Mental Disorders: Prevalence, Comorbidities, and Effective Treatments, Exams of Latin language

Download Mental Disorders: Prevalence, Comorbidities, and Effective Treatments and more Exams Latin language in PDF only on Docsity! 605 Mental disorders are diseases that affect cognition, emotion, and behavioral control and substantially interfere both with the ability of children to learn and with the ability of adults to function in their families, at work, and in the broader society. Mental disorders tend to begin early in life and often run a chronic recurrent course. They are common in all countries where their prevalence has been examined. Because of the combination of high prevalence, early onset, persistence, and impairment, mental disorders make a major contribution to total disease burden. Although most of the burden attributable to mental disorders is disability related, premature mortality, especially from suicide, is not insignificant. Table 31.1 summa- rizes discounted disability-adjusted life years (DALYs) for selected psychiatric conditions in 2001. Mental disorders have complex etiologies that involve inter- actions among multiple genetic and nongenetic risk factors. Gender is related to risk in many cases: males have higher rates of attention deficit hyperactivity disorder, autism, and sub- stance use disorders; females have higher rates of major depres- sive disorder, most anxiety disorders, and eating disorders. Biochemical and morphological abnormalities of the brain associated with schizophrenia, autism, mood, and anxiety dis- orders are being identified using approaches such as post- mortem analysis and noninvasive neuroimaging. Major world- wide efforts under way to identify risk-conferring genes for mental disorders are proving challenging, but initial results are promising. Identifying the gene or genes causing or creating vulnerability for a disorder should help us understand what goes wrong in the brain to produce mental illness and should have a clinical effect by contributing to improved diagnostics and therapeutics (Hyman 2000). Twin studies make it clear that environmental risk factors also play an important role in mental disorders; concordance for disease among identical twins, although substantially higher than among nonidentical twins, is still well below 100 percent (Kendler and others 2003). However, as is the case for genetic factors, investigation of environmental risk factors has proved difficult. For schizophrenia, where nongenetic components of risk may include obstetrical complications and season of birth (Mortensen and others 1999), perhaps as a proxy for infections early in life, research has been hampered by the modest proven effect of the nongenetic risk factors identified to date. For depression, anxiety, and substance use disorders, where envi- ronmental risk factors are more robust, adverse circumstances associated with risk, such as early childhood abuse, violence, poverty, and stress (Patel and Kleinman 2003) correlate with multiple disorders and could be affected by selection bias as well as by bias associated with self-reporting. Generalizable, prospec- tive cross-cultural studies are needed to delineate nongenetic risk factors more clearly. Posttraumatic stress disorder (PTSD) is the mental disorder for which clear environmental triggers are best documented. Even here, though, enormous interindividual variability occurs in the threshold of stress severity associated with PTSD as well as in the evidence from twin studies of genetic influences on stress reactivity in triggering PTSD. The last half of the 20th century saw enormous progress in the development of treatments for mental disorders. Beginning in the early 1950s, effective psychotropic drugs were discovered that treated the symptoms of schizophrenia, bipolar disorder, major depression, anxiety disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, and others. The safety and efficacy of antipsychotic, mood-stabilizing, Chapter 31 Mental Disorders Steven Hyman, Dan Chisholm, Ronald Kessler, Vikram Patel, and Harvey Whiteford antidepressant, anxiolytic, and stimulant drugs have been established through a large number of randomized clinical trials. Psychosocial treatments have been developed and tested using modern methodologies. Brief, symptom-focused psy- chotherapies such as cognitive-behavioral therapies have been shown to be efficacious for panic disorder, phobias, obsessive- compulsive disorder, and major depression. There is, however, an important caveat about the current knowledge base for treatment. As is the case for almost all of medicine, randomized clinical trials have been performed largely with highly selected populations in specialized research settings in industrial countries. A need exists to subject existing treatments to effectiveness trials in more representative popu- lations and diverse settings, especially in developing countries. That limitation notwithstanding, a substantial body of knowl- edge exists to guide treatment. It is particularly unfortunate, therefore, that timely diagnoses and the application of research-based treatments significantly lag behind the state of knowledge in industrial and developing countries alike. As a result, substantial opportunities exist to decrease the enormous burden attributable to mental disorders worldwide by closing the gap between what we know and what we do. Mental disorders are stigmatized in many countries and cultures (Weiss and others 2001). Stigma has been facilitated by the slow emergence of convincing scientific explanations for the etiologies of mental disorders and by the mistaken belief that symptoms are caused by a lack of will power or reflect some moral taint. Recent scientific findings combined with educa- tional efforts in some countries have begun to reduce the stigma (Rahman and others 1998), but shame and fear associated with 606 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others Table 31.1 Disease Burden of Selected Major Psychiatric Disorders, by World Bank Region World Bank region Sub-Saharan Latin America and Middle East and Europe and East Asia and High-income Africa the Caribbean North Africa Central Asia South Asia the Pacific countries World Total population (millions) 668 526 310 477 1,388 1,851 929 6,159 Total disease burden 344,754 104,287 65,570 116,502 408,655 346,941 149,161 1,535,870 (thousands of DALYs) Total neuropsychiatric 15,151 18,781 8,310 14,106 37,734 42,992 31,230 168,304 disease burden (thousands of DALYs) Total burden (thousands of discounted DALYs per year) Schizophrenia 1,146 1,078 696 778 2,896 3,934 1,115 11,643 Bipolar disorder 1,204 883 567 668 2,237 3,118 1,056 9,733 Depression 3,275 5,219 2,027 4,268 14,582 14,054 8,408 51,833 Panic disorder 519 409 264 340 1,081 1,401 536 4,550 Total burden (DALYs per year per 1 million population) Schizophrenia 1,716 2,049 2,247 1,630 2,087 2,126 1,201 1,894 Bipolar disorder 1,803 1,678 1,830 1,400 1,612 1,685 1,137 1,583 Depression 4,905 9,919 6,544 8,944 10,507 7,594 9,054 8,431 Panic disorder 777 777 852 713 779 757 577 740 Percentage of total disease burden Schizophrenia 0.33 1.03 1.06 0.67 0.71 1.13 0.75 0.76 Bipolar disorder 0.35 0.85 0.86 0.57 0.55 0.90 0.71 0.63 Depression 0.95 5.00 3.09 3.66 3.57 4.05 5.64 3.37 Panic disorder 0.15 0.39 0.40 0.29 0.26 0.40 0.36 0.30 Percentage of neuropsychiatric disease burden Schizophrenia 7.56 5.74 8.38 5.52 7.67 9.15 3.57 6.92 Bipolar disorder 7.95 4.70 6.82 4.74 5.93 7.25 3.38 5.78 Depression 21.62 27.79 24.39 30.26 38.64 32.69 26.92 30.80 Panic disorder 3.43 2.18 3.18 2.41 2.86 3.26 1.72 2.70 Source: WHO Global Burden of Disease 2001 estimates recalculated by World Bank region (http://www.fic.nih.gov/dcpp/gbd.html). (euthymia). Mixed states with symptoms of both mania and depression also occur. Mania is typically characterized by euphoria or irritability, a marked increase in energy, and a decreased need for sleep. Individuals with mania often exhibit intrusive, impulsive, and disinhibited behaviors. They may be excessively involved in goal-directed behaviors characterized by poor judgment; for example, a person might spend all funds to which he or she has access and more. Self-esteem is typically inflated, frequently reaching delusional proportions. Speech is often rapid and difficult to interrupt. Individuals with mania also may exhibit cognitive symptoms; patients can- not stick to a topic and may jump rapidly from idea to idea, making comprehension of their train of thought difficult. Psychotic symptoms are common during manic episodes. The depressive episodes of people with bipolar disorder are symp- tomatically indistinguishable from those who have unipolar depressions alone. Unlike anxiety and unipolar mood disor- ders, which are more common in women, bipolar disorder has an equal gender ratio of lifetime prevalence, although the ratio of depressive-to-manic episodes is higher among bipolar women than men. Natural History and Course. Retrospective reports from com- munity epidemiological surveys consistently show that bipolar disorder has an early age of onset (in the late teens through mid- 20s). Onset in childhood is increasingly recognized, although it remains controversial. Late onset is less common. The vast majority of patients with bipolar disorder have recurrent episodes of illness, both mania and depression. Classic descrip- tions of bipolar disorder suggest recovery to baseline function- ing between episodes, but many patients have residual symp- toms that may cause significant impairment (Angst and Sellaro 2000). These states of mania, depression, and lesser (or absent) symptoms are used in the intervention analysis below. The rate of cycling between mania and depression varies widely among individuals. One common pattern of illness is for episodes initially to be separated by a relatively long period, perhaps a year, and then to become more frequent with age. A minority of patients with four or more cycles per year, termed rapid cyclers, tend to be more disabled and less responsive to existing treatments. Once cycles are established, most acute episodes start without an identifiable precipitant; the best doc- umented exception is that manic episodes may be initiated by sleep deprivation, making a regular daily sleep schedule and avoidance of shift work important in management (Frank, Swartz, and Kupfer 2000). Bipolar disorder has consistently been found in epidemio- logical surveys to be highly comorbid with other psychiatric disorders, especially anxiety and substance use disorders (ten Have and others 2002). The extent of comorbidity is much greater than for unipolar depressive disorders or anxiety disorders. Some individuals with classic symptoms of bipolar disorder also exhibit chronic psychotic symptoms superim- posed on their mood syndrome. These individuals are said to have schizoaffective disorder. Their prognosis tends to be less favorable than for the usual bipolar patient, although somewhat better than for individuals with schizophrenia. Schizoaffective disorder may also be diagnosed when chronic psychotic symp- toms are superimposed on unipolar depression. Individuals with this combination of symptoms have outcomes similar to patients with schizophrenia (Tsuang and Coryell 1993). Epidemiology and Burden. Lifetime and 12-month preva- lence estimates of bipolar disorder have been reported from a number of community psychiatric epidemiological surveys. Lifetime prevalence estimates are in the range 0.1 to 2.0 percent (Vega and others 1998; Vicente and others 2002), with a weighted mean across surveys of 0.7 percent. Prevalence esti- mates for past-year episodes have a similarly wide range (0.1 to 1.3 percent) (Vega and others 1998) and a weighted mean of 0.5 percent. It is important to note that good evidence exists suggesting that bipolar disorder has a wide subthreshold spec- trum that includes people who are often seriously impaired even though they do not meet full DSM or ICD criteria for the disorder (Perugi and Akiskal 2002). This spectrum might include as much as 5 percent of the general population. The ratio of recent-to-lifetime prevalence of bipolar disorder in community surveys is quite high (0.71), indicating that bipolar disorder is persistent. Epidemiological data show that bipolar disorder is associ- ated with substantial impairments in both productive and social roles (Das Gupta and Guest 2002). Epidemiological evi- dence documents consistent delays in patients initially seeking professional treatment (Olfson and others 1998), especially among early-onset cases, as well as substantial undertreatment of current cases. Each of these characteristics—chronic, recur- rent course; significant impairments to functioning; modest treatment rates—contributes to estimates of aggregate disease burden that approach those for schizophrenia (1,200 to 1,800 DALYs lost per 1 million population, making up more than 5 percent of the burden attributable to neuropsychiatric disor- ders as a whole—see table 31.1). Interventions. Analyses of the primary treatment approaches for bipolar disorder are based on the three health states that characterize the disorder—mania, depression, and euthymia. Robust evidence from controlled trials shows that antipsychot- ic drugs and some benzodiazepines produce a relatively rapid reduction in symptoms of a manic phase. Mood-stabilizing drugs act more slowly, but they reduce the severity and dura- tion of acute manic episodes. Maintenance treatment with two mood-stabilizing drugs—lithium and valproic acid (adminis- tered as sodium valproate)—has been shown to have Mental Disorders | 609 significant, albeit partial, efficacy in reducing rates of both manic and depressive relapses. The drawback of lithium is that toxic levels are not much greater than therapeutic levels; thus, serum-level monitoring is required. For the cost-effectiveness analyses, lithium and valproic acid, which have empirical data supporting their efficacy in treating and preventing manic and depressive episodes, were considered. Because evidence suggests that psychosocial approaches enhance compliance with medication (Huxley, Parikh, and Baldessarini 2000), adjuvant strategies also were assessed. The primary treatment effect was a change in the population-level disability associated with bipolar disorder (a weighted average of time spent in a manic, depressed, or euthymic phase of illness). Both an acute treatment effect— calculated as the product of initial response and reduced episode duration—and a prophylactic treatment effect were ascribed to lithium and valproic acid, resulting in an estimated improvement of close to 50 percent over the untreated com- posite disability weight of 0.445 (Chisholm and others forth- coming). This estimate then was adjusted for expected nonad- herence to treatment in real-world clinical settings—slightly lower for lithium than for valproic acid (Bowden and others 2000). A secondary effect of treatment—reduction of the case fatality rate by two-thirds—was also ascribed to lithium, though, because of an absence of current evidence, not to val- proic acid (Goodwin and others 2003). This reduction was derived through a change in the standardized mortality ratio from 2.5 to 1.5, estimated on the basis of natural history stud- ies reported for the prelithium era (for example, Astrup, Fossum, and Holmboe 1959; Helgason 1964) to the postlithium era (for example, Goodwin and others 2003). Major Depressive Disorder The core symptom of major depression is a disturbance of mood; sadness is most typical, but anger, irritability, and loss of interest in usual pursuits may predominate. Often the affected person is unable to experience pleasure (anhedonia) and may feel hopeless. In many countries of the developing world, patients will not complain of such emotional symptoms, but rather of physical symptoms, such as fatigue or multiple aches and pains. Typical physiological symptoms that occur across cultures include sleep disturbance (most often insomnia with early morning awakening, but occasionally excessive sleeping); appetite disturbance (usually loss of appetite and weight loss, but occasionally excessive eating); and decreased energy. Behaviorally, some individuals with depression exhibit slowed motor movements (psychomotor retardation), whereas others may be agitated. Cognitive symptoms may include thoughts of worthlessness and guilt, suicidal thoughts, difficulty concen- trating, slow thinking, and poor memory. Psychotic symptoms occur in a minority of cases. Natural History and Course. Major depression is an episodic disorder that generally begins early in life (median age of onset in the mid to late 20s in community epidemiological surveys), although new onsets can be observed across the lifespan. Childhood onset is being increasingly recognized, although not all childhood precursors of adult depression take the form of a clear depressive disorder. Most individuals suffering from a depressive episode will have a recurrence (Mueller and others 1999), with recurrence risk greater among those with early- onset disease. Many individuals do not recover completely from their acute episodes and have chronic milder depression punctuated by acute exacerbations (Judd and others 1998). The current term for chronic, milder depression lasting more than two years is dysthymia. Although the symptoms of minor depression are, by definition, less severe than those of a major depressive episode, chronicity ultimately makes even this lesser form of the illness very disabling in many cases (Judd, Schettler, and Akiskal 2002). Depression has consistently been found in epidemiological surveys to be highly comorbid with other mental disorders, with roughly half the people who have a history of depression also having a lifetime anxiety disorder. Comorbidities of depression and anxiety disorders are genera- lly strongest with generalized anxiety disorder and panic disorder (Kessler and others 1996). Epidemiology and Burden. Prevalence of nonbipolar depres- sion has been estimated in a number of large-scale community epidemiological surveys. Lifetime prevalence estimates of hav- ing either major depressive disorder or dysthymia in these sur- veys are in the range 4.2 to 17.0 percent (Andrade and others 2003; Bijl and others 1998), with a weighted mean of 12.1 per- cent. Six- to 12-month prevalence estimates have a similarly wide range (1.9 to 10.9 percent) (Andrade and others 2003; Robins and Regier 1991), with a weighted mean of 5.8 percent. These wide differences in prevalence likely represent the difficul- ties inherent in self-reporting of conditions that are invariably stigmatized across cultures.Prevalence estimates are consistently highest in North America and lowest in Asia (with prevalence estimates of major depressive disorders generally a good deal higher than those of dysthymia). Epidemiological data document consistent delays in patients initially seeking professional treatment for depression, especially among early-onset cases (Olfson and others 1998), as well as substantial undertreatment. For example, World Mental Health surveys in six Western European countries found that only 36.6 percent of people with active nonbipolar depression in the 12 months before the survey received any professional treatment for this disorder during the subsequent year 610 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others Mental Disorders | 611 (ESEMeD/MHEDEA 2000 Investigators 2004). The situation is even worse in developing countries, where the vast majority of people with depression who seek help do so in general health care settings and complain of nonspecific physical symptoms. Such individuals receive a correct diagnosis in less than one-quarter of cases and typically are treated with medicines of doubtful efficacy (Linden and others 1999). Depression is consistently found in community surveys to be associated with substantial impairments in both productive and social roles (Wang, Simon, and Kessler 2003). As with bipolar depression, but exacerbated by its high incidence, the recurrent nature and disabling consequences of (unipolar) depression mean that overall disease burden estimates are high in all regions of the world (5,000 to 10,000 DALYs per 1 million population, as much as 5 percent of the total burden of disease from all causes; table 31.1). Depression is, in fact, ranked as the fourth leading cause of disease burden globally and represents the single largest contributor to nonfatal burden (Ustun and others 2004). Interventions. Efficacy has been demonstrated for several classes of antidepressant drugs and for two psychosocial treat- ments for depression (Paykel and Priest 1992). The older tri- cyclic antidepressants (TCAs) and newer drugs, including the selective serotonin reuptake inhibitors (SSRIs), have similar efficacy. The newer drugs have milder side-effect profiles and are consequently more likely to be tolerated at therapeutic doses (Pereira and Patel 1999). SSRIs have not been widely used in developing countries because of their higher cost, although as the patent protection expires, this situation is likely to change (Patel 1996). Of the psychosocial treatments with demonstrated efficacy, the most widely accepted are cognitive- behavioral approaches. Alone or in combination, drug and psy- chosocial treatments speed recovery from acute episodes. Maintenance treatment with drugs decreases relapse risk (Geddes and others 2003). Some evidence suggests that a course of psychotherapy may also delay relapses. Although most of the clinical trials have been carried out in industrial countries, at least three high-quality trials have demonstrated the efficacy of antidepressants, group therapy, or both in devel- oping countries (Araya and others 2003; Bolton and others 2003; Patel and others 2003). For the cost-effectiveness analyses, depression was modeled as an episodic disorder with a high rate of remission and subsequent recurrence, and with excess mortality from suicide (Chisholm and others 2004). None of the selected depression interventions was accorded a reduction in case fatality, however, owing to the lack of robust clinical evidence that antidepressants or psychotherapy in themselves alter the relative risk of death by suicide (Storosum and others 2001). The main modeled impact of intervention targeted toward episodic treatment of a new depressive episode was a reduction in the duration of time depressed, equivalent to an increase in the remission rate (25 to 40 percent improvement over no treatment; Malt and others 1999; Solomon and others 1997). In addition, all interventions were attributed a modest improvement in the level of disability for an unremitted depressive episode (10 to 15 percent), resulting from increased proportions of cases moving from more to less severe health states. For the estimated 56 percent of prevalent cases eligible for maintenance treatment (at least two lifetime episodes), an additional effect of efficacious mainte- nance treatment was incorporated into the analysis by reducing the incidence of recurrent episodes by 50 percent (Geddes and others 2003). Estimates of intervention effectiveness include the positive change that would occur naturally and also incorporate any placebo effect, which, in the treatment of depression, is not inconsiderable (Andrews 2001). ANXIETY DISORDERS Anxiety disorders are a group of disorders that have as their central feature the inability to regulate fear or worry. Although anxiety in itself is likely to feature in the clinical presentation of most patients, somatic complaints such as chest pain, palpita- tions, respiratory difficulty, headaches, and the like are also common, and these symptoms may be more common in developing countries. A number of different types of anxiety disorder exist, some of which are now briefly described. The central feature of panic disorder is an unexpected panic attack, which is a discrete period of intense fear accompanied by physiologic symptoms such as a racing heart, shortness of breath, sweating, or dizziness. The person may have an intense fear of losing control or of dying. Panic disorder is diagnosed when panic attacks are recurrent and give rise to anticipatory anxiety about additional attacks. People with panic disorder may progressively restrict their lives to avoid situations in which panic attacks occur or situations from which it might be difficult to escape should a panic attack occur. They common- ly avoid crowds, traveling, bridges, and elevators, and ultimate- ly some individuals may stop leaving home altogether. Pervasive phobic avoidance is described as agoraphobia. Generalized anxiety disorder is characterized by chronic unrealistic and excessive worry. These symptoms are accompa- nied by specific anxiety-related symptoms such as sympathetic nervous system arousal, excessive vigilance, and motor tension. Posttraumatic stress disorder follows serious trauma. It is characterized by emotional numbness, punctuated by intrusive reliving of the traumatic episode, generally initiated by envi- ronmental cues that act as reminders of the trauma; by dis- turbed sleep; and by hyperarousal, such as exaggerated startle responses. coverage. Costs incurred over the 10-year implementation peri- od were discounted at 3 percent and expressed in U.S. dollars (rather than international dollars, which attempt to adjust for differences in purchasing power between countries). Coverage In each World Bank region, treatment costs and effects were ascribed to the population in need, both at current levels of intervention coverage and at a scaled-up, target level of coverage (80 percent for schizophrenia, 50 percent for the other conditions). Target coverage levels were predicated on the basis of what could feasibly be achieved given existing rates of treat- ment (Ferri and others 2004; Kohn and others 2004), as well as on prerequisites for increased coverage, such as recognition of common mental disorders in primary care. Estimation of cur- rent regional levels of effective coverage is hampered by lack of data; nevertheless, an attempt was made to approximate the expected proportion of the diseased population receiving evidence-based pharmacological and psychosocial treatments (Ferri and others 2004; Kohn and others 2004), plus those in contact with traditional healers (the effectiveness of which was conservatively approximated by ascribing a placebo effect size for each disorder). Results Tables 31.3 through 31.6 provide estimates of the population- level effects (measured in DALYs averted), costs, and cost- effectiveness of each intervention by world region for the four types of psychiatric disorder considered in this chapter. A num- ber of key findings emerge from this analysis. Treatment Effectiveness. Results for schizophrenia and bipo- lar disorder are similar (albeit at differing coverage levels), rang- ing from less than 100 DALYs averted per 1 million population under the current situation in Sub-Saharan Africa and South Asia to 350 to 400 DALYs averted per 1 million population for 614 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others Table 31.2 Interventions for Reducing the Burden of Major Psychiatric Disorders in Developing Countries Disorder Intervention Example Schizophrenia Treatment setting: hospital outpatient Treatment coverage (target): 80 percent Bipolar affective disorder Treatment setting: hospital outpatient Treatment coverage (target): 50 percent Depression Treatment setting: primary health care Treatment coverage (target): 50 percent Panic disorder Treatment setting: primary health care Treatment coverage (target): 50 percent Older (neuroleptic) antipsychotic drug Newer (atypical) antipsychotic drug Older antipsychotic drug and psychosocial treatment Newer antipsychotic drug and psychosocial treatment Older mood-stabilizing drug Newer mood-stabilizing drug Older mood-stabilizing drug and psychosocial treatment Newer mood-stabilizing drug and psychosocial treatment Episodic treatment Older TCA Newer antidepressant drug (SSRI; generic) Psychosocial treatment Older antidepressant drug and psychosocial treatment Newer antidepressant drug and psychosocial treatment Maintenance treatment Older antidepressant drug and psychosocial treatment Newer antidepressant drug and psychosocial treatment Benzodiazepines Older TCA Newer antidepressant drug (SSRI; generic) Psychosocial treatment Older antidepressant drug and psychosocial treatment Newer antidepressant drug and psychosocial treatment Haloperidol Risperidone Haloperidol plus family psychoeducation Risperidone plus family psychoeducation Lithium carbonate Sodium valproate Lithium plus family psychoeducation Valproate plus family psychoeducation Imipramine or amitriptyline Fluoxetine Group psychotherapy Amitriptyline plus group psychotherapy Fluoxetine plus group psychotherapy Imipramine plus group psychotherapy Fluoxetine plus group psychotherapy Alprazolam Amitriptyline Fluoxetine Cognitive therapy Amitriptyline plus cognitive therapy Fluoxetine plus cognitive therapy Source: Authors’ own estimates and recommendations. Note: Interventions in bold are the most cost-effective treatments of choice. Mental Disorders | 615 Table 31.3 Cost-Effectiveness Results: Schizophrenia Model definition: World Bank region Treatment setting: (a) hospital- based; (b) community-based Sub-Saharan Latin America Middle East and Europe and East Asia and Treatment coverage: 80 percent Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Current situation 74 136 115 258 87 148 Older (neuroleptic) antipsychotic drug 149 219 214 254 177 231 Newer (atypical) antipsychotic drug 160 235 230 273 190 248 Older antipsychotic drug plus 254 373 364 353 300 392 psychosocial treatment Newer antipsychotic drug plus 261 383 373 364 308 403 psychosocial treatment Total cost (US$ million per year per 1 million population) Current situation 0.42 2.07 1.31 3.13 0.51 1.11 Hospital-based service model Older (neuroleptic) antipsychotic drug 0.60 3.09 2.40 2.24 0.74 1.18 Newer (atypical) antipsychotic drug 2.80 6.33 5.41 6.16 3.36 4.63 Older antipsychotic drug plus 0.67 3.27 2.56 2.36 0.81 1.26 psychosocial treatment Newer antipsychotic drug plus 2.87 6.56 5.61 6.31 3.44 4.73 psychosocial treatment Community-based service model Older (neuroleptic) antipsychotic drug 0.40 1.58 1.42 1.17 0.44 0.66 Newer (atypical) antipsychotic drug 2.59 4.85 4.45 5.11 3.07 4.12 Older antipsychotic drug plus 0.47 1.81 1.61 1.32 0.52 0.75 psychosocial treatment Newer antipsychotic drug plus 2.67 5.09 4.66 5.28 3.16 4.22 psychosocial treatment Cost-effectiveness (US$ per DALY averted) Current situation 5,695 15,192 11,400 12,134 5,900 7,533 Hospital-based service model Older (neuroleptic) antipsychotic drug 4,047 14,123 11,205 8,793 4,164 5,120 Newer (atypical) antipsychotic drug 17,433 26,893 23,543 22,530 17,702 18,700 Older antipsychotic drug plus 2,623 8,781 7,040 6,685 2,693 3,212 psychosocial treatment Newer antipsychotic drug plus 10,996 17,146 15,027 17,329 11,164 11,746 psychosocial treatment Community-based service model Older (neuroleptic) antipsychotic drug 2,668 7,230 6,618 4,595 2,499 2,855 Newer (atypical) antipsychotic drug 16,174 20,583 19,352 18,685 16,178 16,622 Older antipsychotic drug plus 1,839 4,847 4,431 3,745 1,743 1,917 psychosocial treatment Newer antipsychotic drug plus 10,232 13,313 12,485 14,481 10,239 10,484 psychosocial treatment Source: Authors’ own estimates. Note: Intervention data in bold are the most cost-effective treatments of choice. 616 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others Table 31.4 Cost-Effectiveness Results: Bipolar Disorder Model definition: World Bank region Treatment setting: (a) hospital- based; (b) community-based Sub-Saharan Latin America Middle East and Europe and East Asia and Treatment coverage: 50 percent Africa and the Caribbean North Africa Central Asia South Asia the Pacific Total effect (DALYs averted per year per 1 million population) Current situation 79 128 97 199 93 153 Older mood-stabilizing drug (lithium) 292 336 296 381 319 389 Newer mood-stabilizing drug 211 300 273 331 278 351 (valproate) Older mood-stabilizing drug plus 312 365 322 413 346 422 psychosocial treatment Newer mood-stabilizing drug plus 232 330 300 365 306 386 psychosocial treatment Total cost (US$ million per year per 1 million population) Current situation 0.31 1.22 0.74 1.27 0.42 0.67 Hospital-based service model Older mood-stabilizing drug (lithium) 0.61 2.77 1.92 2.03 0.82 1.30 Newer mood-stabilizing drug 0.79 2.87 2.04 2.20 1.03 1.53 (valproate) Older mood-stabilizing drug plus 0.63 2.79 1.95 2.05 0.84 1.32 psychosocial treatment Newer mood-stabilizing drug plus 0.81 2.90 2.08 2.22 1.06 1.55 psychosocial treatment Community-based service model Older mood-stabilizing drug (lithium) 0.46 1.78 1.20 1.37 0.59 0.93 Newer mood-stabilizing drug 0.64 1.91 1.36 1.57 0.82 1.17 (valproate) Older mood-stabilizing drug plus 0.48 1.80 1.23 1.39 0.62 0.95 psychosocial treatment Newer mood-stabilizing drug plus 0.67 1.95 1.39 1.59 0.85 1.19 psychosocial treatment Cost-effectiveness (US$ per DALY averted) Current situation 3,967 9,518 7,668 6,398 4,463 4,373 Hospital-based service model Older mood-stabilizing drug (lithium) 2,091 8,246 6,478 5,341 2,553 3,348 Newer mood-stabilizing drug 3,727 9,579 7,501 6,648 3,709 4,358 (valproate) Older mood-stabilizing drug plus 2,016 7,644 6,036 4,957 2,424 3,119 psychosocial treatment Newer mood-stabilizing drug plus 3,480 8,800 6,937 6,100 3,459 4,016 psychosocial treatment Community-based service model Older mood-stabilizing drug (lithium) 1,587 5,295 4,068 3,608 1,862 2,394 Newer mood-stabilizing drug 3,057 6,386 4,971 4,727 2,943 3,338 (valproate) Older mood-stabilizing drug plus 1,545 4,928 3,823 3,359 1,787 2,241 psychosocial treatment Newer mood-stabilizing drug plus 2,874 5,908 4,645 4,359 2,765 3,092 psychosocial treatment Source: Authors’ own estimates. Note: Intervention data in bold are the most cost-effective treatments of choice. With the exception of Europe and Central Asia, less than 10 per- cent of the disease burden currently is being averted, whereas the implementation of combined interventions at a scaled-up level of coverage is expected to avert 14 to 22 percent of the burden of schizophrenia (coverage level, 80 percent) and 17 to 29 percent of the burden of bipolar disorder (coverage level, 50 percent). For primary care treatment of common mental disorders, including depression and panic disorder, current levels of effec- tive coverage avert only 3 to 8 percent of the existing disease burden, whereas scaling up of the most effective interventions to a coverage level of 50 percent could be expected to avert more than 20 percent of the burden of depression and up to one-third of the burden of panic disorder. Considered at a pop- ulation level, episodic treatments for depressive episodes did not differ substantially within regions (averting 10 to15 percent of current burden); more substantial health gain is expected by providing maintenance treatment to individuals with recur- rent depression (approximately 1,200 to 1,900 DALYs averted per 1 million population; 18 to 23 percent of burden). Such an approach has been found to reduce the risk of relapse by half. Although the evidence to date from developing regions is mea- ger, our results suggest that SSRIs such as fluoxetine, alone or in combination with psychosocial treatment, are the most effec- tive treatments for panic disorder, with health gains consider- ably better than those estimated for benzodiazepine anxiolytic drugs such as alprazolam. Treatment Costs. Community-based service models for schizophrenia and bipolar disorder were found to be apprecia- bly less costly than hospital-based service models (for example, interventions for bipolar disorder were 25 to 40 percent less costly). The total cost per capita of community-based outpa- tient treatment with first-generation antipsychotic or mood- stabilizing drugs, including all patient-level resource needs as well as infrastructural support, ranged from US$0.40 to US$0.50 in Sub-Saharan Africa and South Asia to US$1.20 to US$1.90 in Latin America and the Caribbean and in Europe and Central Asia (equivalent patient costs per year, US$170 to US$300 and US$300 to US$800, respectively). The cost per capita for interventions using second-generation (atypical) antipsychotic drugs still under patent is much higher (US$2.50 to US$5.00). By contrast, some of the newer antidepressant drugs (SSRIs) are now off patent, and their use in treating depression and panic disorder was accordingly costed at their generic, nonbranded price. The patient-level cost of treating a 6-month episode of depression ranged from as little as US$30 (older antidepressants in Sub-Saharan Africa or South Asia) to US$150 (newer antidepressants in combination with brief psy- chotherapy in Latin America and the Caribbean). Total annual costs for all incidents of depressive episodes receiving treat- ment, including training and other program-level costs, were as much as US$2 to US$5 per capita for a maintenance treatment program using newer antidepressants, three times more costly than episodic treatment with newer antidepressant drugs only. Patient-level resource inputs for panic disorder interventions cost US$50 to US$200 per case per year, and overall costs including program costs of training and administration amounted to US$0.10 to US$0.30 per capita. Cost-Effectiveness. Compared with both the current situation and the epidemiological situation of no treatment (natural his- tory), the most cost-effective strategy for averting the burden of psychosis and severe affective disorders in developing countries is expected to be a combined intervention of first-generation antipsychotic or mood-stabilizing drugs with adjuvant psy- chosocial treatment delivered through a community-based outpatient service model, with a cost-effectiveness ratio of below US$2,000 in Sub-Saharan Africa and South Asia, rising to US$5,000 in Latin America and the Caribbean (equivalent to more than 500 DALYs averted per US$1 million expenditure in Sub-Saharan Africa and South Asia and 200 DALYs averted in Latin America and the Caribbean). Currently, the high acquisi- tion price of second-generation antipsychotic drugs makes their use in developing regions questionable on efficiency grounds, although this situation can be expected to change as these drugs come off patent. By contrast, evidence indicates that the relatively modest additional cost of adjuvant psy- chosocial treatment reaps significant health gains, thereby making such a combined strategy for schizophrenia and bipolar disorder treatment more cost-effective than pharma- cotherapy alone. For more common mental disorders treated in primary care settings (depressive and anxiety disorders), the single most cost-effective strategy is the scaled-up use of older antidepres- sants (because of their lower cost but similar efficacy compared with newer antidepressants). However, as the price margin between older and generic newer antidepressants continues to diminish, generic SSRIs—which have milder side effects and are more likely to be taken at a therapeutic dose (Pereira and Patel 1999)—can be expected to be at least as cost-effective and, therefore, the pharmacological treatment of choice in the future. Because depression is often a recurring condition, proactive care management, including long-term maintenance treatment with antidepressant drugs, represents a cost-effective way of significantly reducing the enormous burden of depres- sion that exists in developing regions now (400 to 1,300 DALYs averted per US$1 million expenditure). POLICY AND SERVICE IMPLICATIONS Many attempts have been made during the past 50 years to have mental health care placed higher on national and interna- tional agendas. In 1974, a WHO Expert Committee on the Mental Disorders | 619 Organization of Mental Health Services in Developing Countries (WHO 1975) made the following recommendations: • Develop a national mental health policy and create a unit within the Health Ministry to implement it. • Budget for workforce development, essential drug procure- ment, infrastructure development, data collection, and research. • Decentralize service provision and integrate mental health into primary health care. • Train and supervise primary health care providers in mental health using specialist mental health staff. Thirty years later, international agencies, nongovernmental organizations, and professional bodies continue to make those exact recommendations. One reason for the lack of action in mental health has been the paucity of information on the cost- effectiveness of mental health interventions. Advocacy without the necessary science can readily be ignored in countries with massive health problems and meager resources. This chapter aims to address this deficiency. Symptoms of mental disorders are often attributed to other illnesses, and mental disorders are often not considered health problems (Jacob 2001). Many nonscientific explanations for mental illness exist, and stigma exists to varying degrees every- where (Weiss and others 2001) with widespread delays or fail- ure to seek appropriate care (James and others 2002). When care is sought, a hierarchy of interventions comes into play, ranging from self-help, informal community support, tra- ditional healers, primary health care, specialist community mental health care, and psychiatric units in general hospitals to specialist long-stay mental hospitals. The mix of interventions depends on the availability of resources within a country or region (Saxena and Maulik 2003). The more resource- constrained the country or region is, the greater is the reliance on self-help, informal community support (especially family- based), and primary health care. Traditional healers are often the first source individuals with mental illness and their families turn to for professional assis- tance (see, for example, Abiodun 1995). A recent review of com- mon mental disorders among primary health clinics and tradi- tional healers in urban Tanzania showed that the prevalence of common mental disorders among those attending traditional healers was double that of patients at primary health care centers (Ngoma, Prince, and Mann 2003). Traditional healers are a het- erogeneous group and include faith healers, spiritual healers, religious healers, and practitioners of indigenous or alternative systems of medicine. In some countries, they are part of the informal health sector, but in other countries, traditional healers charge for their services and should be considered part of the private health care sector. Often, traditional healers have high acceptability and are accessible; at times, traditional healers work closely (and apparently effectively) with conventional mental health services (Thara, Padmavati, and Srinivasan 2004). Alternatively, animosity and competition can exist, and recent examples of human rights violations by traditional healers demonstrate the heterogeneity of this group of providers. The formal diagnosis and treatment of mental disorders occur in both primary and specialist health services. Examples in nearly a dozen countries now show it is feasible and practi- cable to treat common mental disorders in primary health care settings (for example, Chisholm and others 2000; De Jong 1996; Mohit and others 1999). The challenge is to enhance sys- tems of care by taking effective local models and disseminating them throughout a country. Concern has been expressed that the more sophisticated psychotherapies used in mental health care are beyond the human resources of developing countries. However, basic psy- chological therapies can be effective, though there is some evi- dence, at least for depression, that the newer drug therapies are more cost-effective than psychological therapies (Patel and others 2003). Psychoeducational family intervention has been shown to be suitable for rehabilitation in schizophrenia in rural China (Ran and others 2003) and to be cost-effective compared with other standard treatment (Xiong and others 1994). Evidence also shows that nurses can replace physicians as pri- mary health care providers in certain circumstances without loss of effectiveness (Climent and others 1978). Primary care practitioners need support to develop skills and experience in diagnosing and treating mental disorders: they need a sustain- able supply of medicines, access to supervision, and incentives to see patients with mental illness (Abas and others 2003). Community approaches using low-cost, locally available resources may improve treatment adherence and clinical out- comes even in rural and underresourced settings (Chatterjee and others 2003; Srinivasa Murthy and others 2005). In most countries, acute inpatient beds are being moved from mental hospitals into general or district hospitals. Although this policy potentially improves accessibility and increases the links with, and support provided to, primary mental health care, concerns can be raised as to whether gen- eral hospitals can adapt to provide adequate services to people with severe mental disorders. However, such services have been effectively established in a number of countries (see, for example, Alem and others 1999; Kilonzo and Simmons 1998), showing this form of service delivery to be feasible when it is clinically indicated. Nongovernmental organizations are important providers of mental health care. An estimated 93 percent of African and 80 percent of Southeast Asian countries have nongovernmental organizations in the mental health sector. They provide diverse services—including advocacy, informal support, housing, suicide prevention, substance misuse counseling, dementia support, rehabilitation, research, and other programs—that 620 | Disease Control Priorities in Developing Countries | Steven Hyman, Dan Chisholm, Ronald Kessler, and others complement, or in some cases substitute for, public and private clinical services (Levkoff, Macarthur, and Bucknall 1995; Patel and Thara 2003). Services for children and adolescents, the majority of the population in many developing countries, are even more defi- cient than those for adults. Priority needs to be given to these services (Rahman and others 2000). At the other end of the life spectrum, many developing countries are facing aging popula- tions with grossly underdeveloped aged care services (Levkoff, Macarthur, and Bucknall 1995). The high level of civil conflict and natural disasters requires attention to postconflict and posttrauma mental health conditions. The prevalence of these disorders is demonstrated by a recent study (Livanou, Basoglu, and Kalendar 2002) showing that, of 1,000 survivors of the August 1999 earthquake in Turkey, the incidence of PTSD was 63 percent and of depression was 42 percent. Specialist mental health providers, especially mental hospi- tals, tend to focus the services they provide on the lower- prevalence, higher-disability disorders, such as schizophrenia and bipolar disorder. Modern treatments, if available and used, allow most patients to be treated effectively out of hospital. Specifically, the use of antipsychotic and mood-stabilizing drugs and the development of strategies for community-based treatment have led to the closing of large numbers of psychi- atric inpatient beds in many countries and their replacement with community services and general hospital psychiatric units (for example, Larrobla and Botega 2001). However, in some countries, the majority of psychotic patients remain in long-term inpatient facilities that engage in custodial care, which is often of poor quality; moreover, basic rights are often violated at such facilities (van Voren and Whiteford 2000). Even if the quality of care is reasonable, acces- sibility is a problem: these hospitals are often situated in urban areas, but populations are largely rural and have limited trans- portation (Saraceno and others 1995). Furthermore, the con- centration of resources in these facilities can leave little for other service components (Gallegos and Montero 1999). For example, in Indonesia, 97 percent of the mental health budget is spent on public mental hospitals (Trisnantoro 2002). For many developing countries, the debate about the role of, or problems with, mental hospitals is subsumed within a gross deficiency of psychiatric beds of any kind. The priority for virtually all countries is generating suffi- cient resources for primary mental health care and deciding how to expand and best use scarce specialist resources. The quality of care is often very poor, and huge variations exist in resource availability between countries (Saxena and Maulik 2003; WHO 2001). Very few countries have what could be con- sidered an optimal mix of these services, and there are no uni- versally accepted planning parameters. However, conceptual models for developing national mental health policy and guidelines for service planning exist that can be useful in developing countries (Tansella and Thornicroft 1998; Townsend and others 2004; WHO 2003). CONCLUSION: PUBLIC SUPPORT FOR A COST-EFFECTIVE INTERVENTION PACKAGE In developing countries, much of the mental health care spend- ing is reported to be out of pocket. Individuals purchase mod- ern and traditional treatments if they can afford to do so. Although a large private health sector exists in low-income countries (Mills and others 2002), the quality and cost vary. Although unregulated markets fail in health, they fail even more in mental health. It is unlikely that a country will be able to rely on an unregulated private sector to deliver services that will reduce the burden of mental disorders. In addition to being a large and growing component of dis- ease burden, mental disorders meet virtually all the criteria by which we determine the need for government involvement in health care (Beeharry and others 2002). They affect the poor, cause externalities, and inflict catastrophic costs; moreover, pri- vate demand is inadequate. Indeed, the authors recognize that the main measure of outcome used in this and other chapters— the disability-adjusted life year—is limited to capturing change in service user–level symptoms, disability, recovery, and case- fatality. The DALY does not capture the positive change that treatment may have on a number of other significant conse- quences of mental disorders, including family burden (in par- ticular, productive time and household resources given up in the care of the sick family member) and lost productivity, at the level of both the individual and the household (treatment accel- erates return to paid work or usual household activities) and, by implication, at the level of society in general. The evidence base for these productivity increases, although modest in volume, constitutes an important additional argument alongside “cost per DALY” considerations for investing in mental health. The total budgetary requirements and health consequences of a cost-effective package of mental health care can begin to be mapped out by selecting one intervention for each of the four disorders considered in this chapter. 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