Depression
Introduction
Background
Major depression, also known as unipolar depression, is one of
the more commonly encountered psychiatric disorders. While many
effective treatments are available, this disorder is often
underdiagnosed and undertreated. Primary care providers should
strongly consider the presence of depression in their patients;
studies suggest a high prevalence of affective disorders among
patients seeking medical attention in the office setting. Following
is a case study.
A 30-year-old presented to her primary care doctor with symptoms
of frequent headaches, insomnia, feeling overwhelmed, and have low
energy. Examination was unremarkable and blood workup supported
mild iron deficiency anemia. She returned after one month with
improvement in anemia but worsening of symptoms stated earlier.
APhysician Depression Questionaire (PDQ-9) revealed that for
several weeks she was feeling sad and had little interest or
pleasure in doing thing she used to enjoy. She also had suicidal
thoughts occasionally andcould not concentrate on tasks. She felt
like a failure. There were no recognizable losses. She stated that
in the pastshe had similar feelings, butthey were less intense and
lasted for shorter periods. She did not have any period of euphoria
or overproductiviy. Her primary care physician prescribed
antidepressants and referred her to a psychiatrist.
Pathophysiology
The underlying pathophysiology of major depressive disorder
(MDD) has not been clearly defined. Clinical and preclinical trials
suggest a disturbance in CNS serotonin (ie, 5-HT) activity as an
important factor. Other neurotransmitters implicated include
norepinephrine (NE) and dopamine (DA).1
The role of CNS serotonin activity in the pathophysiology of
major depressive disorder is suggested by the efficacy of selective
serotonin reuptake inhibitors (SSRIs) in the treatment of major
depressive disorder. Furthermore, studies have shown that an acute,
transient relapse of depressive symptoms can be produced in
research subjects in remission using tryptophan depletion, which
causes a temporary reduction in CNS serotonin levels. Serotonergic
neurons implicated in affective disorders are found in the dorsal
raphe nucleus, the limbic system, and the left prefrontal
cortex.
Clinical experience indicates a complex interaction between
neurotransmitter availability, receptor regulation and sensitivity,
and affective symptoms in major depressive disorder. Drugs that
produce only an acute rise in neurotransmitter availability, such
as cocaine, do not have the efficacy over time that antidepressants
do. Furthermore, an exposure of several weeks' duration to an
antidepressant is usuallynecessary to produce a change in symptoms.
This, together with preclinical research findings, implies a role
for neuronal receptor regulation over time in response to enhanced
neurotransmitter availability.
All available antidepressants appear to work via 1 or more of
the following mechanisms: (1) presynaptic inhibition of uptake of
5-HT or NE; (2) antagonist activity at presynaptic inhibitory 5-HT
or NE receptor sites, thereby enhancing neurotransmitter release;
or (3) inhibition of monoamine oxidase, thereby reducing
neurotransmitter breakdown.2 Frequency
United States
Lifetime incidence of major depressive disorder is 20% in women
and 12% in men. Prevalence is as high as 10% in patients observed
in a medical setting.
International
Cultural influences on the presentation of depression can be
significant. The practitioner should be aware of differences in the
expression of psychological distress in patients from other
countries or cultures. Some cultural patterns are mentioned in the
Diagnostic and Statistical Manual of Mental Disorders, Fourth
Edition, Text Revision (DSM-IV-TR); for example,major depressive
disorder may be expressed as fatigue, imbalance, or neurasthenia in
patients of Asian origin.
Mortality/Morbidity
Major depressive disorder is a disorder with significant
potential morbidity and mortality, contributing as it does to
suicide, medical illness, disruption in interpersonal
relationships, substance abuse, and lost work time.
Suicide ranks as a leading cause of death in the United States,
with a yearly rate of approximately 200,000 attempts. The number of
completed suicides for2005 was 32,000.
Suicide continues to rank as the second leading cause of death
in adolescents and represents 10-30% of deaths in those aged 20-35
years.Major depressive disorderplays a role in more than one half
of all suicide attempts, while the death rate from suicide among
those with affective disorders can exceed 15%. Firearms are the
most frequent method used in completed suicides. Risk factors for
suicide include (1) male sex; (2) age older than 55 years; (3)
concurrent chronic medical illness; (4) social isolation (eg,
divorced, widowed); (5) depression, especially with severe
melancholic or delusional symptoms; (6) substance abuse or
dependence; (7) family history of suicide and/or major depressive
disorder; (8) command hallucinations; (9) access to firearms; and
(10) white race.
Studies also show that major depressive disorder contributes to
higher mortality and morbidity in the context of other medical
illnesses, such as myocardial infarction, and that successful
treatment of the depressive episode improves medical and surgical
outcomes.
Race
Depression is less common in the black population.
Sex
Major depressive disorder is diagnosed more commonly in women,
with a prevalence twice that observed in men. In prepubertal
children, boys and girls are affected equally.
Age
The incidence of clinically significant depressive symptoms
increases with advancing age, especially when associated with
medical illness or institutionalization. However, depression might
not meet criteria for major depression because of somewhat atypical
features of depression in elderly persons. Elderly persons
experience more somatic complaints, cognitive symptoms, and fewer
complaints of sad or dysphoric mood. Of particular importance is
the increasing risk of death by suicide, particularly among elderly
men. Rates in women and men are highest in those aged 25-44 years.
For more information about childhood depression, see Mood Disorder:
Depression.
Clinical
History
The DSM-IV-TR diagnostic criteria for a major depressive episode
are as follows:
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Table
A. At least 5 of the following, during the same 2-week period,
representing a change from previous functioning; must include
either (a) or (b):
(a) Depressed mood(b) Diminished interest or pleasure(c)
Significant weight loss or gain(d) Insomnia or hypersomnia(e)
Psychomotor agitation or retardation(f) Fatigue or loss of
energy(g) Feelings of worthlessness(h) Diminished ability to think
or concentrate; indecisiveness(i) Recurrent thoughts of death,
suicidal ideation, suicide attempt, or specific plan for
suicide
B. Symptoms do not meet criteria for a mixed episode (ie, meets
criteria for both manic and depressive episode).
C. Symptoms cause clinically significant distress or impairment
of functioning.
D. Symptoms are not due to the direct physiologic effects of a
substance or a general medical condition.
E. Symptoms are not better accounted for by bereavement, ie, the
symptoms persist for longer than 2 months or are characterized by
marked functional impairment, morbid preoccupation with
worthlessness, suicidal ideation, psychotic symptoms, or
psychomotor retardation.
A. At least 5 of the following, during the same 2-week period,
representing a change from previous functioning; must include
either (a) or (b):
(a) Depressed mood(b) Diminished interest or pleasure(c)
Significant weight loss or gain(d) Insomnia or hypersomnia(e)
Psychomotor agitation or retardation(f) Fatigue or loss of
energy(g) Feelings of worthlessness(h) Diminished ability to think
or concentrate; indecisiveness(i) Recurrent thoughts of death,
suicidal ideation, suicide attempt, or specific plan for
suicide
B. Symptoms do not meet criteria for a mixed episode (ie, meets
criteria for both manic and depressive episode).
C. Symptoms cause clinically significant distress or impairment
of functioning.
D. Symptoms are not due to the direct physiologic effects of a
substance or a general medical condition.
E. Symptoms are not better accounted for by bereavement, ie, the
symptoms persist for longer than 2 months or are characterized by
marked functional impairment, morbid preoccupation with
worthlessness, suicidal ideation, psychotic symptoms, or
psychomotor retardation.
Atypical presentations
Patients with major depressive disorder may not initially
present with a complaint of low mood, anhedonia, or other typical
symptoms.
In the primary care setting, where many of these patients first
seek treatment, the presenting complaints often can be somatic,
such as fatigue, headache, abdominal distress, or change in weight.
Patients may complain more of irritability than of sadness or low
mood.
Elderly persons may present with confusion or a general decline
in functioning.
Children with major depressive disorder may also present with
initially misleading symptoms such as irritability, decline in
school performance, or social withdrawal. Depression can occur in
preschool children.3 Ren Spitz described what he called anaclitic
depression in infants being raised in an orphanage.4 Childhood
depression seems to be a more severe form of the same disorder in
adults. Evidence-based treatment guidelines are limited. Of
teenagers diagnosed with major depressive disorder, bipolar
disorder is diagnosed in 50% of them as they grow into adulthood.
Further research is needed in this area.
The differential diagnosis in patients presenting with
alterations in mood is extensive and should include consideration
of the following:
Mood disorders secondary to CNS conditions: These include a
broad range of physiologic and structural CNS processes that can
produce changes in mood and behavior. Note that major depressive
disorder can produce measurable cognitive deficits or a worsening
of preexisting dementia. This decline in cognitive functioning,
which, on formal testing, appears to arise from impaired
concentration or motivation, is referred to as pseudodementia or,
more currently, as dementia of depression and should remit with
successful treatment of the depressive episode. Major depressive
disorder does not cause focal neurologic signs. Such findings
should prompt an evaluation for other organic syndromes.
Alzheimer disease: This disease and other degenerative and
vascular dementias can be associated with affective symptoms. Mood
disorders are very prominent in Parkinson disease, Huntington
disease, multiple sclerosis, stroke, and seizure disorders.
Neoplastic lesions of the CNS: These lesions also can cause
changes in mood and behavior before the onset of focal neurologic
signs.
Inflammatory conditions: Conditions such as systemic lupus
erythematosus (SLE) can produce a wide range of neuropsychiatric
signs and symptoms, likely because of alterations in the
blood-brain barrier and an autoimmune cerebritis.
Sleep disorders: Obstructive sleep apnea, especially, can cause
significant medical and psychiatric symptoms and often is missed as
a diagnosis. Patients, and, if necessary, their partners, should be
interviewed regarding their sleep quality, daytime sleepiness, and
snoring. Polysomnography can help make the diagnosis and guide
treatment.
Infectious processes: These include syphilis, Lyme disease, and
HIV encephalopathy, which can cause mood and behavior changes.
Pharmacologic agents: Substances that can produce changes in
mood include antihypertensive medications (especially
beta-blockers, reserpine, methyldopa, and calcium channel
blockers); steroids; medications that affect sex hormones (eg,
estrogen, progesterone, testosterone, gonadotropin-releasing
hormone [GnRH] antagonists); H2 blockers (eg, ranitidine,
cimetidine); sedatives; muscle relaxants; appetite suppressants;
and chemotherapy agents (eg, vincristine, procarbazine,
L-asparaginase, interferon, amphotericin B, vinblastine).
Endocrinologic disorders: Disorders involving the
hypothalamic-pituitary-adrenal axis or thyroid are especially
likely to produce changes in mood. These include Addison disease,
Cushing disease, hyperthyroidism, hypothyroidism, prolactinomas,
and hyperparathyroidism.
Substance use, abuse, or dependence: These can cause significant
mood symptoms. This is especially true of alcohol, cocaine,
amphetamines, marijuana, sedatives/hypnotics, and narcotics.
Inhalant abuse also should be considered, particularly among young
male patients. Other substance-related and psychiatric processes
either can present with mood disturbance as the primary symptom or
can occur together with major depressive disorder.
Axis I or II disorder: In cases in which another Axis I or II
disorder is present, a careful psychiatric review of systems should
elicit the alternative or additional diagnosis.
Seasonal affective disorder: Also known as SAD, this form of
major depressive disorder shows a seasonal pattern of exacerbation
and remission. SAD usually is treated with bright light therapy
(BLT), with or without antidepressant medication.
Dysthymia: This mood disorder presents with low mood as a
primary symptom. Dysthymia can predate a depressive episode. The
symptoms of dysthymia alone do not meet criteria for major
depressive disorder and must be present for at least 2 years.
Anxiety disorders: Patients with anxiety disorders are at higher
risk for developing comorbid depression. In such patients, it is
important to identify the anxiety disorder because they often
require specific treatment approaches. Commonly encountered anxiety
disorders include panic disorder, obsessive-compulsive disorder,
generalized anxiety disorder, posttraumatic stress disorder, and
phobia.
Eating disorders: People with eating disorders (EDs) also have a
high rate of comorbid major depressive disorder and require
specific treatment approaches. These disorders include bulimia,
anorexia nervosa, and ED not otherwise specified. A large
percentage of individuals in this last group have binge-eating
disorder (BED), which, while not currently listed in the DSM-IV-TR
as a specific diagnosis, constitutes most patients with EDs.
Personality disorders: Certain personality disorders (eg,
borderline personality disorder) may present with mood changes as a
prominent symptom. Remember that the presence of a personality
disorder can be difficult to determine in the setting of acute
affective symptoms. Many patients who are depressed who appear
labile, demanding, or pathologically dependent look dramatically
different once the depressive episode has been treated
adequately.
Physical
No physical findings are specific to major depressive disorder.
Diagnosis lies in the history and the mental status
examination.
Appearance and affect
Most patients with major depressive disorder present to their
physician with a normal appearance.
In patients with more severe symptoms, a decline in grooming and
hygiene can be observed, as well as a change in weight. Patients
may show psychomotor retardation, which is manifest as a slowing or
loss of spontaneous movement and reactivity. Together with this,
major depressive disorder often produces a flattening or loss of
reactivity in the patient's affect (ie, emotional expression).
Psychomotor agitation or restlessness also can be observed in
some patients with major depressive disorder.
Mood and thought process
Patients report a dysphoric mood state, which may be expressed
as sadness, heaviness, numbness, or sometimes irritability and mood
swings. They often report a loss of interest or pleasure in their
usual activities, difficulty concentrating, or loss of energy and
motivation. Their thinking often is negative, frequently with
feelings of worthlessness, hopelessness, or helplessness. While it
is not uncommon for patients with major depressive disorder to show
ruminative thinking, it is important to evaluate each patient for
evidence of psychotic symptoms because this affects initial
management.
Psychosis, when it occurs in the context of unipolar depression,
usually is congruent in its content with the patient's mood state;
for example, the patient may experience delusions of worthlessness
or some progressive physical decline. Symptoms of psychosis should
prompt a careful history evaluation to rule out a history of
bipolar disorder, schizophrenia or schizoaffective disorder,
substance abuse, or organic brain syndrome.
Cognition and sensorium: Patients with major depressive disorder
often complain of poor memory or concentration. Most commonly, no
significant deficits are found on cognitive examination. If
present, such findings may represent pseudodementia; however, they
may indicate an underlying dementia or other organic brain syndrome
and should be investigated. The level of consciousness (ie,
sensorium) should be normal. A fluctuating or depressed sensorium
suggests delirium, and the patient should be evaluated for organic
contributors.
Speech: Speech may be normal, slow, monotonic, or lacking in
spontaneity and content. Pressured speech should suggest mania,
while disorganized speech should prompt an evaluation for
psychosis. Racing thoughts could also be an indication of mania or
hypomania.
Thought content, suicidality, and homicidality
The thought content of patients who are depressed usually is
consistent with their dysphoric mood. Patients often report feeling
overwhelmed or inadequate, helpless, worthless, or hopeless.
Thought content always should be assessed for hopelessness,
suicidal ideation, or homicidal/violent ideation or intent.
A history of suicide attempts or violence is a significant risk
factor for future attempts, and this should be noted in the
history.
Hallucinations and delusions, including command
hallucinations,could be partof presentation. These are usually mood
congruent but could be mood incongruent.These psychotic elements,
especially command hallucinations,are associated with increased
suicidal and homicidal actions.
Depression screening tests such as PDQ-9 and Mood Disorder
Questionnaire (MDQ) could be used easily in a primary care setting
to screen for depression and bipolar disorder. The Hamilton and the
Beck Depression inventory could also besimilarly useful but are
more detailed and time consuming.
Causes
The specific cause of major depressive disorder is not known. As
with most psychiatric disorders, major depressive disorder appears
to be multifactorial in its origin.
Biological contributors
Genetic susceptibility plays a role in the development of major
depressive disorder. Individuals with a family history of affective
disorders (7%), panic disorder, and alcohol dependence (8%) carry a
higher risk for major depressive disorder.
Certain neurologic illnesses increase the risk of major
depressive disorder. Examples include Parkinson disease, stroke,
multiple sclerosis, and seizure disorders.
Exposure to certain pharmacologic agents also increases the
risk; medications such as reserpine or beta-blockers, as well as
abused substances such as cocaine, amphetamine, narcotics, and
alcohol are associated with higher rates of major depressive
disorder.
Chronic pain, medical illness, and psychosocial stress also can
play a role in both the initiation and maintenance of major
depressive disorder. The psychological component of these risk
factors is discussed below. However, neurochemical hypotheses point
to the deleterious effects of cortisol and other stress-related
substances on the neuronal substrate of mood in the CNS.
Psychosocial contributors: While major depressive disorder can
arise without any precipitating stressors, stress and interpersonal
losses certainly increase risk. Psychodynamic formulations find
that significant losses in early life predispose to major
depressive disorder over the lifespan of the individual, as does
trauma, either transient or chronic.
Exercise Prescription
Author: Amer Suleman, MD, Consultant in Electrophysiology and
Cardiovascular Medicine, Department of Internal Medicine, Division
of Cardiology, Medical City Dallas HospitalCoauthor(s): Kyle D
Heffner, MS, CPFT, CCT, Consultant, Frontera StrategiesContributor
Information and DisclosuresUpdated: Jun 24, 2009
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References
Further ReadingIntroduction
Substantial data are availableregarding the benefits of physical
activity.1,2,3,4,5,6,7 For primary preventative benefits, physical
activity patterns should begin in the early school years and
continue throughout an individual's life. Schools must specifically
designate physical education programs with aerobic activities for
children at early ages. Programs should include recreational sports
(eg, running, dancing, swimming). Support at home for an active
lifestyle for children helps to promote healthy physical activity
patterns.
In the clinical setting, discuss physical activity and provide
exercise prescriptions for patients and their families. In some
instances, suggestions could be made about implementing physical
activity recommendations at the work site.
Consider intensity, duration, frequency, mode, and progression
in all types of physical activity programs. As children and
adolescents become adults and discontinue the athletic endeavors of
school and college, primary prevention must include a plan for a
lifetime of appropriate physical activity. Ideally, this activity
should be performed for at least 30-60 minutes, 4-6 times weekly or
30 minutes on most days of the week. The frequency, duration, and
intensity of activity should be individualized (exercise
prescription) to personal satisfaction, mode, and progression.
Subjects may use individual end points of exercise, such as
breathlessness and/or a fatigue level ranging from somewhat hard to
hard on the Borg perceived exertion scale (see Glossary of
Terms,Borg rating of perceived exertion[RPE]). Standardized charts
that designate heart rates may help by providing heart rate end
points that can be measured immediately after exercise, but these
are not necessary. Exercise should include aerobic activities, such
as bicycling (stationary or routine), walk-jog protocols, swimming,
and other active recreational or leisure sports. Shoes and clothing
should be appropriate for extremes of heat, cold, and humidity.
Resistive exercises using free weights or standard equipment
should be performed 2-3 times per week. These exercises should
include 8-10 exercise sets that consist of 10-15 repetitions per
set (including arms, shoulders, chest, trunk, back, hips, and legs)
and are performed at a moderate intensity. If free weights are
used, 15-30 lb is generally adequate or resistance that requires a
perceived effort that is relatively hard (ie, an RPE
15-16).Resistive exercises tend to complement aerobic exercise in
that some training effect is realized.8 However, as adults age,
development of muscle tone and strengthening of body musculature is
more important.
The long-term effect of any physical activity program is
affected by compliance. In today's mobile society, an exercise plan
must include activities for business trips and vacations. Exercise
facilities may not be convenient in such settings, which may mean
improvising. For example, a walk-jogger should bring walking or
running shoes and find a safe place to walk or run at a pace that
approximates the usual activity level. Many hotels or motels have
exercise facilities with a track or treadmill, exercise cycle, and
weights, enabling travelers or others away from their usual routine
to maintain an exercise program.
Physical activity measured in total time or kilocalories (kcal)
or kilojoules (kJ) per week is appropriate and may be achieved with
various combinations of scheduling, such as 10-15 minutes in the
morning, at noon, and/or an afternoon/evening session. Many persons
may schedule longer, less frequent periods of exercise. As
intensity decreases, frequency and duration should increase and
vice versa. The dosage or total energy (calorie) expenditure per
week must be individualized (exercise prescription).
Persons with influenza syndromes or respiratory illnesses should
decrease or stop exercise until they have recovered. If the
recovery time is greater than 2-3 weeks, activity should be resumed
at a lower level to compensate for the slight loss in training
level.Maintenance of the cardiovascular training effects of
exercise has been shown to be more related to the exercise
intensity than to exercise frequency or duration. In other words,
if the intensity is maintained, even though the exercise sessions
are less frequent or shorter in duration, transient reductions in
conditioning from the decreased exercise appears to be
minimized.
Various exercise testing measures of functional capacity should
be used in special populations but are not necessary for primary
prevention. Traditionally, many athletically inclined persons like
to have periodic oxygen-uptake (VO2) measurements to assess their
level of training. However, recent technologic advances have not
only made cardiopulmonary (CPX) or metabolic (CMET) testing more
commonplace among medical practices,butthey have also become
increasingly popular as a part of a routine physical and stress
test evaluation, especially for individuals who are considered at
high risk for cardiovascular disease (eg, those with hypertension,
shortness of breath, chest discomfort, or abnormal blood lipid
levels).
A lifestyle of physical activity from childhood throughout the
adult years fosters health and longevity. Even brisk walking as a
physical activity/exercise habit promotes health benefits. This is
the simplest program for most individuals and has clear benefits.
This improved state of health is enhanced by weight control,
restricted intake of saturated fat and cholesterol, abstinence from
cigarette smoking, and control of high blood pressure and glucose
intolerance.
For excellent patient education resources, visit eMedicine's
Public Health Center. Also, see eMedicine's patient education
articles Walking for Fitness and Strength Training.
Benefits of Exercise
Routine exercise improves tissue VO2 affects the following:
Improves insulin sensitivity
Improves glycemic control in persons with type 2 diabetes (and,
hence, decreases overall mortality)9 Decreases blood pressure
Decreases low-density lipoprotein and triglyceride levels
Increases high-density lipoprotein levels
Considerable data also support evidence that exercise may
decrease the prevalence of colon cancer and endometrial cancer.
Exercise also helps with osteoarthritis and obesity, as well as
reportedly benefits persons with migraine headaches and
fibromyalgia.
Middle-aged men and women who work in physically demanding jobs
or perform moderate to strenuous recreational activities have fewer
manifestations of coronary artery disease than their less active
peers. Meta-analysis studies of clinical trials reveal that
medically prescribed and supervised exercise can reduce mortality
rates for persons with coronary artery
disease.1,7,10,11,12,13,14
In a meta-analysis of 33 studies that included almost 200,000
participants and cases, Kodama et al quantified the relationship
between better cardiorespiratory fitness and lower rates of
coronary heart disease (CHD) and cardiovascular disease (CVD)
events, as well as deaths from all causes.15 When cardiorespiratory
fitness was estimated as maximal aerobic capacity (MAC) expressed
in metabolic equivalent (MET) units, a MAC of 7.9 METs was
associated with substantially lower rates of CHD/CVD events and
all-cause mortality.15
Furthermore, categorization of cardiorespiratory fitness as low
(
