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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: Management in the Hospital), 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.
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Table 1
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Some Causes of Symptoms
of Depression and Mania
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Type of Disorder
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Depression
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Mania
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Connective tissue
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SLE
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Rheumatic fever
SLE
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Endocrine
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Addison's disease
Cushing's disease
Diabetes mellitus
Hyperparathyroidism
Hyperthyroidism and hypothyroidism
Hypopituitarism
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Hyperthyroidism
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Infectious
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AIDS
General paresis (parenchymatous neurosyphilis)
Influenza
Infectious mononucleosis
TB
Viral hepatitis
Viral pneumonia
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AIDS
General paresis
Influenza
St. Louis encephalitis
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Neoplastic
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Cancer of the head of the pancreas
Disseminated carcinomatosis
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Neurologic
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Cerebral tumors
Complex partial seizures (temporal lobe)
Head trauma
Multiple sclerosis
Parkinson's disease
Sleep apnea
Stroke (left frontal)
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Complex partial seizures (temporal lobe)
Diencephalic tumors
Head trauma
Huntington's disease
Multiple sclerosis
Stroke
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Nutritional
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Pellagra
Pernicious anemia
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Other*
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Coronary artery disease
Fibromyalgia
Renal or hepatic failure
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Pharmacologic
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Amphetamine withdrawal
Amphotericin B
Anticholinesterase insecticides
Barbiturates
Cimetidine
Corticosteroids
Cycloserine
Indomethacin
Mercury
Metoclopramide
Phenothiazines
Reserpine
Thallium
Vinblastine
Vincristine
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Amphetamines
Certain antidepressants
Bromocriptine
Cocaine
Corticosteroids
Levodopa
Methylphenidate
Sympathomimetic drugs
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Mental
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Alcoholism and other substance use disorders
Antisocial personality
Dementing disorders in the early phase
Schizophrenic disorders
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*Depression is highly associated with these disorders, but no causal relationship has been established.
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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. (See also the American Psychiatric Association's Guideline Watch: Practice Guideline
for the Treatment of Patients With Major Depressive Disorder, 2nd
Edition.)
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.
Psychotherapy:
Individual psychotherapy, often as cognitive-behavioral therapy (individual or group) alone is often effective for milder forms of depression. Cognitive-behavioral therapy is increasingly used to combat the inertia and self-defeating mental set of depressed patients. However, cognitive-behavioral therapy is most useful when used with antidepressants to treat moderate to severe depression. Cognitive-behavioral therapy may improve coping skills and enhance gains by providing support and guidance, by removing cognitive distortions that prevent adaptive action, and by encouraging the patient to gradually resume social and occupational roles. Couple therapy may help reduce conjugal tensions and disharmony. Long-term psychotherapy is unnecessary except for patients who have long-term interpersonal conflicts or who are unresponsive to brief therapy.
Selective serotonin
reuptake inhibitors (SSRIs):
These drugs prevent reuptake of serotonin (5-hydroxytryptamine [5-HT]). SSRIs include citalopram , escitalopram , fluoxetine , fluvoxamine , paroxetine , and sertraline . Although these drugs have the same mechanism of action, differences in their clinical properties make selection important. SSRIs have a wide therapeutic margin; they are relatively easy to administer, with little need for dose adjustment (except for fluvoxamine ).
By preventing reuptake of 5-HT presynaptically, SSRIs result in more 5-HT to stimulate postsynaptic 5-HT receptors. SSRIs are selective to the 5-HT system but not specific for the different 5-HT receptors. Thus, they stimulate 5-HT1 receptors, with antidepressant and anxiolytic effects, but they also stimulate 5-HT2, commonly causing anxiety, insomnia, and sexual dysfunction, and 5-HT3 receptors, commonly resulting in nausea and headache. Thus, SSRIs can paradoxically relieve and cause anxiety.
A few patients may seem more agitated, depressed, and anxious within a week of starting SSRIs or increasing the dose. Patients and their loved ones should be warned of this possibility and instructed to call the physician if symptoms worsen with treatment. This situation should be closely monitored because some patients, especially younger children and adolescents, become increasingly suicidal if agitation, increased depression, and anxiety are not detected and rapidly treated. Recent studies have determined that children and adolescents have an increased rate of suicidal ideation, suicide gestures, and suicide attempts during the first few months of taking SSRIs (the same concern may apply to serotonin modulators, serotonin- norepinephrine reuptake inhibitors, and dopamine - norepinephrine reuptake inhibitors); physicians must balance this risk with clinical need.
Sexual dysfunction (especially difficulty achieving orgasm but also decreased libido and erectile dysfunction) occurs in ≥ 1⁄3 of patients. Some SSRIs cause weight gain. Others, especially fluoxetine , cause anorexia in the first few months. SSRIs have few anticholinergic, adrenolytic, and cardiac conduction effects. Sedation is minimal or nonexistent, but in the early weeks of treatment, some patients tend to be sleepy during the day. Loose stools or diarrhea occurs in some patients.
Drug interactions are relatively uncommon; however, fluoxetine , paroxetine , and fluvoxamine can inhibit CYP450 isoenzymes, which can lead to serious drug interactions. For example, fluoxetine and fluvoxamine can inhibit the metabolism of certain β-blockers, including propranolol and metoprolol , potentially resulting in hypotension and bradycardia.
Serotonin
modulators (5-HT2 blockers):
These drugs block primarily the 5-HT2 receptor and inhibit reuptake of 5-HT and norepinephrine . Serotonin modulators include nefazodone , trazodone , and mirtazapine . Serotonin modulators have antidepressant and anxiolytic effects but do not cause sexual dysfunction. Unlike most antidepressants, nefazodone does not suppress REM sleep and produces restful sleep. Nefazodone can significantly interfere with drug-metabolizing liver enzymes and has been associated with liver failure.
Trazodone is related to nefazodone but does not inhibit 5-HT reuptake presynaptically. Unlike nefazodone , trazodone has caused priapism (in 1/1000) and, as an α1-noradrenergic blocker, may cause orthostatic (postural) hypotension. It is very sedating, so its use in antidepressant doses (> 200 mg/day) is limited. It is most often given in 50- to 100-mg doses at bedtime to depressed patients with insomnia.
Mirtazapine inhibits 5-HT reuptake and blocks α2-adrenergic autoreceptors as well as 5-HT2 and 5-HT3 receptors. The result is more efficient serotonergic function and increased noradrenergic function without sexual dysfunction or nausea. It has no cardiac adverse effects, has minimal interaction with drug-metabolizing liver enzymes, and is generally well tolerated, except for sedation and weight gain mediated by H1 (histamine) blockade.
Serotonin-norepinephrine reuptake inhibitors:
These drugs (eg, venlafaxine , duloxetine ) have a dual 5-HT and norepinephrine mechanism of action, as do tricyclic antidepressants. However, their toxicity approximates that of SSRIs; nausea is the most common problem during the first 2 wk. Venlafaxine has some potential advantages over SSRIs: It may work better in some patients with severe or refractory depression, and because it is not highly protein bound and has virtually no interaction with drug-metabolizing liver enzymes, it poses little risk when given with other drugs. However, withdrawal symptoms (irritability, anxiety, nausea) often occur if the drug is stopped suddenly. Duloxetine resembles venlafaxine in effectiveness and adverse effects.
Dopamine-norepinephrine
reuptake inhibitors:
By mechanisms not clearly understood, they favorably influence catecholaminergic, dopaminergic, and noradrenergic function. These drugs do not affect the 5-HT system.
Bupropion is currently the only drug in this class. It can help depressed patients with concurrent attention-deficit hyperactivity disorder or cocaine dependence and those trying to stop smoking. Bupropion causes hypertension in a very few patients but has no other effects on the cardiovascular system. Bupropion can cause seizures in 0.4% of patients taking doses > 150 mg tid (or > 200 mg sustained-release [SR] bid or > 450 mg extended-release [XR] once/day); risk is increased in patients with bulimia. Bupropion does not have sexual adverse effects and interacts little with coadministered drugs, although it does inhibit the CYP2D6 hepatic enzyme. Agitation, which is common, is considerably attenuated by using the sustained-release or extended-release form. Bupropion may result in dose-related recent memory loss that is reversible with dose reduction.
Heterocyclic antidepressants:
This group of drugs, once the mainstay of treatment, includes tricyclic (tertiary amines amitriptyline and imipramine and their secondary amine metabolites nortriptyline and desipramine ), modified tricyclic, and tetracyclic antidepressants. Acutely, these drugs increase the availability of primarily norepinephrine and, to some extent, 5-HT by blocking reuptake in the synaptic cleft. Long-term use downregulates α1-adrenergic receptors on the postsynaptic membrane—a possible final common pathway of their antidepressant activity. Although effective, these drugs are now rarely used because overdose causes toxicity and they have more adverse effects. The more common adverse effects of heterocyclics are due to their muscarinic-blocking, histamine-blocking, and α1-adrenolytic actions. Many heterocyclics have strong anticholinergic properties and are thus unsuitable for the elderly and for patients with benign prostatic hypertrophy, glaucoma, or chronic constipation. All heterocyclics, particularly maprotiline and clomipramine , lower the threshold for seizures.
Monoamine
oxidase inhibitors (MAOIs):
These drugs inhibit the oxidative deamination of the 3 classes of biogenic amines ( norepinephrine , dopamine , and 5-HT) and other phenylethylamines. MAOIs have little or no effect on normal mood. Their primary value is their effectiveness when other antidepressants are ineffective (eg, for atypical depression when SSRIs are ineffective).
MAOIs marketed as antidepressants in the US (eg, phenelzine , tranylcypromine , isocarboxazid ) are irreversible and nonselective (inhibiting MAO-A and MAO-B). They can cause hypertensive crises if a sympathomimetic drug or food containing tyramine or dopamine is ingested concurrently. This effect is called the cheese reaction because mature cheese has a high tyramine content. MAOIs are underused because of concern about this reaction. More selective and reversible MAOIs (eg, moclobemide , befloxatone), which inhibit MAO-A, are not yet available in the US; they are relatively free of these interactions. To prevent hypertension and febrile crises, patients taking MAOIs should avoid sympathomimetic drugs (eg, pseudoephedrine ), dextromethorphan , reserpine , and meperidine as well as malted beers, Chianti wines, sherry, liqueurs, and overripe, aged foods that contain tyramine or dopamine (eg, bananas, fava or broad beans, yeast extracts, canned figs, raisins, yogurt, cheese, sour cream, soy sauce, pickled herring, caviar, liver, extensively tenderized meats). Patients can carry 25-mg tablets of chlorpromazine and, as soon as signs of such a hypertensive reaction occur, take 1 or 2 tablets as they head for the nearest emergency department.
Common adverse effects include erectile dysfunction (least common with tranylcypromine ), anxiety, nausea, dizziness, insomnia, pedal edema, and weight gain. MAOIs should not be used with other classes of antidepressants, and at least 2 wk (5 wk with fluoxetine , which has a long half-life) should elapse between use of the 2 classes of drugs. MAOIs used with antidepressants that affect the 5-HT system (eg, SSRIs, nefazodone ) could cause a neuroleptic malignant syndrome (malignant hyperthermia, muscle breakdown, renal failure, seizures, and eventual death—see Approach to the Patient With Mental Complaints: Adverse effects of antipsychotic drugs). Patients who are taking MAOIs and who also need antiasthmatic, antiallergic, local anesthetic, or general anesthetics should be treated by a psychiatrist and an internist, a dentist, or an anesthesiologist with expertise in neuropsychopharmacology.
Drug
choice and administration:
Choice of drug may be guided by past response to a specific antidepressant. Otherwise, SSRIs are the starting drugs of choice. Although the different SSRIs are equally effective for typical cases, certain properties of the drugs make them more or less appropriate for certain patients (see
Table 2: Mood Disorders: Antidepressants ).
If one SSRI is ineffective, another SSRI can be substituted, but an antidepressant from a different class is more likely to help. Tranylcypromine in high doses (20 to 30 mg po bid) is often effective for depression refractory to sequential trials of other antidepressants; it should be given by a physician experienced in use of MAOIs. Psychologic support of patients and loved ones is particularly important in refractory cases.
Insomnia, a common adverse effect of SSRIs, is treated by reducing the dose or adding a low dose of trazodone or another sedating antidepressant. Initial nausea and loose stools usually resolve, but throbbing headaches do not always go away, necessitating a change in drug class. An SSRI should be stopped if it causes agitation (most common with fluoxetine ). When decreased libido, impotence, or anorgasmia occur during SSRI therapy, dose reduction may help, or a change can be made to another drug class.
SSRIs, which tend to stimulate many depressed patients, should be given in the morning. Giving the entire heterocyclic antidepressant dose at bedtime usually makes sedatives unnecessary, minimizes adverse effects during the day, and improves compliance. MAOIs are usually given in the morning and early afternoon to avoid excessive stimulation.
Therapeutic response with most classes of antidepressants usually occurs in about 2 to 3 wk (sometimes as early as 4 days or as late as 8 wk). For a first episode of mild or moderate depression, the antidepressant should be given for 6 mo, then tapered gradually over 2 mo. If the episode is severe or a recurrence or if there is suicidal risk, the dose that produces full remission should be continued during maintenance. For psychotic depression, maximal doses of a venlafaxine or a heterocyclic antidepressant (eg, nortriptyline ) can be given for 3 to 6 wk; if necessary, an antipsychotic (eg, risperidone starting at 0.5 to 1 mg po bid and titrated to 4 to 8 mg once/day, olanzapine starting at 5 mg po once/day and titrated to 10 to 20 mg once/day, quetiapine starting at 25 mg po bid and titrated to 200 to 375 mg po bid) can be added. To reduce risk of tardive dyskinesia, the physician should give the antipsychotic in the lowest effective dose and stop it as soon as possible.
Continued therapy with an antidepressant for 6 to 12 mo (up to 2 yr in patients > 50 yr) is usually needed to prevent relapse. Most antidepressants, especially SSRIs, should be tapered off (by decreasing the dose by about 25%/wk) rather than discontinued abruptly; stopping SSRIs abruptly may result in serotonergic syndrome (nausea, chills, muscles aches, dizziness, anxiety, irritability, insomnia, and fatigue).
Medicinal herbs are used by some patients. St. John's wort (see Dietary Supplements: St. John's Wort) may be effective for mild depression, although data are contradictory. St. John's wort may interact with other antidepressants.
Electroconvulsive
therapy (ECT):
Severe suicidal depression, depression with agitation or psychomotor retardation, or depression during pregnancy is often treated with ECT if drugs are ineffective. Patients who have stopped eating may need ECT to prevent death. ECT is also effective for psychotic depression. Response to 6 to 10 ECT treatments is usually dramatic and may be lifesaving. Relapse after ECT is common, and drug therapy is often maintained after ECT is stopped.
Phototherapy:
Phototherapy may be used in patients with seasonal depression. Treatment can be provided at home with 2,500 to 10,000 lux at a distance of 30 to 60 cm for 30 to 60 min/day (longer with a less intense light source). In patients who go to sleep late at night and rise late in the morning, phototherapy is most effective in the morning, sometimes supplemented with 5 to 10 min of exposure between 3 and 7 pm. For patients who go to sleep and rise early, phototherapy is most effective between 3 pm and 7 pm.
Last full review/revision November 2005
Content last modified November 2005
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