9

Depression

DEFINITION

The term “depression” can apply to a transient mood, a sustained change in mood, a symptom, or a disorder. In this chapter, the term is used to refer to unipolar/major depression that is characterized by persistent low mood or sadness and accompanied by both physical and psychological symptoms of at least 2 weeks duration and with associated impact on social functioning. Both genetic and environmental factors are implicated in the etiology of depression.[1,2 and 3]

Depression can present as acute episodes with depressive psychosis that are severely disabling yet often treatable, and when recurrent are controllable with maintenance pharmacotherapy. More often depression presents as an overlapping syndrome of depression, anxiety, and somatization forms such as bodily aches and pain, persistent backache, or genitourinary complaints.

The diagnosis of a depressive illness is based on symptomatology, the severity and duration of the symptoms, and their impact on social functioning. Cases may be identified by means of self-rating on a questionnaire or observer assessment. In the latter case, the patient is interviewed by a health professional with training in assessment and diagnosis (the level of training being consistent with the local resources available for mental health services). The use of operational criteria strengthens the reliability of a conventional clinical interview. Operational diagnosis of psychiatric disorders, which seeks to identify patterns of symptoms that characterize a given illness most reliably, has been one of the major advances in psychiatry within the last 40 years. This diagnostic method allows clinicians to classify illnesses even when etiology is unknown, and hence to communicate about and conduct research on patients with similar characteristics.[4,5 and 6]



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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World 9 Depression DEFINITION The term “depression” can apply to a transient mood, a sustained change in mood, a symptom, or a disorder. In this chapter, the term is used to refer to unipolar/major depression that is characterized by persistent low mood or sadness and accompanied by both physical and psychological symptoms of at least 2 weeks duration and with associated impact on social functioning. Both genetic and environmental factors are implicated in the etiology of depression.[1,2 and 3] Depression can present as acute episodes with depressive psychosis that are severely disabling yet often treatable, and when recurrent are controllable with maintenance pharmacotherapy. More often depression presents as an overlapping syndrome of depression, anxiety, and somatization forms such as bodily aches and pain, persistent backache, or genitourinary complaints. The diagnosis of a depressive illness is based on symptomatology, the severity and duration of the symptoms, and their impact on social functioning. Cases may be identified by means of self-rating on a questionnaire or observer assessment. In the latter case, the patient is interviewed by a health professional with training in assessment and diagnosis (the level of training being consistent with the local resources available for mental health services). The use of operational criteria strengthens the reliability of a conventional clinical interview. Operational diagnosis of psychiatric disorders, which seeks to identify patterns of symptoms that characterize a given illness most reliably, has been one of the major advances in psychiatry within the last 40 years. This diagnostic method allows clinicians to classify illnesses even when etiology is unknown, and hence to communicate about and conduct research on patients with similar characteristics.[4,5 and 6]

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World While criteria for diagnosis have been standardized by the American Psychiatric Association [7] and the International Classification of Disease, 10th revision,[8] their criteria are often of limited applicability in non-psychiatric settings, especially by primary care physicians, who often see patients with significant physical comorbidity. The accurate and timely diagnosis of depression is also complicated by the reluctance of patients to seek help because of the stigma associated with mental illness and by the nature of the complaints, which may often be thought to have a physical origin.[9] There have been continuing studies on the reliability and validity of various methods of assessing depression, and in parallel there has been continuing work on evolving the classification systems and criteria used for these disorders. Current standardized classification systems used for depression appear in Table 9-1 and Table 9-2. TABLE 9-1 DSM-IV Criteria for Major Depressive Episode Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning: at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by others; Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day; Significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day; Insomnia or hypersomnia nearly every day; Psychomotor agitation or retardation nearly every day; Fatigue or loss of energy nearly every day; Feelings of worthlessness or excessive or inappropriate guilt nearly every day; Diminished ability to think or concentrate, or indecisiveness, nearly every day; Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. The symptoms do not meet criteria for a Mixed Episode (see Table F). The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The symptoms are not due to the direct physiological effects of a substance or a general medical condition. The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation. Source: [7]

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World TABLE 9-2 ICD–10 Criteria for depressive episode General Episode must have lasted at least two weeks with symptoms nearly every day Change from normal functioning Key symptoms (n = 3) Depressed mood Anhedonia Fatigue/loss of energy Ancillary symptoms Weight and appetite change Sleep disturbance Subjective or objective agitation/retardation Low self esteem/confidence Self reproach/guilt Impaired thinking/concentration Suicidal thoughts Criteria Mild episode: 2 key, 4 symptoms in total Moderate episode: 2 key, 6 symptoms in total Severe episode: 3 key, 8 symptoms in total Exclusions No history ever of manic symptoms Not substance related Not organic Source: [8] The vast majority of research on the clinical features of depression has been conducted in the United States and Europe. Although far fewer in number, comparable studies from the developing world deserve careful attention, for they reveal significant differences in the presentation of depression among cultures, as well as core features common to all societies. Where possible in this chapter, we examine and compare findings from research in both developed and developing countries. For the purposes of comprehensive reporting, developed-country data are noted and used alone when findings from developing countries are not available. Although symptoms of depression are found everywhere, the Western bio-medical definition of depressive illness does not fit local concepts of illness in many developing communities.[10,11] Diagnoses of some mental disorders, including depression, have no conceptual equivalent in many languages. In non-European cultures, for example, use of the term “depression” often leads to the mistaken belief that sadness is an essential presenting feature of the disorder. While the experience of dysphoric mood may be universal, the concept of depressive disorder that focuses on mood must be recognized as having evolved within Western cultures, and therefore may not be universally applicable.[12]

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Several authors also imply that Cartesian mind–body dichotomies are absent from certain cultural worldviews. Nichter (1982), for example, noted that South Havik Brahmin women express distressed emotions and other social problems in terms of dietary preference for certain foods, religious metaphors, or humoral imbalance in the body.[13] Chinese popular explanations of mental illness ascribe problems to an imbalance in the psychosocial, physiological, or supernatural environment.[14,15] In African societies, health is viewed as more social than biological, and a unitary concept of psychosomatic interrelationship exists, with an apparent reciprocity between mind and matter.[16] Because these conceptualizations strongly influence how people express the experience of psychological distress and dysphoric mood, standardized instruments may not be applied accurately without regard to cultural differences among populations. Nevertheless, studies show that depression is found in countries around the world with significantly different cultural traditions and levels of economic development.[17,18 and 19] The majority of people with depression eventually consult primary care doctors or nurses. While the overall symptoms of depression are ubiquitous in population surveys, research has shown somatic symptoms to be the most common presenting features of depression in developed as well as developing societies.[20,21 and 22] Most commonly, patients present with physical symptoms such as lack of energy or vitality, fatigue, and aches and pains.[20,23,24 and 25] Several studies in developing countries indicate that when people with depression present with somatic symptoms, they will upon questioning also report that they have experienced classic psychological symptoms of depression.[20,26,27] SCOPE OF THE PROBLEM Depressive disorders are common around the world and are associated with significant disability.[18,28,29,30 and 31] Depression is a long-term illness that produces significant psychological, physical, and functional disability.[28,32,33 and 34]. In a study conducted in Malaysia, over half the patients with chronic depression had dysfunctional behavior and experienced significant disabilities.[35] Indeed, depression is estimated to be the leading cause of disability worldwide, accounting for more than 1 in 10 years of life lived with disability. Those suffering from depressive disorders also have high premature mortality, both from suicide and from physical illness.[ 17,18,35,36] Prevalence rates for depression vary among and between countries, but age of onset, social and environmental risk factors, and the preponderance of depressive disorders within families are similar across many cultures. Once recognized, depression can often be treated effectively. Though treatments are often not entirely curative, they offer significant relief from many of the debilitating symptoms of depression and can significantly improve the level of social functioning. Yet depressive disorders still remain largely underdiag-

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World nosed and untreated around the world. Even in developed nations, depressed patients consistently receive either no medication or dosages that are ineffective in treating their symptoms.[19,37,38] Mortality Suicide Suicide is estimated to be the 10th leading cause of death worldwide.[31] These estimates are based on nationally collected official data on suicide, which are thought to be significantly underestimated because of the stigma often associated with suicide. Reported rates of suicide vary widely throughout the world, with some of the highest rates being found in developing countries. For example, Sri Lanka [39] has the highest suicide rate in the world, followed closely by China.[40] Factors affecting the suicide rate among a given population include the rate of depression; the prevalence of alcohol abuse; the presence of high-risk occupational and demographic groups, including people with severe mental illness; the availability of easy means of suicide; the degree of social integration; and cultural attitudes toward suicide. Psychological autopsy studies (which gather detailed information about the deceased from multiple key informants) indicate that more than 90 percent of people who commit suicide suffer from depression, substance abuse, psychosis, or some other form of mental illness.[ 41,42 and 43] In a major review of all studies of suicide reported in the English literature, Harris and Barraclough (1998) found that people with affective disorders combined (major depression, bipolar disorder, and affective disorder not otherwise specified) were 20 times more likely to kill themselves than the general population.[44] In non-Western countries, however, completed suicides may be less likely to have received a psychiatric diagnosis because of the paucity of mental health services. Suicides often appear to be precipitated by a “last-straw phenomenon”: a recent social stress or life event in the context of multiple preexisting social stresses and an underlying mental illness. Official statistics tend to highlight the existence of social stresses rather than any underlying depression or other mental disorder. In settings where police officers, coroners, or physicians without mental health training are recording data about the principal causes of suicide, they are likely to focus on social and situational problems, rather than on preexisting depression. However, community surveys reveal that social problems are correlated with high rates of depression and anxiety.[45,46 and 47] Individuals with limited or dysfunctional social networks have been shown to be predisposed to depression, suicidal thoughts, and suicide.[ 48] Similarly, at the broader societal level, social disruption in contemporary industrialized society is believed to contribute to anomie, depression, and suicide.[49] The suicide rate in Sri Lanka rose from 6.5 per 100,000 in 1950 to 47 per 100,000 in 1991 following

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World a period of profound social upheaval and violence.[39] War and social disruption have been associated with dramatically different suicide rates in various settings. Access to means of suicide has a major influence on the suicide rate.[ 50] Where rapid and effective means of self-destruction are readily available, people making impulsive gestures may commit suicide inadvertently. This may explain at least in part the extremely high rates of self-poisoning with insecticides among young women in China, Sri Lanka, and Western Samoa.[39,40,51,52] Medicines that can be obtained without prescription and are lethal in overdose may also be used for self-poisoning. Barbiturates are frequently used in this way in Nigeria, as are chloroquine in East Africa [53] and paracetamol in Europe.[54] In addition, potentially lethal features of urban or rural landscapes appeal to those at risk by virtue of their symbolic association as an effective means of suicide. For example, tall buildings in Singapore and Hong Kong are popular sites for suicidal jumpers.[55] Physical Illness A growing body of evidence links untreated depression to severe and life-threatening physical illness.[56] Depression is associated with high premature mortality from physical causes, irrespective of premature mortality from suicide and trauma.[ 57,58 and 59] In a 40-year study, Ford and colleagues (1998) found that increased risk of coronary heart disease among people with major depression persisted for years after their first depressive episode. The increased risk was present even for myocardial infarctions occurring 10 years after the first depressive episode.[59] Examining data from the Baltimore, Maryland, site of the Epidemiological Catchment Area Study, Pratt and co-workers (1996) found a fivefold increase in the risk of myocardial infarction following major depression and a twofold increase in those who suffered from less severe (subsyndromal) depression. The increased risk of cardiovascular disease with depression appears to apply equally to men and women.[60,61 and 62] Conversely, high rates of depression have been found in older patients suffering from cerebrovascular disease.[63,64] The significant disability often associated with recovering stroke patients may account for episodes of depression.[63,65] A recent study has suggested that cerebrovascular disease may have an etiopathological role in late-life depression. The increased damage to frontal and subcortical brain circuitry following stroke, transient ischemia, and hypertension may explain the high prevalence of depression in older individuals with vascular risk factors.[66] Hormonal changes may go a long way toward explaining how depression results in physiological harm. For example, major depression leads to increased activation of the hypothalamic-pituitary-adrenal axis, which has in turn been associated with decreases in bone mineral density and increases in intra-

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World abdominal fat, a known risk factor for coronary artery disease.[ 67,68 and 69] Researchers have examined the link between depression and osteoporosis.[ 70,71] One such study reported that depression-associated loss of bone density could be expected to increase hip fractures by more than 40 percent in 10 years.[68] Social and Economic Costs The most comprehensive analysis to date of the worldwide impact of depression was performed in 1990 as part of the Global Burden of Disease (GBD) study. A major finding of this study, released in 1996, was that conditions such as mental disorders that disable, may cause less mortality than a number of physical conditions, but exact a high cost in disability throughout the world. Previous public health assessments, derived only from mortality data, did not rank mental disorders among the most burdensome diseases. Once disability was entered into the equation, mental disorders joined the ranks of cardiovascular and respiratory diseases, revealing a burden that surpassed both AIDS and all combined malignancies.[31] The disability-adjusted life years (DALYs) methodology employed in the GBD (see Appendix B) provides a way of linking information on disease occurrence to information on short- and long-term outcomes, including disabilities and restrictions on participation in usual life situations. The disability component is weighted according to the severity of the disability. For example, in the original GBD study, disability caused by major depression was weighted as being equivalent to blindness or paraplegia. Thus calculated, the GBD study ranked depressive disorders (considered as a single diagnostic category) as the leading cause of disability worldwide. The GBD study also resulted in the prediction that in 2020, as the result of a combination of several demographic and epidemiological trends, unipolar major depression will rank second only to ischemic heart disease as the leading cause of disease and injury worldwide. These trends include the breakdown of extended family networks; increasing urbanization, migration, and mobility; and alcohol and drug abuse. In addition, the expected growth of the world's population, overall increases in life expectancy, and relative decreases in other communicable disorders are likely to result in depressive disorders becoming the leading cause of disability and overall disease burden worldwide. Continuing debate and further scientific studies will be required to confirm and refine the findings of the GBD study. However, it is important to note several limitations of the study: The figures used to calculate the burden due to depressive disorders are very low compared with the recent findings from large-scale epidemiological studies, such as the (U.S.) National Comorbidity Survey [72] and the British national psychiatric morbidity survey.[73]

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World The GBD study considered unipolar depression to be an episodic illness, while current concepts of the disorder describe it as a chronic relapsing medical illness. Likewise, the study considered depression only as an adult disease, yet overwhelming evidence suggests that depression also occurs with considerable frequency in childhood and adolescence.[74] Only two disability weights were used to calculate the global burden of depressive disorders—one for treated cases, the other for untreated cases.[31] The impact of comorbidity of depression with other mental and substance abuse disorders was not addressed.[75] The burden on families, which is particularly significant for depression, was also not addressed. Given all of the above limitations, it is clear that the GBD estimates of the global burden of disability caused by depression are conservative at best, and more likely significantly underreport the worldwide burden exacted by depressive illness. Thus there is a pressing need for more precise information on the prevalence of and disability associated with these disorders in low-income countries. As noted above, the burden on family members of patients was not included in the GBD. However, the findings of several studies in both developed and developing countries reveal the significant toll exacted by depressive illness on family members and family stability.[ 76,77 and 78] Family members of depressed individuals may have increased rates of physical illness and frequent symptoms of fatigue.[79,80]. As described in Chapter 2, the stigma associated with mental illness is often great in both developed and developing countries. The burden of stigma is experienced not only by those who suffer from the illness, but also by their family members. This burden can lead to lost social and employment opportunities, social isolation, and unwillingness to assist the ill family member in seeking treatment.[81] A few studies in developed countries have begun to examine the cost to the workforce caused by depression. Findings indicate that depressive illness has resulted in more days of disability and lost work time than chronic physical conditions such as heart disease, hypertension, and lower back pain.[82,83] The governments and employers of developing countries would be likely to see similar results. Studies to determine this economic burden may reinforce the argument for robust, proactive efforts on the part of governments and communities to prevent and treat depression. Recommendation 9-1. Depressive disorders exhibit high incidence and prevalence in the developing world, lead to disability and mortality, and exact high social costs. Therefore, they should be given high national priority as a public health problem of relevance to all government ministries, and be accorded high local priority by district planning committees.

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World PREVALENCE AND INCIDENCE Over the last four decades, community surveys of mental disorders have provided diagnostic information, based on standardized methods of assessment, that permits comparison of research from different locations. Here we summarize selected epidemiological studies on depression conducted at the community level (Table 9-3) and on common mental disorders (which include depression) conducted at both the community (Table 9-4) and primary care (Table 9-5) levels. The accumulated evidence from these studies reveals the widespread prevalence of depression within both the developing and developed worlds, ranging from 8–43 percent. The variation in rates reported by these studies also appears to be due in part to cultural and environmental differences among the populations studied. Overall rates are higher in surveys of primary care attenders than in surveys of community populations. Precise case rates vary among locations and populations, and depend partly on the methodology used.[17,83] Differing rates of depression among population groups are discussed in greater detail in the subsequent discussion of risk factors. The most common psychiatric syndrome seen in community studies is a combination of depression and anxiety. For example, about one-half of those with a primary diagnosis of DSM-IV major depression also have an anxiety disorder.[84,85] This condition is sometimes referred to as comorbidity, but such a definition appears to be an artifact of classification systems designed primarily for hospital patients, rather than for the general population. When examined at the more universal level of primary care, anxiety and depression appear to coexist in the majority of depressed patients in both developing and developed countries.[86,87,88 and 89] Indeed, many mental health professionals now support the grouping of depression, anxiety, and other conditions often found to coexist in a single category—referred to as common mental disorders (CMD).[ 90,91,92 and 93] This chapter at times includes research that has examined CMD because it not only provides data that would eitherwise be absent, but also offers an accurate reflection of the high frequency with which these coexisting mental disorders occur. In addition to anxiety, several other conditions frequently coexist with depression; these include panic and dissociative disorders, neurasthenia, and sleep problems.[94] Recent studies rank CMD among the most important causes of morbidity in primary care settings.[95] For example, a review of the recent literature on CMD from South Asia [11] indicated that these disorders can be detected in more than a third of people who seek primary health care. A World Health Organization (WHO) collaborative study provided important information on the form, frequency, and outcome of psychological disorders seen in general health care settings. This study was carried out in 14 countries in different parts of the world: Brazil, Chile, the Federal Republic of Germany, France, Greece, India, Italy, Japan, the Netherlands, Nigeria, the People's Republic of China, Turkey, the United Kingdom, and the United States.[96] In the

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World study, 25,916 people aged 18 to 65 who consulted health care services were screened. Well-defined psychological problems were found in 24 percent of these subjects; most common were depressive disorders, anxiety disorders, alcohol use disorders, somatoform disorders, and neurasthenia. The results of the WHO study indicate a strong association between CMD and disability, defined as impairment of physical and social functioning. Disability levels were found to be greater on average among primary care patients with a psychological disorder than among those with common chronic diseases such as hypertension, diabetes, arthritis, and back pain. This finding of enhanced disability for psychological disorders was consistent across centers, across time, and across individual diagnoses.[33,34,97,98] The conditions categorized as CMD were also found frequently to be chronic. Approximately half of those with CMD when they first sought primary care continued to be afflicted a year later.[19] People with CMD frequently seek primary care for physical symptoms. The latter may either serve as a risk factor for mental illness or result from somatization of psychological symptoms. As a result, CMD contributes significantly to the workload in both primary health care clinics and specialty medical clinics (Table 9-5).[94,97,98]

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World TABLE 9-3 Selected Prevalence Studies of Depression Country Population Method Prevalence per 1,000 Population at Risk Lesotho [99] Rural village (n = 356); age 19–93 Sample survey Modules of DIS 88.5 South Africa [100] Rural village (n = 481); age > 18 Two-stage sample survey SRQ and PSE 180 Uganda [101] Two rural villages (n = 206); age > 18 Homestead survey PSE/SPI 143 males 226 females Taiwan [102] Rural   6 Taiwan [102] Urban, small town   11 Taiwan [102] Taipei (urban)   8 Taiwan [18] Urban and rural (n = 11,004); age 18–65 DIS 8 South Korea [18] National sample (n = 5,100); adults 18–65 DIS 23 India [103] Rural (n = 4,481) Interviews by trained field worker 430 India [104] Urban (n = 4,481) Interviews by field worker 10 China [105] (n = 388,136)   Neurotic depression, 0.37 affective psychosis, 13 neurasthenia Brazil [106] 3 urban localities Household survey 13–67 across different localities Dubai [107] Females (n = 300)   137 Australia [108] Canberra (n = 756) Household survey PSE 26 male 67 female 48 total United Kingdom [109] Camberwell (n = 800) Household survey PSE 48 male 90 female 70 total Holland [110] Nijmegen (n = 3,232) Household survey PSE 55 Finland [111] (n = 742) Household survey PSE 46 United Kingdom [112] Camberwell Cypriot community in inner London (n = 307) Household survey PSE 42 male 71 female 56 total Italy [113] Sardinia (n = 374) Household survey PSE 52 male 110 female 83 total United States of America [114] 48 contiguous states (n = 8098); age 15–54 Household survey 77 male 129 female annual prevalence United Kingdom [73] Sample of total population excluding Northern Ireland and the highlands and islands of Scotland (n = 10,1108); age 18–64 Household survey CIS-R and SCAN 18 male 27 female one week prevalence

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Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenge in the Developing World Summary of Findings: Stroke in Developing Countries Stroke ranked as the third leading cause of death in 1990 in developing countries and was responsible for about 2.4 percent of disability-adjusted life years (DALYs) worldwide. Projections for 2020 place stroke fifth among the causes of disease burden for developing countries. Prevalence and incidence rates for stroke vary dramatically among populations and may be influenced by economic, behavioral, and genetic factors, among others. Comparative epidemiological studies of stroke based on common definitions, methods, and modes of data presentation are needed to increase understanding of this disease. Because of the high risk for death, long-term disability, and recurrence after a first stroke, prevention is key to reducing the public health impacts of cerebrovascular disease. And prevention is feasible, given the remarkable reduction in stroke mortality achieved in several developed countries. Low-cost community health education programs that promote exercise, healthy diets, and smoking cessation may significantly reduce risk of stroke in developing countries. Several low-cost treatments for hypertension, diabetes, and other conditions are likely to reduce significantly the incidence and severity of stroke and stroke-related vascular disease in developing countries. Primary health care workers, nurses, and physicians play an important role in detecting, diagnosing, and treating hypertension and other conditions that increase stroke risk, and in ensuring compliance with treatment. Key resources such as stroke units in major hospitals, rehabilitation facilities, and post-stroke community support programs may serve a minority of patients, but promote the development and introduction of appropriate, cost-effective methods and technology for stroke prevention, treatment, and rehabilitation.