Depressive Disorders
The Merck Manuals, Online Medical Library
Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and sometimes by decreased interest or pleasure in activities. Exact cause is unknown but probably involves heredity, changes in neurotransmitter levels, altered neuroendocrine function, and psychosocial factors. Diagnosis is based on history. Treatment usually consists of drugs, psychotherapy, or both, and sometimes electroconvulsive therapy.
The term depression is often used to refer to any of several depressive disorders. Three are classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) by specific symptoms: major depressive disorder (often called major depression), dysthymia, and depressive disorder not otherwise specified. Two others are classified by etiology: depressive disorder due to a general physical condition and substance-induced depressive disorder.
Depressive disorders occur at any age but typically develop during the mid teens, 20s, or 30s. In primary care settings, as many as 30% of patients report depressive symptoms, but < 10% have major depression.
The term depression is often used to describe the low or discouraged mood that results from disappointments or losses. However, a better term for such a mood is demoralization. The negative feelings of demoralization, unlike those of depression, resolve when circumstances or events improve; the low mood usually lasts days rather than weeks or months, and suicidal thoughts and prolonged loss of function are much less likely.
Etiology
Exact cause is unknown. Heredity has an uncertain role; depression is more common among 1st-degree relatives of depressed patients, and concordance between identical twins is high. Hereditary genetic polymorphisms for the serotonin transporter active in the brain may be triggered by stress. People who have a history of child abuse or other major life stresses and have the short allele for this transporter are about twice as likely to develop depression as those who have the long allele.
Other theories focus on changes in neurotransmitter levels, including abnormal regulation of cholinergic, catecholaminergic (noradrenergic or dopaminergic), and serotonergic (5-hydroxytryptamine) neurotransmission. Neuroendocrine deregulation may be a factor, with particular emphasis on 3 axes: hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, and growth hormone.
Psychosocial factors also seem involved. Major life stresses, especially separations and losses, commonly precede episodes of major depression; however, such events do not usually cause lasting, severe depression except in people predisposed to a mood disorder.
People who have had an episode of major depression are at higher risk of subsequent episodes. People who are introverted and who have anxious tendencies may be more likely to develop a depressive disorder. Such people often lack the social skills to adjust to life pressures. Depression may also develop in people with other mental disorders.
Women are at higher risk, but no theory explains why. Possible factors include greater exposure to or heightened response to daily stresses, higher levels of monoamine oxidase (the enzyme that degrades neurotransmitters considered important for mood), and endocrine changes that occur with menstruation and at menopause. In postpartum depression (see Postpartum Care: Mental Disorders.), symptoms develop within 4 wk after delivery; endocrine changes have been implicated, but the specific cause is unknown. Also, thyroid function is more commonly dysregulated in women.
In seasonal affective disorder, symptoms develop in a seasonal pattern, typically during autumn or winter; the disorder tends to occur in climates with long or severe winters. Depressive symptoms or disorders may occur with various physical disorders, including thyroid and adrenal gland disorders, benign and malignant brain tumors, stroke, AIDS, Parkinson's disease, and multiple sclerosis (see Table 1: Mood Disorders: Some Causes of Symptoms of Depression and Mania) Certain drugs, such as corticosteroids, some β-blockers, antipsychotics (especially in the elderly), and reserpine, can also result in depressive disorders. Abuse of some recreational drugs (eg, alcohol, amphetamines) can lead to or accompany depression. Toxic effects or withdrawal of drugs may cause transient depressive symptoms.
Symptoms and Signs
Depression causes cognitive, psychomotor, and other types of dysfunction (eg, poor concentration, fatigue, loss of sexual desire, menstrual abnormalities) as well as a depressed mood. Other mental symptoms or disorders (eg, anxiety and panic attacks) commonly coexist, sometimes complicating diagnosis and treatment. Patients with all forms of depression are more likely to abuse alcohol or other recreational drugs in an attempt to self-treat sleep disturbances or anxiety symptoms; however, depression is a less common cause of alcoholism and drug abuse than was once thought. Patients are also more likely to become heavy smokers and to neglect their health, increasing their risk of development or progression of other disorders (eg, COPD). Depression may reduce protective immune responses. Depression increases risk of MIs and stroke because cytokines and factors that increase blood clotting are released during depression.
Major depression (unipolar disorder):Periods (episodes) that include ≥ 5 mental or physical symptoms and last ≥ 2 wk are classified as major depression. Symptoms must include sadness deep enough to be described as despondency or despair (often called depressed mood) or loss of interest or pleasure in usual activities (anhedonia). Other mental symptoms include feelings of worthlessness or guilt, recurrent thoughts of death or suicide, reduced ability to concentrate, and occasionally agitation. Physical symptoms include changes in weight or appetite, loss of energy, fatigue, psychomotor retardation or agitation, and sleep disorders (insomnia, hypersomnia, early morning awakening). Patients may appear miserable, with tearful eyes, furrowed brows, down-turned corners of the mouth, slumped posture, poor eye contact, lack of facial expression, little body movement, and speech changes (eg, soft voice, lack of prosody, use of monosyllabic words). The appearance may be confused with Parkinson's disease. In some patients, depressed mood is so deep that tears dry up; they report that they are unable to experience usual emotions and feel that the world has become colorless and lifeless. Nutrition may be severely impaired, requiring immediate intervention. Some depressed patients neglect personal hygiene or even their children, other loved ones, or pets.
Major depression is often divided into subgroups.
The psychotic subgroup is characterized by delusions, often of having committed unpardonable sins or crimes, harboring incurable or shameful disorders, or of being persecuted. Patients may have auditory or visual hallucinations (eg, accusatory or condemning voices).
The catatonic subgroup is characterized by severe psychomotor retardation or excessive purposeless activity, withdrawal, and, in some patients, grimacing and mimicry of speech (echolalia) or movement (echopraxia).
The melancholic subgroup is characterized by loss of pleasure in nearly all activities, inability to respond to pleasurable stimuli, unchanging emotional expression, excessive or inappropriate guilt, early morning awakening, marked psychomotor retardation or agitation, and significant anorexia or weight loss.
The atypical subgroup is characterized by a brightened mood in response to positive events and rejection sensitivity, resulting in depressed overreaction to perceived criticism or rejection, feelings of leaden paralysis or anergy, weight gain or increased appetite, and hypersomnia
Dysthymia: Low-level or subthreshold depressive symptoms are classified as dysthymia. Symptoms typically begin insidiously during adolescence and follow a low-grade course over many years or decades (diagnosis requires a course of ≥ 2 yr); dysthymia may intermittently be complicated by episodes of major depression. Affected patients are habitually gloomy, pessimistic, humorless, passive, lethargic, introverted, hypercritical of self and others, and complaining.
Depression not otherwise specified (NOS): Clusters of symptoms that do not meet criteria for other depressive disorders are classified as depression NOS. For example, minor depressive disorder may involve ≥ 2 wk of any of the symptoms of major depression but fewer than the 5 required for diagnosing major depression. Brief depressive disorder involves the same symptoms required for diagnosing major depression but lasts only 2 days to 2 wk. Premenstrual dysphoric syndrome involves a depressed mood, anxiety, and decreased interest in activities but only during most menstrual cycles, beginning in the luteal phase and ending within a few days after onset of menses
Mixed anxiety-depression: Although not considered a type of depression in DSM-IV, this condition, also called anxious depression, refers to concurrent mild symptoms common to anxiety and depression. The course is usually chronically intermittent. Because depressive disorders are more serious, patients with mixed anxiety-depression should be treated for depression. Obsessions, panic, and social phobias with hypersomniac depression suggest bipolar II disorder.
Diagnosis
Diagnosis is based on identifying the symptoms and signs described above. Several brief questionnaires are available for screening. They help elicit some depressive symptoms but cannot be used alone for diagnosis. Specific close-ended questions help determine whether patients have symptoms required by DSM-IV criteria for diagnosis of major depression.
Severity is assigned by the degree of pain and disability (physical, social, and occupational); duration of symptoms also helps determine severity. The presence of suicidal risk (manifested as suicidal ideas, plans, or attempts—see Suicidal Behavior) indicates that the disorder is severe. A physician should gently but directly ask patients about any thoughts and plans to harm themselves or others. Psychosis and catatonia indicate severe depression. Melancholic features indicate severe or moderate depression. Coexisting physical conditions, substance abuse disorders, and anxiety disorders may add to severity.
No laboratory findings are pathognomonic for depressive disorders. Tests for limbic-diencephalic dysfunction are rarely indicated or helpful. They include the thyrotropin-releasing hormone stimulation test, dexamethasone
suppression test, and sleep EEG for rapid eye movement latency, which is sometimes abnormal in depressive disorders. Sensitivity of these tests is low; specificity is better. PET scanning may show a decrease in brain metabolism of glucose in the dorsal frontal lobes and an increase in metabolism in the amygdala, cingulate, and subgenual cortex (all moderators of anxiety); these changes normalize with successful treatment.
Laboratory testing is necessary to exclude physical conditions that can cause depression. Tests include CBC, thyroid-stimulating hormone levels, and routine electrolyte, vitamin B12, and folate levels. Testing for illicit drug use is sometimes appropriate.
Depressive disorders must be distinguished from demoralization. Other mental disorders (eg, anxiety disorders) can mimic or obscure the diagnosis of depression. Sometimes more than one disorder is present. Major depression (unipolar disorder) must be distinguished from bipolar disorder (see Mood Disorders: Bipolar Disorders.
In elderly patients, depression can manifest as dementia of depression (formerly called pseudodementia), which causes many of the symptoms and signs of dementia— psychomotor retardation and decreased concentration (see Delirium and Dementia: Dementia.. However, early dementia may cause depression. In general, when the diagnosis is uncertain, treatment of a depressive disorder should be tried.
Differentiating chronic depressive disorders, such as dysthymia, from substance abuse disorders may be difficult, particularly because they can coexist and may contribute to each other.
Physical disorders must also be excluded as a cause of depressive symptoms. Hypothyroidism often causes symptoms of depression and is common, particularly among the elderly. Parkinson's disease, in particular, may manifest with symptoms that mimic depression (eg, loss of energy, lack of expression, paucity of movement). A thorough neurologic examination is needed to exclude this disorder.
Prognosis and Treatment
With treatment, symptoms often remit. Mild depression may be treated with general support and psychotherapy. Moderate to severe depression is treated with drugs, psychotherapy, or both, and sometimes electroconvulsive therapy. Some patients require > 1 drug or a combination of drugs. Improvement may require 1 to 4 wk of taking drugs as prescribed. Depression, especially in patients who have had > 1 episode, is likely to recur; therefore, severe cases often warrant long-term maintenance drug therapy.
Most people with depression are treated as outpatients. Patients with significant suicidal ideation, particularly when family support is lacking, require hospitalization, as do those with psychotic symptoms or physical debilitation.
Depressive symptoms in patients with substance abuse disorders often resolve within a few months of cessation of substance use. If a physical disorder or drug toxicity could be the cause, treatment is directed first at the disorder. If the diagnosis is in doubt or if symptoms are disabling or include suicidal ideation or hopelessness, a therapeutic trial with an antidepressant or a mood-stabilizing drug may help.
Initial support: A physician should see patients weekly or biweekly to provide support and education and to monitor progress. Telephone calls may supplement office visits. Patients and loved ones may be worried or embarrassed about the idea of having a mental disorder. The physician can help by explaining that depression is a serious medical disorder caused by biologic disturbances and requiring specific treatment and that depression is most often self-limiting and the prognosis with treatment is good. Patients and loved ones should be reassured that depression does not reflect a character flaw (eg, laziness). Telling patients that the path to recovery often fluctuates helps them put feelings of hopelessness in perspective and improves compliance.
Encouraging patients to gradually increase simple activities (eg, taking walks, exercising regularly) and social interactions must be balanced with acknowledging their desire to avoid activities. The physician can suggest that patients avoid self-blame and explain that dark thoughts are part of the disorder and will go away.
More: Depressive Disorders: Mood Disorders: Merck Manual Professional
The Merck Manuals, Online Medical Library
Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and sometimes by decreased interest or pleasure in activities. Exact cause is unknown but probably involves heredity, changes in neurotransmitter levels, altered neuroendocrine function, and psychosocial factors. Diagnosis is based on history. Treatment usually consists of drugs, psychotherapy, or both, and sometimes electroconvulsive therapy.
The term depression is often used to refer to any of several depressive disorders. Three are classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) by specific symptoms: major depressive disorder (often called major depression), dysthymia, and depressive disorder not otherwise specified. Two others are classified by etiology: depressive disorder due to a general physical condition and substance-induced depressive disorder.
Depressive disorders occur at any age but typically develop during the mid teens, 20s, or 30s. In primary care settings, as many as 30% of patients report depressive symptoms, but < 10% have major depression.
The term depression is often used to describe the low or discouraged mood that results from disappointments or losses. However, a better term for such a mood is demoralization. The negative feelings of demoralization, unlike those of depression, resolve when circumstances or events improve; the low mood usually lasts days rather than weeks or months, and suicidal thoughts and prolonged loss of function are much less likely.
Etiology
Exact cause is unknown. Heredity has an uncertain role; depression is more common among 1st-degree relatives of depressed patients, and concordance between identical twins is high. Hereditary genetic polymorphisms for the serotonin transporter active in the brain may be triggered by stress. People who have a history of child abuse or other major life stresses and have the short allele for this transporter are about twice as likely to develop depression as those who have the long allele.
Other theories focus on changes in neurotransmitter levels, including abnormal regulation of cholinergic, catecholaminergic (noradrenergic or dopaminergic), and serotonergic (5-hydroxytryptamine) neurotransmission. Neuroendocrine deregulation may be a factor, with particular emphasis on 3 axes: hypothalamic-pituitary-adrenal, hypothalamic-pituitary-thyroid, and growth hormone.
Psychosocial factors also seem involved. Major life stresses, especially separations and losses, commonly precede episodes of major depression; however, such events do not usually cause lasting, severe depression except in people predisposed to a mood disorder.
People who have had an episode of major depression are at higher risk of subsequent episodes. People who are introverted and who have anxious tendencies may be more likely to develop a depressive disorder. Such people often lack the social skills to adjust to life pressures. Depression may also develop in people with other mental disorders.
Women are at higher risk, but no theory explains why. Possible factors include greater exposure to or heightened response to daily stresses, higher levels of monoamine oxidase (the enzyme that degrades neurotransmitters considered important for mood), and endocrine changes that occur with menstruation and at menopause. In postpartum depression (see Postpartum Care: Mental Disorders.), symptoms develop within 4 wk after delivery; endocrine changes have been implicated, but the specific cause is unknown. Also, thyroid function is more commonly dysregulated in women.
In seasonal affective disorder, symptoms develop in a seasonal pattern, typically during autumn or winter; the disorder tends to occur in climates with long or severe winters. Depressive symptoms or disorders may occur with various physical disorders, including thyroid and adrenal gland disorders, benign and malignant brain tumors, stroke, AIDS, Parkinson's disease, and multiple sclerosis (see Table 1: Mood Disorders: Some Causes of Symptoms of Depression and Mania) Certain drugs, such as corticosteroids, some β-blockers, antipsychotics (especially in the elderly), and reserpine, can also result in depressive disorders. Abuse of some recreational drugs (eg, alcohol, amphetamines) can lead to or accompany depression. Toxic effects or withdrawal of drugs may cause transient depressive symptoms.
Symptoms and Signs
Depression causes cognitive, psychomotor, and other types of dysfunction (eg, poor concentration, fatigue, loss of sexual desire, menstrual abnormalities) as well as a depressed mood. Other mental symptoms or disorders (eg, anxiety and panic attacks) commonly coexist, sometimes complicating diagnosis and treatment. Patients with all forms of depression are more likely to abuse alcohol or other recreational drugs in an attempt to self-treat sleep disturbances or anxiety symptoms; however, depression is a less common cause of alcoholism and drug abuse than was once thought. Patients are also more likely to become heavy smokers and to neglect their health, increasing their risk of development or progression of other disorders (eg, COPD). Depression may reduce protective immune responses. Depression increases risk of MIs and stroke because cytokines and factors that increase blood clotting are released during depression.
Major depression (unipolar disorder):Periods (episodes) that include ≥ 5 mental or physical symptoms and last ≥ 2 wk are classified as major depression. Symptoms must include sadness deep enough to be described as despondency or despair (often called depressed mood) or loss of interest or pleasure in usual activities (anhedonia). Other mental symptoms include feelings of worthlessness or guilt, recurrent thoughts of death or suicide, reduced ability to concentrate, and occasionally agitation. Physical symptoms include changes in weight or appetite, loss of energy, fatigue, psychomotor retardation or agitation, and sleep disorders (insomnia, hypersomnia, early morning awakening). Patients may appear miserable, with tearful eyes, furrowed brows, down-turned corners of the mouth, slumped posture, poor eye contact, lack of facial expression, little body movement, and speech changes (eg, soft voice, lack of prosody, use of monosyllabic words). The appearance may be confused with Parkinson's disease. In some patients, depressed mood is so deep that tears dry up; they report that they are unable to experience usual emotions and feel that the world has become colorless and lifeless. Nutrition may be severely impaired, requiring immediate intervention. Some depressed patients neglect personal hygiene or even their children, other loved ones, or pets.
Major depression is often divided into subgroups.
The psychotic subgroup is characterized by delusions, often of having committed unpardonable sins or crimes, harboring incurable or shameful disorders, or of being persecuted. Patients may have auditory or visual hallucinations (eg, accusatory or condemning voices).
The catatonic subgroup is characterized by severe psychomotor retardation or excessive purposeless activity, withdrawal, and, in some patients, grimacing and mimicry of speech (echolalia) or movement (echopraxia).
The melancholic subgroup is characterized by loss of pleasure in nearly all activities, inability to respond to pleasurable stimuli, unchanging emotional expression, excessive or inappropriate guilt, early morning awakening, marked psychomotor retardation or agitation, and significant anorexia or weight loss.
The atypical subgroup is characterized by a brightened mood in response to positive events and rejection sensitivity, resulting in depressed overreaction to perceived criticism or rejection, feelings of leaden paralysis or anergy, weight gain or increased appetite, and hypersomnia
Dysthymia: Low-level or subthreshold depressive symptoms are classified as dysthymia. Symptoms typically begin insidiously during adolescence and follow a low-grade course over many years or decades (diagnosis requires a course of ≥ 2 yr); dysthymia may intermittently be complicated by episodes of major depression. Affected patients are habitually gloomy, pessimistic, humorless, passive, lethargic, introverted, hypercritical of self and others, and complaining.
Depression not otherwise specified (NOS): Clusters of symptoms that do not meet criteria for other depressive disorders are classified as depression NOS. For example, minor depressive disorder may involve ≥ 2 wk of any of the symptoms of major depression but fewer than the 5 required for diagnosing major depression. Brief depressive disorder involves the same symptoms required for diagnosing major depression but lasts only 2 days to 2 wk. Premenstrual dysphoric syndrome involves a depressed mood, anxiety, and decreased interest in activities but only during most menstrual cycles, beginning in the luteal phase and ending within a few days after onset of menses
Mixed anxiety-depression: Although not considered a type of depression in DSM-IV, this condition, also called anxious depression, refers to concurrent mild symptoms common to anxiety and depression. The course is usually chronically intermittent. Because depressive disorders are more serious, patients with mixed anxiety-depression should be treated for depression. Obsessions, panic, and social phobias with hypersomniac depression suggest bipolar II disorder.
Diagnosis
Diagnosis is based on identifying the symptoms and signs described above. Several brief questionnaires are available for screening. They help elicit some depressive symptoms but cannot be used alone for diagnosis. Specific close-ended questions help determine whether patients have symptoms required by DSM-IV criteria for diagnosis of major depression.
Severity is assigned by the degree of pain and disability (physical, social, and occupational); duration of symptoms also helps determine severity. The presence of suicidal risk (manifested as suicidal ideas, plans, or attempts—see Suicidal Behavior) indicates that the disorder is severe. A physician should gently but directly ask patients about any thoughts and plans to harm themselves or others. Psychosis and catatonia indicate severe depression. Melancholic features indicate severe or moderate depression. Coexisting physical conditions, substance abuse disorders, and anxiety disorders may add to severity.
No laboratory findings are pathognomonic for depressive disorders. Tests for limbic-diencephalic dysfunction are rarely indicated or helpful. They include the thyrotropin-releasing hormone stimulation test, dexamethasone
suppression test, and sleep EEG for rapid eye movement latency, which is sometimes abnormal in depressive disorders. Sensitivity of these tests is low; specificity is better. PET scanning may show a decrease in brain metabolism of glucose in the dorsal frontal lobes and an increase in metabolism in the amygdala, cingulate, and subgenual cortex (all moderators of anxiety); these changes normalize with successful treatment.
Laboratory testing is necessary to exclude physical conditions that can cause depression. Tests include CBC, thyroid-stimulating hormone levels, and routine electrolyte, vitamin B12, and folate levels. Testing for illicit drug use is sometimes appropriate.
Depressive disorders must be distinguished from demoralization. Other mental disorders (eg, anxiety disorders) can mimic or obscure the diagnosis of depression. Sometimes more than one disorder is present. Major depression (unipolar disorder) must be distinguished from bipolar disorder (see Mood Disorders: Bipolar Disorders.
In elderly patients, depression can manifest as dementia of depression (formerly called pseudodementia), which causes many of the symptoms and signs of dementia— psychomotor retardation and decreased concentration (see Delirium and Dementia: Dementia.. However, early dementia may cause depression. In general, when the diagnosis is uncertain, treatment of a depressive disorder should be tried.
Differentiating chronic depressive disorders, such as dysthymia, from substance abuse disorders may be difficult, particularly because they can coexist and may contribute to each other.
Physical disorders must also be excluded as a cause of depressive symptoms. Hypothyroidism often causes symptoms of depression and is common, particularly among the elderly. Parkinson's disease, in particular, may manifest with symptoms that mimic depression (eg, loss of energy, lack of expression, paucity of movement). A thorough neurologic examination is needed to exclude this disorder.
Prognosis and Treatment
With treatment, symptoms often remit. Mild depression may be treated with general support and psychotherapy. Moderate to severe depression is treated with drugs, psychotherapy, or both, and sometimes electroconvulsive therapy. Some patients require > 1 drug or a combination of drugs. Improvement may require 1 to 4 wk of taking drugs as prescribed. Depression, especially in patients who have had > 1 episode, is likely to recur; therefore, severe cases often warrant long-term maintenance drug therapy.
Most people with depression are treated as outpatients. Patients with significant suicidal ideation, particularly when family support is lacking, require hospitalization, as do those with psychotic symptoms or physical debilitation.
Depressive symptoms in patients with substance abuse disorders often resolve within a few months of cessation of substance use. If a physical disorder or drug toxicity could be the cause, treatment is directed first at the disorder. If the diagnosis is in doubt or if symptoms are disabling or include suicidal ideation or hopelessness, a therapeutic trial with an antidepressant or a mood-stabilizing drug may help.
Initial support: A physician should see patients weekly or biweekly to provide support and education and to monitor progress. Telephone calls may supplement office visits. Patients and loved ones may be worried or embarrassed about the idea of having a mental disorder. The physician can help by explaining that depression is a serious medical disorder caused by biologic disturbances and requiring specific treatment and that depression is most often self-limiting and the prognosis with treatment is good. Patients and loved ones should be reassured that depression does not reflect a character flaw (eg, laziness). Telling patients that the path to recovery often fluctuates helps them put feelings of hopelessness in perspective and improves compliance.
Encouraging patients to gradually increase simple activities (eg, taking walks, exercising regularly) and social interactions must be balanced with acknowledging their desire to avoid activities. The physician can suggest that patients avoid self-blame and explain that dark thoughts are part of the disorder and will go away.
More: Depressive Disorders: Mood Disorders: Merck Manual Professional
