1 INTRODUCTION Major depressive disorder (MDD) occurs from to 10 percents at primary health care and approximately 50 percents of MDD and dysphoric disorders weren’t detected on examination Studies pointed out that the majority of depressed patients didn’t receive appropriate treatments Treatment for dpression current is composed of drug therapy, biological therapy, and psychotherapy International researchers, through clinical trials, stated that behavioral therapy (BA) is effective in reducing and suppress depressive symptoms (Kanter, 2010; Ritschel, 2011) Studies showed that BA is simple, teachable, learnable, doesn’t require that therapists need to have complex skills, easier to accept for population than with medicines, effective interms of time and cost, designed favourably for following up patients and for therapists, and easy to generalize in the community In Vietnam, at primary health care level, treatment for depression is mainly medicines while effective BA for depression hasn’t been applied in the community yet The research “Assessing the effectiveness of treating major depressive disorder by combining behavioral therapy with amitriptyline at communes/wards of Khanh Hoa province” will illustrate the benefits of BA, with two objectives: Describe MDD patients features at communes/wards of Khanh Hoa province in 2011 Assessing the effectiveness of treating major depressive disorder by combining behavioral therapy with amitriptyline at communes/wards of Khanh Hoa province from 2012-2015 New contributions of the dissertation - Provide description on MDD in the community at four communes/ wards of Khanh Hoa province, through which, provide to policy makers prevention and management stratergies for currently increasing MDD - Initially assess the effectivenes of BA combined with amitriptyline at communes/wards of Khanh Hoa province Struture of the dissertation The dissertation is composed of 144 pages of main contents, 37 tables, figures, 160 references, 10 appendices (patient’s chart sample, patients list, research tools) 2 Chapter OVERVIEW 1.1 Overview on depression 1.1.1 Concept of depression Depression is pathologic status of emotion, manifesting by an inhibited process of all the areas of mental activities (emotion, thought, activities…) According to the 10th Internation Classification of Diseases, depression manifests by three characteristic symptoms: depressed mood, loss of interest and enjoyment, reduced energy leading to increased fatiguability and diminished activitiy; seven other common symptoms: reduced concentration and attention, reduced self-esteem and self-confidence, idea of guilt and unworthiness, pessimistic views of the future, ideas or acts of self-harm or suicide, disturbed sleep, diminished appetite The symptoms exist in at least two weeks 1.1.2 Aetiology of depression Depression is due to multiple causes, but in general there are three main causes: psychologic, organic, and endogenous 1.1.3 Mechanism of depression Neurotransmitters an receptors play important roles in depression Central neurotransmitters biogenic amines (serotonin (5HT), epinephrine, norepinephrine (NE), dopamine (DA), acetylcholine, histamine), amino acids (glutamate, gama aminobutiric acid - GABA), and peptides Depression is associated with the abnormal functions of neurotransmitters, in which, the most important are 5HT, NE, DA, and related receptors; and even the changes in the forms and functions of the brain 1.1.4 Diagnosis and classification of depression according to ICD-10 1.1.4.1 Diagnostic criteria of depression according to ICD-10 - Three characteristic symptoms: depressed mood, loss of interest and enjoyment, reduced energy leading to increased fatiguability and diminished activitiy 3 - Seven other common symptoms: reduced concentration and attention, reduced self-esteem and self-confidence, idea of guilt and unworthiness, pessimistic views of the future, ideas or acts of self-harm or suicide, disturbed sleep, diminished appetite - Somatic symptoms of depression: loss of interest or pleasure in activities that are normally enjoyable; lack of emotional reactivity to normally pleasurable surroundings and events; waking in the morning hours or more before the usual time; depression worse in the morning; psychomotor retardation or agitation; marked loss of appetite; weight loss (often defined as 5% or more of body weight in the past month); marked loss of libido - Psychotic symptoms such as delusion, hallucination maybe present or not present in depressed episode - Determination of the severity of depression (mild, moderate, severe) bases on the numbers of characteristic and common symptoms of depression of patients; the impacts on scopes of social and occupational activities of patients; the presence of psychotic symptoms; and the duration of depression episode 1.1.4.2 Classification of depression Depresion has types: endogenous, psychologic, and organic 1.2 BA in depression treatment 1.2.1 Definition of BA According to Martel (2010), BA is brief, structured therapy aimed at activating patients by special ways in order to increasing reward experiences for their lifes; an independent therapy and an important component of cognitive behavioral therapy in treating depression According to Dimidjian (2011), BA is a brief, strutured psychotherapy aimed at (a) increasing the engagement in appropriate activities (usually related to pleasure or mastery experience), (b) decreasing engagement in activities that maintain depression or increase depression risk, and (c) dealing with problems limiting access to reward, or maintaining, or increasing the control of aversive feelings BA will focus directly on those objectives 1.2.2 Mechanism of BA According to Martell, the techniques of BA increase the activation, decrease the avoidance, increase the contact with positive reinforcement for non-depressive behaviors, and mood increasing behaviors By the time, this process will lead to decreasing depression symptoms BA activates patients contacting with positive reinforcers, scheduling to participate in pleasurable events BA helps patients engaging more on pleasure activities, provides a clear assessment on patients’ purpose and present behavioral function in order to determine the activated objectives to focus on BA also trains patients social skills and how to analyse their behavioral function themselves; encourages the assessment of negative reinforcers for avoidance behaviors of depression đánh giá củng cố tiêu cực cho hành vi né tránh trầm cảm As a result, BA activates behaviors decreasing, supressing symptoms, dosen’t imoact on the causes as well as mechanism of depression 1.2.3 Objectives of BA Decrease the slowness, lack of activity of depressed patients; decrease avoidance behaviors, activate activities to improve emotion; decrease negative activities 5 Chapter STUDY SUBJECTS AND METHODS 2.1 Study subjects 2.1.1 Selection criteria - Patients from 18 to 65 years old, diagnose of MDD by psychiatrists following ICD-10, capable of reading, writing, and hearing Vietnamese - Patients voluntarily agree participating in the study 2.1.2 Exclusion criteria Patients having cognitive impairment, psychotic, manic symptoms, substance abuse, severe medical illnesses, contraindications with amitriptyline 2.2 Locations and period of time of the study Two Phuoc Tan, Phuoc Hoa wards of Nha Trang city, and two Dien Son, Dien Phu communes of Dien Khanh distrist of Khanh Hoa province, from October of 2012 to October of 2015 2.3 Study methods 2.3.1 Study design Non-randomized, controled community intervention study Prospective study with follow-up for six months 2.3.2 Sample size WHO formula: {Z n1 = n2 = 1− α 2 P (1 − P − ) + Z1−β p1 (1 − p1 ) + (1 − p2 ) } ( p1 − p2 ) in which: n1: Minimum sample size of controlled group, n 2: minimum sample size of intervention group p1: Rate of remission patients expected in the controlled group = 50%, p2: Rate of remission patients expected in the intervention group = 85% P = (p1 + p2)/2 Z(1- α /2): Reliability at 95% level (= 1,96) 1-β: Sample power (= 80%) The minimum sample size for each group n1 = n2 = 30 patients Due to the fact that intervention for depression having high rate of dropout we have to recruit n1= 62 and n2 = 64 to make sure that we have at least 30 patients to follow-up until the end of study which is the week of 30 (T30) 2.3.3 Patients follow-up plan - Intervetion group: after finishing treatment (6 weeks), patient will be re-examined and given amitriptyline every two weeks, continuously for 30 weeks - Controlled group: after finishing treatment (6 weeks), patient will be re-examined and given amitriptyline every two weeks, continuously for 30 weeks * All the important steps, such as screening at households, interview by PHQ-9, conducting BA sessions, are implemented by the study group members who were carefully trained 2.3.4 Tools used in the study - PHQ-9 (Appendix 5) – rate the severity of depression and monitor treatment response Define mild degree when PHQ-9 score from 10-14, moderate from 15-19, and severe from 20-27 - BADS-SF (Appendix 7) – assess behavioral change of depressed patients after treatment by BA All the questions of BADS-SF can be answered by levels as following: – not at all, – very little, – a little, - moderate, – a lot, – very much, - completely The higher of BADS-SF is the higher of behavioral activation level BADS-SF score negatively correlate with depression severity, avoidance behavior, automatic depressed thoughts; positively correlate with reinforce possibility, quality of life, active adapatation - Other questions to collect information about related factors: demography, social-economic conditions…(Appendix 7) 7 - Assess the effectiveness of treatment on depression degree The study assess the effectiveness of treatment on depression degree bases on the changes of PHQ-9 score The more decrease the PHQ-9 score is the more effectiveness the treatment is, and vice versa - Assess the effectiveness of treatment on depression behavior: bases on the changes of BADS-SF score The more increase the BADS-SF score is the more increase the level of activation behavior is, and vice versa - Assess the effectiveness of treatment on remission, recovery, relapse, recurrence, bases on PHQ-9 score - Remission – a short period of time having no depression symptoms: PHQ-9 < since the point of T6 on - Recovery – a period of remission lasting at least months: PHQ-9 < at the point of T30 - Relapse – the return of depressed symptoms, occuring in the remission period, before recovery period: PHQ-9 > again among months after having had PHQ-9 2.4 Data entry and analysis Data were entered and analyzed using EpiData 3.1 and STATA 12.0 8 Chapter STUDY RESULTS 3.1 Individual characteristics of study subjects Table 3.1 Individual characteristics of study subjects Individual factors Age Gender Education Marriage Occupation 18 -