Mood Disorders
The cardinal features of mood disorders are pervasive abnormalities in the predominant emotional state of the person, such as depressed, elated, or irritable. In mood disorders, these core emotional symptoms are accompanied by abnormalities in physiology, such as changes in patterns of sleep, appetite, and energy, and by changes in cognition and behavior. In developing countries, concurrent somatic symptoms are also commonly reported and may be the chief complaint. A generally accepted subclassification of mood disorders distinguishes unipolar depressive disorders from bipolar disorder (defined by the occurrence of mania). This distinction is based on symptoms, course of illness, patterns of familial transmission, and treatment response.
Bipolar Disorder
Bipolar disorder is characterized by episodes of mania and depression, often followed by relative periods of healthy mood (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 cannot 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 symptomatically indistinguishable from those who have unipolar depressions alone. Unlike anxiety and unipolar mood disorders, 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 community 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 descriptions of bipolar disorder suggest recovery to baseline functioning between episodes, but many patients have residual symptoms 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 documented 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 epidemiological 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 superimposed 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 symptoms 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 prevalence 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 estimates 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 spectrum 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 associated with substantial impairments in both productive and social roles (Das Gupta and Guest 2002). Epidemiological evidence 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, recurrent 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 disorders 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 antipsychotic 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 duration of acute manic episodes. Maintenance treatment with two mood-stabilizing drugs—lithium and valproic acid (administered as sodium valproate)—has been shown to have 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 composite disability weight of 0.445 (Chisholm and others forthcoming). This estimate then was adjusted for expected nonadherence 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 valproic 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 studies 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 concentrating, 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 generally strongest with generalized anxiety disorder and panic disorder (Kessler and others 1996).
Epidemiology and Burden
Prevalence of nonbipolar depression has been estimated in a number of large-scale community epidemiological surveys. Lifetime prevalence estimates of having either major depressive disorder or dysthymia in these surveys 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 percent. 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 difficulties 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 (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 treatments for depression (Paykel and Priest 1992). The older tricyclic 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 psychosocial 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 developing 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 maintenance 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).
