated with suicide ideation (1.35-point and 1.28-point) and suicide attempt (2.59-point and 2.41-point) respectively throughout the study period. Moreover, one score lower in community integration increased the risk of suicide ideation during follow-up by 12%. Among
significantly correlated with suicide ideation and attempt. In our observation, male participants revealed a higher risk for suicide ideation by 4.10-fold but lower risk for attempted suicide by 5.26-fold compared to females. Patients who reported a religious belief had a lower odds ratio for suicide ideation by 4.55-fold. Notably, with one-year younger, the risk for suicide attempt among the TRD patients increased by 9% during the study period.
Conclusion: Suicidality fluctuated between the in-hospital treatment phase and the first three months following discharge in a group of patients with TRD in this study, with high psychological distress, hopelessness, low community integration, gender, younger age, and no religious belief being the top factors contributing to suicide risks.
The findings highlighted the need for regular patient monitoring and assessment after discharge to identify those with TRD at high risk of suicide. The interventions improving psychological distress, hopelessness, and community integration for suicide prevention in the short-term after psychiatric hospitalization deserve more attention. Psychiatric professionals should help those with TRD to improve and maintain their stress management skills, feelings of hope, and life integration in the community, with a particular focus on gender-specific policy (e.g. female suicide attempt and male suicide ideation follow-up care) and those who are younger. Nursing professionals working in non-psychiatric fields of community or hospital settings also play the key role of gatekeepers for early engagement and referral of high-risk patients with depression and comorbid chronic physical conditions.
Keywords: Treatment-resistant depression, follow-up, community integration, suicide ideation, suicide attempt, psychological distress
TABLE OF CONTENTS
ACKNOWLEDGEMENT... iii
PUBLICATIONS RELATED TO THE PHD DATA ... vi
ABSTRACT ... viii
LIST OF TABLES ... xv
LIST OF FIGURES ... xvi
CHAPTER 1 ... 1
INTRODUCTION ... 1
CHAPTER 2 ... 3
LITERATURE REVIEW ... 3
2.1. Treatment-resistant depression ... 3
2.1.1. Introduction of depression and treatment-resistant depression ... 3
2.1.2. Definition of treatment-resistant depression ... 4
2.1.3. Current treatment modalities ... 10
2.1.4. The burden of treatment-resistant depression ... 12
2.2. Treatment-resistant depression and suicide risk factors ... 13
2.2.1 Concept of suicidality ... 13
2.2.2. Treatment-resistant depression and suicide risk factors ... 15
2.3. Miscellaneous risk/protective factors for suicide in the community... 22
2.3.1. Community integration ... 22
2.3.2. Family support ... 25
2.3.3. Resilience ... 26
2.4. Current development of depression and suicide care in Vietnam ... 27
2.4.1. Introduction of the general health care service ... 27
2.4.2. Mental health care system in Vietnam ... 28
2.4.3. Epidemiology of depression and suicide prevention in Vietnam ... 29
2.4.4. Psychiatric and mental health nursing care in Vietnam... 32
2.5. The effect of COVID-19 during the research procedure ... 33
CHAPTER 3 ... 35
STUDY OBJECTIVES AND HYPOTHESES ... 35
3.1. Study objectives ... 35
3.2. Hypotheses ... 35
3.3. Research framework ... 37
CHAPTER 4 ... 38
METHODOLOGY ... 38
4.1. Study design ... 38
4.1.1. Setting ... 38
4.1.2. Eligibility ... 39
4.1.3. Power calculation ... 40
4.2. Data collection procedure ... 42
4.3. Measurements ... 43
4.3.1. The socio-demographic information ... 43
4.3.2. The five-item Brief Symptoms Rating Scale (BSRS-5) ... 44
4.3.3. Suicidality ... 45
4.3.4. Hopelessness ... 46
4.3.5. The Revised Community Integration Questionnaire (CIQ-R) ... 46
4.3.6. Family support ... 48
4.3.7. The Brief Resilient Coping Scale (BRCS) ... 48
4.3.8. EuroQoL 5-Dimensions 5-Levels (EQ-5D-5L) ... 49
4.3.9. The Patient Health Questionnaire (PHQ-9) ... 50
4.4. The translation and validation of selected questionnaires process ... 50
4.5. Data analysis ... 59
4.6. Ethical considerations ... 60
4.7. Quality control ... 61
4.8. Time frame for research process ... 62
CHAPTER 5 ... 64
RESULTS ... 64
5.1. Response rate ... 64
5.2. Socio-demographic characteristics ... 65
5.3. Short-term fluctuation of suicidality during hospitalization to 3-month post- discharge ... 69
5.4. Trend analysis and follow-up results... 73
5.4.1. Community integration change through-out follow-up periods ... 73
5.4.2. Psychological factors change during follow-up period ... 76
5.4.3. Pearson correlation of study variables during the four time points ... 88
5.5. Association between psychological factors and community integration with recent suicide ideation during follow–up period ... 91
5.6. Association between psychological factors and community integration with recent suicide attempt during follow – up period ... 91
CHAPTER 6 ... 97
6.1. Suicidality fluctuation during follow-up period... 97
6.2. Community integration and suicide risk ... 99
6.3. Psychological factors and suicide risk ... 100
6.3.1. Psychological distress ... 100
6.3.2. Hopelessness ... 102
6.3.3. Resilient coping skill ... 103
6.3.4. Quality of life ... 104
6.3.5. Self-rated recovery and self-efficacy ... 105
6.4. Socio demographic and suicide risk ... 106
6.4.1. Gender ... 106
6.4.2. Age ... 108
6.4.3. Religious belief... 109
6.5. Strength and limitation of the study ... 110
6.6. Implications... 111
CHAPTER 7 ... 116
CONCLUSION... 116
APPENDIX ... 117
REFERENCES ... 124
LIST OF TABLES
Table 1. Summaries of treatment-resistant depression definition ... 7
Table 2. Measurements and the assessment time points ... 43
Table 3. The relevance rating on the item scale for CIQ-R ... 55
Table 4. The relevance rating on the item scale for BSRS-5 ... 55
Table 5. The relevance rating on the item scale for BRCS ... 55
Table 6. Gender and age of the sample participated in validation process ... 56
Table 7. Internal consistency, test-retest reliability of CIQ-R, BSRS-5, and BRCS ... 56
Table 8. Mean scores of CIQ-R, BSRS-5, and BRCS among two test groups ... 57
Table 9. Bivariate correlation between CIQ-R, BSRS-5, and BRCS with criterion variables (N=254) ... 57
Table 10. Overall socio-demographic characteristics of the participants at baseline (N = 53) ... 67
Table 11. Medical visit characteristics among participants ... 68
Table 12. Suicidality of the participants during hospitalization to 3-month post-discharge 71 Table 13. Suicide attempt methods used ... 72
Table 14. Community integration change during hospitalization to 3-month post-discharge ... 74
Table 15. Psychological distress change during hospitalization to 3-month post-discharge 77 Table 16. Resilient coping skill change during hospitalization to 3-month post-discharge 81 Table 17. Quality of life change during hospitalization to 3-month post-discharge ... 83
Table 18. Self-rated adherence, self-efficacy, and recovery changes during hospitalization to 3-month post-discharge ... 86
Table 19. Pearson correlation of study variables during the four time points... 89
Table 20. Generalized estimation equations analysis for recent suicide ideation during hospitalization to 3-month post-discharge ... 93
Table 21. Generalized estimation equations analysis for suicide attempt during hospitalization to 3-month post-discharge ... 95
LIST OF FIGURES
Figure 1. A continuum of suicidality ... 15
Figure 2. The mental health services in Vietnam ... 31
Figure 3. Research conceptual framework ... 37
Figure 4. Data collection procedure ... 42
Figure 5. Instrument validation procedure ... 58
Figure 6. Time frame for research process ... 63
Figure 7. Trajectory of suicidality among patient with TRD ... 72
Figure 8. Community integration change during hospitalization ... 75
Figure 9. Community integration total change during hospitalization ... 75
Figure 10. Psychological distress change in item during hospitalization to 3-month post discharge... 78
Figure 11. Psychological distress changes during hospitalization... 78
Figure 12. Hopelessness change during hospitalization ... 79
Figure 13. Resilient coping skill total score change during hospitalization... 80
Figure 14. Quality of life (EQ-5D-5L) change in item during hospitalization to 3-month post-discharge follow-up period ... 84
Figure 15. EQ-5D-5L and EQ-VAS change during hospitalization ... 84
Figure 16. Self-rated adherence, self-efficacy, and recovery change ... 87
Figure 17. Family support change during hospitalization to 3-month post-discharge ... 88
CHAPTER 1
INTRODUCTION
Globally, major depressive disorder (MDD) is the third leading cause of years lived with disability (James et al., 2018) and accounted for the highest proportion of disability-adjusted life years (DALY), 5.55 time higher in low and middle-income countries to high-income countries (Collins et al., 2011). In addition, MDD is the primary cause of disability for chronically ill patients living in the community, as well as the major risk for suicide (Kessler & Bromet, 2013; Omary, 2021). The number of individuals with depression is approximately 350 million people worldwide; of that, 76% - 87% of people in low -and middle-income countries received no treatment (WHO, 2017). Even after adequate treatment, the long-term course for MDD is still highly relapsing and recurrent (Sim et al., 2015).
Despite the lack of treatment-resistant depression (TRD) definition acceptance globally, TRD has been most commonly recognized as not responding to at least two antidepressant medication regimens of an adequate dose and duration for MDD patients (Gaynes et al., 2020). TRD occurs commonly in up to 30% of treated MDD patients, resulting in decreased quality of life, functional impairment, productivity loss, comorbidities, and treatment cost (Al-Harbi, 2012). Significantly comparing to non-TRD patients, the TRD group has significantly increased the risk of mortality or suicide with 29-35% higher all-cause mortality and two-fold suicide
The challenge of long-term effects of functional impairment, high recurrence, and prominent suicidal risks among patients with TRD require a holistic-care approach for patients in both hospitals and community settings. In this context, mental health professionals have addressed the key domains included in home and family life, productivity, and social activities, which affect the individual levels of community integration among patients with MDD (Wu et al., 2016). Many authors have gradually expanded the definition of community integration over the years, but most include three domains that are widely viewed as integral to the concept:
productivity, social activity, and independent living (Migliorini et al., 2016).
Following the suicide prevention perspective, well-integrated life in the community was associated with a reduction of current suicide ideation (Kachadourian et al., 2019), and is an important concept that affected on the individual level of recovery for patients with MDD (Bennabi et al., 2015; Wu et al., 2016). However, to design appropriate strategies, the correlation between life integration and suicide risks was unclear and worth further investigation.
To date, there is little known about the characteristics of Vietnamese patients with TRD and risk/protective factors related to community integration, which is important for future direction in supporting patients during the recovery process in term of disease management and suicide prevention. Especially there is a deficit of research on this area in Vietnam. Therefore, this study investigated the community integration level and suicide risk among people with TRD before and after hospital discharge at the National Institute of Mental Health – Bach Mai hospital.
CHAPTER 2
LITERATURE REVIEW
2.1. Treatment-resistant depression
2.1.1. Introduction of depression and treatment-resistant depression
Major depressive disorder (MDD) is a common mental disorder and a significant public health issue affecting approximately 300 million people globally (WHO, 2017). The lifetime prevalence of depression for men and women about 5- 12% and 10-25% respectively (Mackenzie et al., 2005). According to a return-on- investment analysis to calculate the treatment costs and health outcomes for depression and anxiety across 36 countries between 2016-2030 (Chisholm et al., 2016), researchers found a 5 to 1 return on investment for depression, when accounting for both healthy life years gained and economic return on productivity.
They also estimated that left untreated, MDD can lose 50 million years of work globally annually, which was valued at over $925 billion (Chisholm et al., 2016), and may lead to severe consequences with a lifetime suicide risk of 2.2–15% (American Association of Suicidology, 2014).
Despite the modern era of psychiatry development, MDD is still not fully understood with a complexity and heterogeneity in trajectory of disease and pathophysiology (Li et al., 2021). According to the 5th Diagnostic and Statistical Manual of Mental Disorders (DSM-5, 2013) MDD is characterized by depressive
mood, markedly diminished interest or pleasure, low energy, increase or decrease in weight or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue or loss of energy, a sense of worthlessness or inappropriate guilt, impaired thinking or concentration, or indecision, and recurrent thoughts of death. At least five of the above symptoms must be present during the same two-week period and represent a change from previous functioning; one of these symptoms must be either a depressed mood or a loss of pleasure or interest. Diverse symptom combinations may impact the accuracy of MDD diagnosis, leading to a variety of pharmacologic and non-pharmacologic treatments for MDD (Cipriani et al., 2009; Han et al., 2020).
The goals of MDD treatment are to control symptoms, achieve remission and assist patients in recovery functioning level. However, up to 30% of patients with MDD do not respond to a typical antidepressant medication, which is termed treatment-resistant depression (TRD) (TRD) (Al-Harbi, 2012). TRD is a complex disease that reflects various depressive subtypes, its feature of psychiatric and physical comorbidity results in a significant burden to the patients themselves, their families, and especially to the psychiatric and primary care systems (Al-Harbi, 2012;
Rush et al., 2006).
2.1.2. Definition of treatment-resistant depression
“Treatment-resistant” does not mean that depression cannot be treated, but rather that it does not respond immediately to standard treatment (Bschor et al., 2014).
The most common definition of TRD is an “inadequate response to adequate
antidepressant trials”, which appeared in all of the literature. Antidepressant failure can be defined as a failure to achieve remission or, more practically, as a 50%
improvement in depressive symptoms or inability to return to work/study, as confirmed by a clinical instrument (Han et al., 2020). However, a recent review shows that there is no consensus definition existed for TRD (Gaynes et al., 2020). Primarily, there appeared to be variation in clinical practice regarding the definition of TRD between Europe, the US, and Asia (Ng et al., 2019). To date, the concept of TRD is rarely discussed as well as research on Vietnamese mental health services. To reduce the variability in how TRD is defined and the misclassification of non-TRD patients, it is essential to adopt a universal standard definition for TRD that is also compatible with Asian culture. A universal definition would benefit clinical and research settings by facilitating data comparisons between settings (Trevino et al., 2014). Therefore, to have an appropriate definition for the current study, we conducted a synthesis of the TRD definition by searching reviews and experts’ consensus to understand the most updated standard definition in recent ten years from 2012 to 2022 (as can be seen in Table 1).
Despite the varied definition across the world with a lack of a uniform definition, the most commonly used definition of TRD from 1983 to 2013 was
“failure of at least two antidepressants with adequate trials (McIntyre et al., 2014). A recent two reviews and consensus among the Asian population defined TRD as the failure of at least two antidepressant trials at an adequate dose for 6–8 weeks during any MDD episode (Han et al., 2020; Ng et al., 2019). However, recent reviews and
consensus from Canada (Rybak et al., 2021), European countries (Sforzini et al., 2022), and South East Asian region (Indonesia, Malaysia, Philippines, Singapore, and Thailand) (Tor et al., 2022) defined TRD as the failure of at least two antidepressants with adequate dose and duration for at least 4-6 weeks, 4-week, and 4-8 weeks, respectively. Hence, the minimal effective dosage must be given for at least 4 weeks in order to meet the criterion of sufficient dose and duration. In real-life situations, up to 58% of Asian physicians would treat their patients for 4-8 weeks before determining antidepressant failure (Han et al., 2020); this is consistent with the situation in Vietnam. Therefore, we used the definition of TRD as the “failure of at least two antidepressants with adequate dose and duration a 4-8 weeks duration” in the present study. Further, The Maudsley Staging Method (MSM) (Fekadu et al., 2018) was used to assess the duration of illness, symptom severity (as defined by the fourth position in ICD-10 diagnoses of MDD), and treatment-refractory status with a history of antidepressant failures or augmentation. The research team used a defined TRD threshold of ≥5 scores in MSM to identify TRD patients (Hägg et al., 2020).
Table 1. Summaries of treatment-resistant depression definition Researchers/
Year
Type of review
Regions Definition of TRD Limitation
(Tor et al., 2022)
Consensus
of 13
psychiatrists in South East Asian region
South East Asia
(SEA)
Suggest change the term TRD to
““pharmacotherapy-resistant
depression” (PRD) which is a more suitable term for TRD. PRD is defined as “failure of two drug treatments of adequate doses, for 4–8 weeks duration with adequate adherence, during a major depressive episode”.
Not offer advice on dosage or medications because access to and availability of treatment options varies across the SEA area.
(Sforzini et al., 2022)
Delphi- method- based consensus approach
TRD is used to describe people whose MDD severity has decreased by less than 25% with depression scale measurements while taking at least two antidepressants, and PRD is used to describe people whose MDD severity has decreased by between 25% and 50%
while taking at least one antidepressant.
Sufficient dose and duration of at least 4 weeks.
Weak consensus about previous antidepressant treatments. Only judgment from clinical and professionals without any hard and objective validation. So narrow group between TRD and PRD
(Rybak et al., 2021)
Literature review 1998–2020;
Delphi process with 18 Canadian expert consensuses
All TRD should be defined as the lack of response to two adequately dosed and supported by evidence antidepressant trials. Minimum trial duration for antidepressants should be defined as 4–
6 weeks.
Nonresponse defined as less than 50%
symptom reduction (HAMD‐17).
There are no specific assessment tools that are specifically
recommended by this group of experts to be used in TRD.
260 articles 1995 – 2019
criteria: one or more, two or more, and three or more treatment failures.
For BD require one prior treatment failure.
No clear consensus emerged on defining adequacy of either dose or duration, but minimum duration cited is 4 weeks.
inclusion criteria in recent TRD studies to confirm systematically an adequate dose or duration has not previously been described.
(Han et al., 2020)
Consensus from 246 clinicians in Asian countries
Hong Kong, Japan, Mainland
China, South Korea, Taiwan
A TRD diagnosis also necessitates 2 qualifying antidepressant failures within the same depressive episode, from the same or different classes, and achieving the minimum effective antidepressant dose for 6–8 weeks.
Antidepressant failure can be defined as a failure to achieve remission or, more practically, as 50% improvement in depressive symptoms (HAM-D or MADRS) or inability to return to work/study, as determined by a clinical tool.
Self-rate scale as PHQ-9/ QIDS-16 may be acceptable if time constraints.
Even among experts, there is little agreement as to how TRD should be defined and how such patients can be identified in actual clinical settings.
(Ng et al., 2019)
Systematic review and panel
discussion;
Ten
guidlines, 89 studies, 2010 – 2016
Asia- Pacific
region
Failure of at least two antidepressant trials at a sufficient dose for 6–8 weeks in patients with MDD.
Treatment failure was defined as a lack of complete remission (i.e. non- remission) with an appropriate treatment dosage and trial duration; and measured as a HAM-D score of >7 or a MADRS
Few studies provided clinically relevant definitions of TRD, and a limited number of nations were represented in the included studies and expert panel.
response as failure, as measured by a HAM-D or MADRS scale decrease of 10% to 20%. In APAC research settings, a reduction in HAM-D of less than 50 percent was regarded as a lack of response.
(Brown et al., 2019)
Systematic review and qualitative interviews;
150 articles from inception until
December 6, 2017.
All 50.3% of 155 definitions specified requirement of at least 2 treatment failures.
Another has defined more than 3 treatment failures.
Qualitative interview with 6 Canadian mental health professionals (psychiatrists, clinical researchers, nurses, coordinators) defined: failures of an adequate trial of at least 2 - 3 antidepressant medications and an adequate trial of psychotherapy (10-12 weeks by quantified practitioner).
TRD definition is not universally accepted. In both research and practice, there is a disconnect between concept and definition.
In practice, individual-level and patient-focused terminology, such as "complex" and "struggled throughout their life," is
employed, and non-
pharmacologic therapies must be adequately trialed before these terms are used.
(McIntyre et al., 2014)
Review;
1983 – 2013
All Failure to achieve remission with 2 or more adequate antidepressant trials defines TRD
TRD has been studied less frequently than non-treatment- resistant depression. The majority of clinical studies on TRD have focused on pharmacotherapy- resistant depression, whereas relatively fewer studies have evaluated "next choice"
treatments for individuals who initially do not respond to
2.1.3. Current treatment modalities
Complete remission is defined as achieving 70-90% recovery of patients with depression which can measured by commonly used rating scales, such as the HAM- D (Al-Harbi, 2012; Rybak et al., 2021). Hence, 10%-30% refractory to treatment requires further management by various therapeutic modalities. According to the finding from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study conducted by the National Institute of Health, 50-66% of patients with depression do not recover fully on antidepressant therapies (Gaynes et al., 2009). In general, despite the effectiveness of the antidepressant medication, it is accepted that 1 out of 3 patients fail to achieve remission (Voineskos et al., 2020). According to a recent review (Voineskos et al., 2020), some most updated current treatment modalities of TRD are listed below:
Traditional Pharmacological Approaches: Augmentation, Lithium, Thyroid hormone (Triiodothyronine – T3), Second-generation antipsychotics.
Optimizing, combining, and switching classes of antidepressant pharmacotherapy: When a patient presents with a partial or nonexistent symptom response after an initial antidepressant trial, medication optimization is advised by both CANMAT and NICE guidelines for treating MDD. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are typically used as the first-line treatment for MDD. According to several studies, switching from SSRI/SNRI medications to older antidepressant classes has better results than doing
the same (Papakostas et al., 2008). Transitioning from SSRI/SNRI to tricyclic antidepressants (TCAs), particularly imipramine, has resulted in overall response rates of 44–73% (Simons & Thase, 1992). Tranylcypromine, phenelzine, and moclobemide are examples of drugs known as monoamine oxidase inhibitors (MAOIs). These are powerful antidepressants that are MAO-A and B enzyme inhibitors. Most studies looking at the effectiveness of switching to an MAOI were done by moving from a TCA, and they showed response rates of up to 60% (D.
Voineskos et al., 2020). Of note, literature consistently show the anti-suicidal effect of an antidepressant, lithium, and some mood stabilizers (i.e., valproate, lamotrigine, and carbamazepine) (Wasserman et al., 2020).
Psychotherapy: Despite the slower onset of action, a recent systematic review of 6 RCT studies indicates that psychotherapies added to standard care (with antidepressants) are beneficial in the short term for depressive symptoms, response and remission rates in patients with TRD (Ijaz et al., 2018). Some therapies were most recommended: dialectical behavioral, cognitive behavioral, interpersonal, and intensive short-term dynamic psychotherapy.
Brain stimulation: Several nonpharmacological treatments for TRD have been developed, including vagus nerve stimulation, electroconvulsive therapy (ECT), epidural cortical stimulation, and repetitive transcranial magnetic stimulation (rTMS) (including Conventional High-Frequency Left DLPFC rTMS, deep rTMS, Theta- Burst Stimulation, Accelerated rTMS Protocols), magnetic seizure therapy,
transcranial direct current stimulation, and deep brain stimulation (DBS) and some of them have shown promising outcomes (Wu et al., 2021).
Novel therapeutics: Ketamine: intravenous infusion, intranasal has demonstrated efficacy in combination with an oral antidepressant and has been authorized for restricted use in TRD by the FDA. In addition, a single infusion of ketamine reduced suicidal ideation in depressed patients with suicide ideation within one day to one week (Wilkinson et al., 2018). Psilocybin and Anti-inflammatories are also showed some evidence for efficacy in TRD treatment.
2.1.4. The burden of treatment-resistant depression
The impact and burden of TRD are immense and go far beyond their economic cost, which is often associated with increased suicidality and mortality (Demyttenaere
& Van Duppen, 2019). TRD patients are twice as likely to be hospitalized and are associated with 40% higher medical care costs among MDD patients (Gibson et al., 2010). According to a review of the clinical, economic, and societal burden of TRD in the US during 1996 – 2013, researchers estimated that at the rate of 12 – 20%
among all depressed patients, TRD may lead to an annual societal cost of 29 – 48 billion, and the substantial toll on patients’ quality of life (Mrazek et al., 2014).
Similarly, in Asian society, researchers in Taiwan and Japan also announced that the total healthcare cost of TRD patients leads to 61.8% compared to MDD without TRD (27.1%) (Klug et al., 2016; Ng et al., 2019). A retrospective observational study of
the humanistic and economic burden of TRD in five European countries, France, Germany, Italy, Spain, and the United Kingdom, revealed that TRD patients had significantly decreased quality of life, decreased work productivity, and activity impairment. It increased utilization of healthcare resources compared to non-TRD and the general population (Jaffe et al., 2019). Similarly, those with TRD had significantly higher all-cause healthcare resource utilization and costs than those with non-TRD MDD ($25,517 vs. $20,425, adjusted cost difference = $3,385) and non- MDD cohort ($25,517 vs. $14,542, adjusted cost difference = $4,015) among Medicare-insured patients in the United States between 2010 and 2016 (Pilon et al., 2019). This is consistent with the result in the systematic review of direct/indirect medical costs among TRD patients due to the need for additional treatment, which leads to the increasing use of medical resources, related costs, and work loss (Johnston et al., 2019). Significantly, the finding address the trend that medical costs increased and patient health-related quality of life decreased by increasing TRD/non- response within an MDD episode (Johnston et al., 2019).
2.2. Treatment-resistant depression and suicide risk factors 2.2.1 Concept of suicidality
According to WHO, in 2016, approximately 800.000 people died to suicide annually, which is one person completed suicide every 40 seconds. Third-fourth of these involves people from low- and middle-income countries (WHO, 2019). Asian
than the worldwide estimation (WHO, 2021). Despite the variation rate of suicide, the overall global age-standardized suicide rate was estimated at 10.5 per 100.000 population in 2016 (WHO, 2018). Three times as many men die by suicide as women in high-income countries, and the male-to-female ratio for suicide is more even in low- and middle-income countries, at 1.6 men to 1 woman (WHO, 2021).
Suicide can be defined as “intentional self-destruction resulting in your own death by your own action”. The various self-destructive behaviors and ideas following the assessment, explanation, treatment and control of suicide are diverse and complex (Maris, 2019). Figure 1 illustrates that the various self-destructive ideas and behaviors exist on a continuum, from totally non-suicidal thoughts/behaviors to completed suicide. Therefore, the term “suicidality” in this study was defined as any suicidal behavior, including suicidal ideation and suicide attempt.
It is estimated that for each person who dies by suicide, more than 20 others attempt suicide (CDC, 2018). Suicide and suicide attempts affect not only the families, friends, and workplaces of those who died but also people who still survive.
Nevertheless, the economic costs, social costs, and spiritual costs that one committing suicide, attack the whole community and its nation (Cutcliffe & Stevenson, 2008).
An estimated $93.5 billion have been paid by suicide and suicide attempts in combination with medical costs, direct and indirect costs as lost of productivity in families and individuals in 2013 in US (Shepard, Gurewich, Lwin, Reed Jr, &
Silverman, 2016). Finally, according to a cost-effective report (Shepard et al., 2016), every $1.00 spent on psychotherapeutic interventions that strengthened linkages
among different care providers saved $2.50 in the cost of suicides would lower overall suicides by 10%.
Figure 1. A continuum of suicidality
2.2.2. Treatment-resistant depression and suicide risk factors
2.2.2.1. Depression and history of suicide ideation and suicide attempt
In general, it is believed that more than 90% of those who commit suicides have been linked to a mental disorder despite the fact that the variation of higher rates in Western countries (90% - 95%) compared to Asian countries (63% - 97%) (Windfuhr et al., 2016). MDD has shown the strongest correlation between suicide ideation and suicide attempt; the prevalence of suicide attempts is highest among those with MDD (Omary, 2021). Recent US national data shows the increasing rate
of MDD and those with severe impairment were consistent with the number of deaths by suicide over twelve years (Hedegaard et al., 2020). In Vietnam, 67.6% (N = 309) of suicide attempters who were admitted to the Poison Control Center in Bach Mai Hospital, got confirmation of at least one mental disorder as the criteria of ICD-10, in which depressive disorder had the highest prevalence with 23.3% (Tuan et al., 2009). Overall, up to 80% of suicide cases reported to have a diagnosis of MDD in developed countries, but the prevalence in developing countries existed only half with approximately 45% (Windfuhr et al., 2016). This lower prevalence in developing countries reflects the robust evidence of stigmatization toward those with mental illness and restricted the use of mental health services.
The suicide process is complex with bio-psycho-social interactions (Lennon, 2019). Numerous risk factors for completed suicide have been recognized; however, having a history of suicide ideation and suicide attempt are considered the strongest indicators of subsequent attempts or completed suicide (Cooper et al., 2005).
Furthermore, history of suicide attempts is associated with a higher risk for completed suicide than having a mental disorder and up to 66 times greater risk than the general population (Hawton et al., 2003).
For those with TRD, having a previous attempt and comorbid psychiatric disorders were the strongest risk factors for suicide attempts (Reutfors et al., 2019).
Recent cohort studies in the US and Sweden population showed that patients with TRD had 29 to 35% higher all-cause mortality compared with non-TRD patients (those with treated MDD but without criteria for TRD) respectively (Li et al., 2019;
Reutfors et al., 2018). Similarly, researchers identified the prevalence of suicide ideation among patients with TRD as two-fold higher than in the non-TRD group (Dena et al., 2019). A recent finding from European multicenter identified 46.7% of 1410 MDD revealed suicidality and mild/moderate suicidality is significant associated with treatment nonresponse and resistance (Dold et al., 2018).
2.2.2.2 Suicide and the need of follow-up care by mental health services
A recent study in the United States further showed that inpatients with depressive disorders were the most hazardous group of completed suicide within 90 days of discharge compared to other psychiatric inpatients with diagnoses of bipolar, schizophrenia, substance use disorder, or other mental disorders, which were substantially higher 16.6 times than the general population (Olfson et al., 2016).
Further, two sharp peaks of suicide risk were demonstrated in the first week of admission and another in the first week after hospital discharge among patients with mood disorders (Qin & Nordentoft, 2005). Similarly, consistent with risk models that emphasize connectedness to health care professionals and other support, psychiatric inpatients were more likely to increase the short-term risk for suicide if they had not received any outpatient health care in the six months before hospital admission (Olfson et al., 2016).
There is still a misconception that because most suicides do not occur in hospitals, healthcare providers do not have a responsibility to assume the primary role
in suicide prevention (Grumet et al., 2019). It's interesting to note that according to Vietnamese researchers, the percentage of suicide deaths that occurred primarily at home ranged from 57 to 85%, with only 4.4% occurring in psychiatric hospitals (Dang, 2010; Huy, 2013). Additionally, during the follow-up period, roughly 12.5%
of the patients (31 per 100.000 person-year) attempted suicide again, which was three times the rate in the local general population (10.2 per 100.000 person-year) (Nguyen et al., 2010).
The reality, however, is very different: 83% of people who die by suicide have visited a doctor in the year prior to their passing, and almost 50% of suicide fatalities occur within a month of a primary care visit (Ahmedani et al., 2014). Additionally, approximately 40% of those who committed suicide attended the emergency room in the year before they died but did not get a mental health diagnosis. The majority of healthcare providers never inquire about a patient's risk, most healthcare systems are unprepared to care for people at risk, and most at-risk patients frequently go unnoticed, even though they have the opportunity to identify, treat, and save people from suicide (Grumet et al., 2019). Based on current knowledge, these care gaps are unwarranted and frequently fatal.
The post-discharge suicide rate was discovered to be approximately 100 times the global suicide rate during the first three months after discharge, and patients who admitted with suicidal thoughts or behaviors had double rates with close to 200 times the global suicide rate, according to a systematic review and meta-analysis of 100 studies with 183 patients (Chung et al., 2017). Notably, the meta-analysis results
revealed that 0.28 percent of all discharged patients could expect to die by suicide within the first three months after discharge. Moreover, even years after discharge, patients who had previously hospitalized for mental illness had suicide rates that were 30 times higher than those worldwide.
Therefore, the need of assessment and following up patients with high risk of suicide during hospitalization and short-term after discharge is a critical strategy for suicide prevention.
2.2.2.3. Psychological distress
Psychological distress generally includes anxiety, depression, hostility, insomnia, or anger, which varies depending on personal traits and culture. In addition, low levels of resilience and high distress tolerance significantly associated with depression (Huong et al., 2022; Liu et al., 2020). Researchers found that the multivariate-adjusted HRs (95% confidence interval) for completed suicide were 2.37 (1.49-3.78) among participants with moderate psychological distress and 4.16 (2.13- 8.15) among those with severe psychological distress, according to a recent publication based on a 7-year analysis of the Japanese national database. Participants with moderate psychological distress had a population-attributable suicide rate (26.8%) that was approximately 2.5 times higher than those with severe psychological distress (10.0%) (Tanji et al., 2018). Further, compared to the general
population, psychiatric patients appeared more severely in psychological distress, about 4.6 to 6.7-fold (Wu et al., 2016).
A longitudinal population-based study of a large sample of suicide attempters registered in the Taiwanese national suicide surveillance system revealed that psychological distress level significantly predicted the risk for eventual suicide within one year (Wu et al., 2020). Furthermore, this study demonstrated that psychological distress was a significant and long-lasting predictor of subsequent suicide attempts within a year of the initial attempt. These findings provide solid evidence that suicide is not only a problem of acute crisis, but also a chronic issue of persistent psychological distress that varies over time. (Maris, 2019), so that suicide assessment needs to be repeated and applied for the individual with high risk in short-term and long-term follow-up (Boudreaux & Horowitz, 2014).
2.2.2.4. Hopelessness
Those experiencing hopelessness have a pessimistic attitude about the future and a lack of coping skills to stressors, and hopelessness acts as a mediator between psychological distress and suicide ideation (Alsalman & Alansari, 2016; Lew et al., 2019; Miranda et al., 2013). Hopelessness is among the most cognitive risk factors for suicidal ideation, suicide attempt, and suicide intent among inpatients and outpatients with MDD (Beck et al., 1990; McCullumsmith et al., 2014; Wang et al., 2015). The result from a meta-analysis revealed that the strongest predictor for suicide
ideation was hopelessness, followed by depressive symptom and a MDD diagnosis (Ribeiro et al., 2018). Hopelessness was a significantly stronger predictor than depression for suicide risk (Zhang & Li, 2013). Some studies examined the relationship between hopelessness, depression, and suicide ideation and demonstrated that hopelessness was the only significant predictor of depressive symptoms and suicide attempts (Horwitz et al., 2017; Wolfe et al., 2019). Therefore, there is a need to examine the role of hopelessness among patients with TRD in clinical and community settings. However, to reduce the burden on participants and encourage a high response rate (Fraser et al., 2014), we decided to use a brief measure with one questionnaire to assess the hopelessness level of patients with TRD.
2.2.2.5. Quality of life
Quality of life (QoL) measurement has been applied in research and clinical settings for patients with TRD as an indicator for measuring the successful treatment in which depression severity may contribute to reduced patient health-related quality of life and health status (Jamieson et al., 2020; Johnston et al., 2019). A recent study in the US, which applied the World Health Organization Quality of Life scale (WHOQOL-BREF) to measure QoL in people with TRD, demonstrated that QoL scores are lowest in the physical and psychological domains (Lex et al., 2019). In addition, QoL found modestly correlated with depressive symptoms, which were recorded by the patients, self-rated, and even lower with clinician-rated. This result
In order to develop novel biological, psychological, and social interventions when caring for a patient with TRD, QoL should be assessed and targeted as a distinct clinical outcome (Lex et al., 2019). A multi-nation study across five European countries showed that TRD had the poorer worse health-related quality of life (HRQoL) defined by the EQ-5D-5L, EQ-VAS scores, and SF-12 version 2, compared with the non-TRD group and general population even after adjusting for potential confounders (Jaffe et al., 2019). Research on the correlation between the quality of life and suicide has shown robust evidence that good quality of life has a significant positive correlation with depression and suicidal ideation (Lee et al., 2019; Ponte et al., 2014).
2.3. Miscellaneous risk/protective factors for suicide in the community 2.3.1. Community integration
2.3.1.1. Concept of community integration
A recent review states that community recovery refers to the multi- dimensional process in the community where people with mental illness are integrated (Halperin, 2018). According to Davidson and Roe (Davidson & Roe, 2007), recovery is considered when a person could have a meaningful life while continuing to have a mental illness. Many authors have gradually expanded the definition of community integration over the years, but most include three domains widely viewed as integral to the concept: productivity, social activity, and independent living (Migliorini et al., 2016). Productivity may involve employment,
volunteer work, or educational pursuits, thereby providing a meaningful role in the community. Love and friendships, community ties, a sense of belonging, and being part of a network are what social activity is all about. Lastly, independent living refers to having a home that you are responsible for and is a significant indicator of adulthood. Recent studies supported the importance of social relationships as a critical influence on community integration outcomes related to the quality of life (Callaway et al., 2016; Parvaneh & Cocks, 2012). In addition, social network communication has been recognized as increasing social integration and reducing loneliness which needs to be measured together with community integration to provide further direction for occupational therapy practice (Callaway et al., 2014, 2016).
2.3.1.2. Community integration in the depression trajectory
Community integration is an important concept that affects individual recovery for depressive patients (Bennabi et al., 2015; Wu et al., 2016). A recent review suggests that delaying the treatment of MDD can cause progressive damage to brain regions associated with depression, and that pharmacotherapy can reverse these effects, highlighting the importance of treating depression as soon as possible to achieve full recovery (Oluboka et al., 2018). In addition, researchers have addressed the key domains that affected the level of community integration among individuals with MDD, including home and family life, productivity, and social activities (Wu et al., 2016). A qualitative study in Iran showed that the biomedical
model was insufficient for patients with MDD who attained higher levels of health and functionality than their depression status (Amini et al., 2019). It is a fact that patients with TRD struggle in many performances related to their social roles during recovery.
Despite the challenge of the long-term effects of functional impairment, high recurrence, and high suicidal risk (Bennabi et al., 2015), there are relatively few scales to assess community integration level, which is an essential concept in the recovery model. In this context, researchers have addressed the key domains, including home and family life, productivity, and social activities, which affected the individual level of community integration among patients with major depression (Wu et al., 2016) or TRD (Huong et al., 2022). A review of 51 studies illustrated related predictors to nonresponse antidepressant treatment, such as age, longer duration of depressive episodes, moderate to high suicidal risk, comorbidity, personality disorders, frequent hospitalization, and marital status (De Carlo et al., 2016). As a result, it implicitly indicated that the outcome of TRD treatment needs more instruments to explore in detail the patients' daily living problems and social support. A recent study in Korea has carried out this concept in the application of the Self-Reporting Scale of Community Integration (Korean version) to explore patients with severe mental illness in five dimensions: psychological integration, physical integration, social support, social integration, and independence (Jun & Choi, 2019). However, the instrument still cannot indicate the reintegration progress for a person with TRD in its entity. In addition, the need to assess functional impairment and quality of life has been addressed in a recent study (Gaynes, 2020). Hence, the literature pointed out the
use of Community Integration Questionnaire-Revised (CIQ-R) (Callaway et al., 2014) that evaluates the integration level in terms of independent living situations, leisure activities, productivity, and electronic social networking in samples of individuals with neurological and neuropsychiatric disorders (Migliorini et al., 2016;
Tomaszewski & Mitrushina, 2016). From the literature review and to our knowledge, no study has specifically addressed the relationship between such community integration level and suicidality among patients with TRD in a longitudinal study. To disseminate a comprehensive cultural model to help patients return to the communities with better recovery and to facilitate a care model more productive, the community integration level needs to be examined in this target population.
2.3.2. Family support
Many studies show the negative effect of MDD on other family members as partners and children. Further, marital and family dysfunction is associated with prolonged depression, a higher relapse rate, and an increased risk for suicide (DiBenedetti et al., 2012). Generally, family support is one of the most important factors affecting how patients adapt to illness (Shor et al., 2013). A recent systematic review and meta-analysis of 14 studies provided more robust evidence about the strong association between family dysfunction and depression with OR of 3.72 (95%
CI, 2.70 to 5.12; I2 =24%) (Guerrero-Muñoz et al., 2021). Of note, the family functionality measured by the Family APGAR in 12/14 studies shows low heterogeneity in this analysis (Guerrero-Muñoz et al., 2021). Family support has been
proved in the body of literature as the protective and moderator effect between depression and suicide ideation and is vital in supporting suicide prevention (Edwards et al., 2021).
In Vietnamese culture, little knowledge about the relationship between family functionality, especially among those living with TRD. Therefore, it is helpful for healthcare providers to assess the impact of depression on family functioning to provide a more comprehensive evaluation of treatment for MDD, especially TRD.
Therefore, in this study researcher will use the Family APGAR to assess the family function of all the participants to understand family support among TRD patients.
2.3.3. Resilience
Resilience is the ability to rise above difficult situations (Criss et al., 2002) and the innate human capacity to deal with significant challenges (PeConga et al., 2020). According to the Protective Factor Model of Resilience, resilience can play a moderating role by interacting with risk factors in order to mitigate the negative effects on the outcome (Johnson et al., 2011). Studies conducted over the past decade indicate the protective effect of resilience in reducing the negative impact of suicide risk factors, suggesting that positive psychological interventions for resilience building may be effective in suicide prevention (Yang et al., 2021). A study conducted across three age cohorts (28-32, 48-52, 68-72) showed low resilience was associated with an increased risk for suicidality (Liu et al., 2014). Therefore, there is
strong evidence that resilience training should be incorporated into universal, selective, and indicated suicide prevention interventions (Sher, 2019).
2.4. Current development of depression and suicide care in Vietnam 2.4.1. Introduction of the general health care service
Vietnam has a population of 97.957.634 – the 15th highest population in the world (Vietnamese population, 2021). Vietnam has 330.991 square kilometers with long borders with China, Laos, and Cambodia and 3.444km of coastline. Among 54 ethnic groups, Kinh is the largest group, with approximately two-third of the population are living in rural areas, and a fourth-fifth of the population speaking the Kinh language – official Vietnamese. The adult literacy rate is 95%, and per capital income is USD 3.498 (World Bank, 2021). The life expectancy at birth has been increasing in recent years, with 69 for males and 78 for females (WHO, 2021).
The Vietnamese government has spent 7.7% of its GDP on higher healthcare services compared to some neighboring Southeast Asia countries (WHO, 2021). Up to 87% of the Vietnamese population was covered by social health insurance in 2018, which the poor, ethnic minorities, under six children and elderly above 80, and socially vulnerable group are fully covered by full government subsidy for premium (WHO, 2018). However, despite increasing health insurance coverage, extra payments also increase for which the health insurance does not fully cover the expenses of the health-care providers (Nguyen et al., 2019).
The national, province, district, and commune services are the four tiers of the Vietnamese administrative health system. In certain isolated areas, commune health clinics are in charge of a network of village health professionals.
2.4.2. Mental health care system in Vietnam
Currently, there are 45 psychiatric hospitals and 19 psychiatric departments in provincial general hospitals with total of 9059 beds (9.43/100.000 population).
There are 1074 psychiatrists, 2882 psychiatric nurses, 117 psychologists, and very few occupational therapists and social workers, with only 3 and 15, respectively (National Psychiatric no 1, 2021). The Ministry of Health and the Ministry of Labor, Invalids, and Social Affairs are responsible for the treatment and collaboration in the care and follow-up of patients with chronic mental illnesses. In addition, most provinces have mental hospitals or Prevention and Control Centers for Social Diseases to treat social diseases and take care of chronic mental patients. The mental health service in Vietnam can see in detail in Figure 2 (Cuong, 2017).
Vietnamese mental health care system focuses mostly on the provincial and national level which provides a very limited quantity, and care services to follow-up patients in the community (Vuong et al., 2011). Community mental health networks in Vietnam focused mostly on screening, prescription, and follow-up monthly for medication only that covers patients with schizophrenia and chronic epilepsy since 1999 (Cuong, 2017). On the other hand, anxiety, depression, and attention-deficit/
hyperactivity disorder have got attention since 2015 but face a lot of difficulties, such
as lacking staff and mental health background experience in primary healthcare (Cuong, 2017). This may explain the fact higher number of depressive inpatients than in developed countries.
In addition, there are limited mental health community facilities and government resources for mental health care networks. Researchers have shown limitations of the Vietnamese mental health care system including a lack of mental health policy and legislation; inappropriate service organization and planning; a shortage of human resources; and a lack of evidence-based interventions (Nguyen et al., 2019). In addition, there is still a substantial gap between treatment needs and accessibility for mental disorders, which is exacerbated by stigmatization-related treatment and assistance-seeking barriers (Van der Ham et al., 2011).
2.4.3. Epidemiology of depression and suicide prevention in Vietnam
According to Vietnamese national data source, the prevalence of mental health disorders is 14.2%, with 5.3% alcohol addiction, 2.45% depression disorder, and 2.6% anxiety depression being the three most prevalent (National Psychiatric hospital no 1, 2014). Vietnamese crude suicide rate was 7.3 per 100.000 population (about 6868 people) with a ratio of male to female 2.95:1 (WHO, 2019). The most common methods were pesticide poisoning and hanging, with 50-60% suffering from depression and anxiety (Nguyen et al., 2010; Tuan et al., 2009; WHO, 2014).
According to WHO, every country should promote and set up a national suicide prevention program with the promotion slogan “suicide prevention is
everyone business” (WHO, 2018). Unfortunately, national strategies for the prevention of suicide in Vietnam have not yet been developed. As a patient safety goal, the suicide death rate among hospital inpatients has been added to the national hospital accreditation standards of the United States, which require hospitals to conduct risk assessments for patients at risk of committing suicide (The Joint Commission, 2014). However, it has not been recognized in the latest Vietnamese national hospital accreditation standards in 2016 (Vietnam Ministry of Health, 2016).
The Joint Commission issued Sentinel Event Alert urging “all healthcare organizations providing both inpatient and outpatient care to better identify and treat individuals with suicidal ideation” (Grumet et al., 2019). These developments indicate that enhanced opportunities for suicide care are becoming explicit compliance requirements, and healthcare systems should be prepared to adapt to these requirements (Grumet et al., 2019).
Figure 2. The mental health services in Vietnam
(Tran Van Cuong, 2017)
