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Depression

Synonyms: major depressive disorder, MDD, unipolar depression, unipolar affective disorder.

INTRODUCTION

Background: 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.

Frequency:

In the US lifetime incidence of MDD is 20% in women and 12% in men. Prevalence is as high as
10% in patients observed in a medical setting.

Cultural influences on the presentation of depression can be significant in all countries. 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,
MDD may be expressed as fatigue, imbalance, or neurasthenia in patients of Asian origin.

Mortality/Morbidity: MDD 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 for 1998 was 30,575.
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. MDD plays 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) the first one is male sex (but MDD is diagnosed more commonly in women, with a
prevalence twice that observed in men);
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(2) age older than 55 years and concurrent chronic medical illness (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.
Studies also show that MDD 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);

(3) social isolation (eg, divorced, widowed);

(4) depression, especially with severe melancholic or delusional symptoms;

(5) substance abuse or dependence;

(6) family history of suicide and/or MDD;

(7) command hallucinations;

(8) access to firearms;

(9) white race.

CLINICAL

History: (слайд 2, 2 шт.) The DSM-IV diagnostic criteria for a major depressive episode are
as follows:

A. At least 5 of the following, during the same 2-week period, representing a change from
previous functioning; must include either depressed mood
or diminished interest or pleasure. These are the basic symptoms. But there are some
additional symptoms such as

(1) Significant weight loss or gain

(2) Insomnia or hypersomnia
(3) Psychomotor agitation or retardation
(4) Fatigue or loss of energy
(5) Feelings of worthlessness
(6) Diminished ability to think or concentrate; indecisiveness
(7) Recurrent thoughts of death, suicidal ideation, suicide attempt, or specific plan for suicide
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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.

We must remember next information:

1. Patients with MDD may not initially present with a complaint of low mood,
anhedonia, or other typical symptoms.
2. 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.
3. Elderly persons may present with confusion or a general decline in functioning.
4. Children with MDD also may present with initially misleading symptoms such as
irritability, decline in school performance, or social withdrawal.
5. The differential diagnosis in patients presenting with alterations in mood is extensive
and should include consideration of the following:

• Mood disorders
• Alzheimer disease
• Neoplastic lesions of the CNS
• Inflammatory conditions
• Sleep disorders
• Infectious processes
• Pharmacologic agents
• Endocrinologic disorders
• Substance use, abuse, or dependence
• And others
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Appearance and affect

(слайд 3) Most patients with MDD 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, MDD 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 MDD. 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 MDD 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.

Patients with MDD 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 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.

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.
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Causes: (слайд 4) The specific cause of MDD is not known. As with most psychiatric disorders,
MDD appears to be multifactorial in its origin.

• Biological contributors
• Genetic susceptibility plays a role in the development of MDD. Individuals with a family
history of affective disorders, panic disorder, and alcohol dependence carry a higher risk for
MDD.
• Certain neurologic illnesses increase the risk of MDD. 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 MDD.
• Chronic pain, medical illness, and psychosocial stress also can play a role in both the
initiation and maintenance of MDD.

• Psychosocial contributors: While MDD can arise without any precipitating stressors, stress
and interpersonal losses certainly increase risk. Psychodynamic formulations find that significant
losses in early life predispose to MDD over the lifespan of the individual, as does trauma, either
transient or chronic.

Physical: No physical findings are specific to MDD. Diagnosis lies in the history and the mental
status examination.

Lab Studies:

No diagnostic laboratory tests are available for diagnosis of MDD. Based on the clinical history and
physical findings, focused laboratory studies are useful in excluding potential medical illnesses that
may present as MDD. These might include the following: CBC count, Thyroid-stimulating hormone,
Antinuclear antibody, Electrolytes and calcium levels and renal function test, Liver function tests,
Blood alcohol, blood, CT scan or MRI of the brain and urine toxicology screen and other.

TREATMENT

Medical Care: A wide range of effective treatments is available for MDD. Brief psychotherapy
(eg, cognitive behavioral therapy, interpersonal therapy) has been shown in clinical trials to be
an effective treatment option, either alone or in combination with medication. Medication alone
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also can relieve symptoms. However, the combined approach generally provides the patient with
the quickest and most sustained response.

Initial pharmacotherapy: All antidepressants on the market are potentially effective. Usually, 2-6
weeks at a therapeutic dose level are needed to observe a clinical response. The choice of
medication should be guided by anticipated safety and tolerability, which aid in compliance;
physician familiarity, which aids in patient education and anticipation of adverse effects; and history
of prior treatments. Treatment failures often are caused not by clinical resistance, but by medication
noncompliance, inadequate duration of therapy, or inadequate dosing.

MAOIs include phenelzine (Nardil) and tranylcypromine (Parnate). MAOIs are widely effective in a
broad range of affective and anxiety disorders. Because of the risk of hypertensive crisis, patients
on these medications must follow a low-tyramine diet. Other adverse effects can include insomnia,
anxiety, orthostasis, weight gain, and sexual dysfunction.

Tricyclic antidepressants (TCAs) include amitriptyline (Elavil), nortriptyline (Pamelor), desipramine

(Norpramin), clomipramine (Anafranil), doxepin (Sinequan), protriptyline (Vivactil), trimipramine
(Surmontil), and imipramine (Tofranil). This group has a long record of effitionsy in the treatment of
depression and has the advantage of lower cost. They are used less commonly now because of the
need to titrate the dose to a therapeutic level and because of their considerable toxicity in overdose.

Adverse effects largely are due to their anticholinergic and antihistaminic properties and include
sedation, confusion, dry mouth, orthostasis, constipation, urinary retention, sexual dysfunction, and
weight gain. Caution should be used in patients with cardiac conduction abnormalities.

Atypical antidepressants include bupropion (Wellbutrin), nefazodone (Serzone), mirtazapine

(Remeron), and trazodone (Desyrel). This group also shows low toxicity in overdose and may have
an advantage over the SSRIs by causing less sexual dysfunction. Adverse effects such as
drowsiness and weight gain may tend to improve over time and with higher doses. Trazodone is
very sedating and usually is used as a sleep aid rather than as an antidepressant.

Selective serotonin reuptake inhibitors (SSRI) include fluoxetine (Prozac), paroxetine (Paxil),
sertraline (Zoloft), fluvoxamine (Luvox). This group has the advantage of ease of dosing and low
toxicity in overdose. Common adverse effects include GI upset, sexual dysfunction, and changes in
energy level (ie, fatigue, restlessness).

Nonpharmacologic treatments
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(слайд 6)

Electroconvulsive therapy (ECT) is a highly effective treatment for depression and may have a more
rapid onset of action than drug treatments. Advances in brief anesthesia and neuromuscular
paralysis have improved the safety and tolerability of this modality. Risks include those associated
with brief anesthesia, postictal confusion, and, more rarely, short-term memory difficulties. ECT is
used when a rapid antidepressant response is needed, when drug therapies have failed, when
there is a history of good response to ECT, or when there is patient preference. ECT is particularly
effective in the treatment of delusional depression.

Light therapy: Broad-spectrum light exposure has long been in use for the treatment of SAD. Some
evidence now exists that it may have some efficacy in nonseasonal depression or as an
augmenting agent with antidepressant medication.

Transcranial magnetic stimulation: This modality is in investigational stages for the treatment of
MDD. Initial results suggest that it may be an effective intervention without the risks and adverse
effects of ECT.

Vagus nerve stimulation also is in investigational stages and has shown some efficacy in treatment-
resistant depression.

Diet: Dietary restrictions are necessary only when prescribing MAOIs. Foods high in tyramine,
which can produce a hypertensive crisis in the presence of MAOIs, should be avoided. These foods
include soy sauce, sauerkraut, aged chicken or beef liver, aged cheese, fava beans, air-dried
sausage and similar meats, pickled or cured meat or fish, overripe fruit, canned figs, raisins,
avocados, yogurt, sour cream, meat tenderizer, yeast extracts, caviar, and shrimp paste. Beer and
wine also should be avoided.

Activity: Physical activity and exercise contribute to recovery from MDD. Patients should be
counseled regarding stress reduction.

MEDICATION
The following are examples from various classes of antidepressants and augmenting agents that
are used with TCAs or SSRIs to augment therapeutic effect in resistant depression.

Further Inpatient Care: (слайд 7)

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Inpatient care is indicated in MDD when there is a risk of harm to the patient, to others, or when the
patient's symptoms are sufficiently severe to warrant initiation of treatment in a more controlled
setting. These commonly include situations of depression with psychotic features, progressive
inanition, suicidality, or inability to care for oneself at home. When ECT is indicated as therapy,
many practitioners initiate treatment on an inpatient basis, although outpatient initiation of therapy is
increasingly common.

The current climate of insurance controls on treatment typically does not allow prolonged inpatient
stays in the treatment of MDD. Hospitalization is used more commonly to control acute severe
symptoms, with early discharge to home or to lower levels of care such as partial hospitalization.

Further Outpatient Care: (слайд 8)

The successful treatment of MDD requires good follow-up care after the acute episode is resolved.
This ongoing care usually takes place in an outpatient setting.

MDD tends to be a recurrent condition. While some patients experience a single episode, observing
recurrences over time is more common (50-80%). A percentage of individuals have relapses of
sufficient frequency to warrant long-term use of antidepressants as a preventive therapy. Other
patients can discontinue treatment after resolution of an episode and can restart treatment when
symptoms reappear. Most studies suggest that, once an episode is resolved successfully, treatment
should be continued for 6 months to 1 year to reduce the risk of relapse of symptoms. The decision
to continue treatment beyond that time depends on patient preference and past history of
recurrences.

Psychotherapy is an invaluable treatment modality in the management of MDD, addressing as it

does both potential precipitating and maintaining factors of the depressive episode. In moderate-to-
severe depression, psychotherapy is most effective once the somatic and melancholic symptoms
have improved with medication. While psychotherapy can help with the interpersonal and cognitive
dysfunction that can arise from, and predispose to, depressive illness, long-term psychotherapy
does not appear to have a major role in treating MDD.

Complications:

• Potential complications of MDD may develop across the biopsychosocial spectrum.

• Medical: Completed suicides number more than 30,000 per year in the United States.
Other adverse outcomes may arise from attempts at self-injury, untreated medical conditions, or
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physical decline due to inanition. Medical and surgical prognosis and recovery also are affected
adversely by concurrent MDD.

• Psychosocial: MDD, particularly when chronic or untreated, can contribute to

unemployment or failure in school, social isolation, substance abuse, and marital/family
dysfunction.

Prognosis:

• With appropriate treatment, 70-80% of individuals with MDD can achieve a significant
reduction in symptoms, although as many as 50% of patients may not respond to the initial
treatment trial.

• Untreated at 1 year, 40% of individuals with MDD will continue to meet criteria for the
diagnosis, while an additional 20% will have a partial remission. Partial remission and/or a
history of chronic MDD are risk factors for recurrent episodes and treatment resistance.

Patient Education:

• Education plays an important role in the successful treatment of MDD. Patients should be
aware of the rationale behind the choice of treatment, potential adverse effects, and expected
results. The involvement of the patient in the treatment plan can enhance medication
compliance and referral to counseling. Over the long term, patients also may become aware of
signs of relapse and may seek treatment early.

MISCELLANEOUS

• The most common medical pitfall in the treatment of MDD is the management of treatment
resistance. A certain percentage of patients fail to improve adequately with first-line therapy. At
this point, it becomes important to reassess the patient, the diagnosis, and the treatment plan,
and to have a number of strategies available to offer patients.
• Assessment should include (1) adequacy of medication dose, duration of treatment, and
compliance; (2) accuracy of diagnosis and possible medical conditions; and (3) possible
comorbid psychiatric conditions such as substance abuse, anxiety disorders, or personality
disorders.
• Assuming that (1) the assessment of the diagnosis is correct, (2) there are no significant
complicating diagnoses, and (3) the current treatment has been at a therapeutic dose for a
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sufficient amount of time, possible interventions for persistent symptoms can include the
following:

◊ Increasing the medication dose to the maximum tolerated

◊ Changing to a different antidepressant
◊ Adding psychotherapy or more intensive care if not already completed
◊ Augmenting the current medication
◊ Considering the use of ECT

• Another common pitfall in the treatment of MDD involves the risk of suicidal or homicidal
behavior. Routinely interviewing patients at each visit for suicidal or homicidal ideation and
documenting the assessment are important. Legitimate concern regarding the patient's safety, or
his or her possible danger to others, takes precedence over confidentiality. In such
circumstances, the physician has a duty to act either to prevent self-injury or suicide or to warn
an identified potential target of violence.

Special Concerns:

1. Depression in the postpartum period

• Pregnancy can present a potentially difficult clinical situation when complicated by

depression. MDD is quite common in women during the childbearing years. MDD can have a
significant negative impact on a woman's experience of pregnancy and parenting, as well as on
her functioning as a new parent. As with all medical conditions that arise during pregnancy, the
risks and benefits of pharmacotherapy should be evaluated.
• While it is preferable to avoid the use of medication during pregnancy, the benefits of
prompt medical treatment of MDD often may outweigh the risks of exposure of the fetus to an
antidepressant. While untested in controlled trials, there is no clear evidence that available
antidepressants are teratogenic. In severe depression during pregnancy, especially in cases of
psychosis, agitation, or severe retardation, ECT can be the safest and quickest treatment option.
• Depression in the postpartum period is a common and, potentially, very serious problem.
Prompt diagnosis and intervention are essential to mitigate the negative impact on the mother
and her infant.
• More than 80% of women can develop mood disturbances in the postpartum period. Most
of these women experience a transient syndrome called baby blues, which is characterized by
tearfulness and mood changes that resolve spontaneously in a few days to 2 weeks. However,
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more than 10% of women meet criteria for MDD during the first year following delivery. Many of
these patients are not identified as depressed and do not receive treatment.
• Postpartum psychosis, while far less common, does occur, and is more likely to arise in
patients with a history of psychosis or bipolar disorder.
• Principles of treatment for postpartum MDD are the same as for depression during any
other time of life. The patient should be assessed for danger to herself or to her children, as well
as for other symptoms such as psychosis or substance abuse. Most antidepressants probably
can be used safely during breastfeeding; however, this has not been studied thoroughly, and the
same risk-benefit considerations should be applied as when treating depression during
pregnancy.

2. Seasonal affective disorder

o This is a form of MDD that arises during the winter months and resolves during the spring
and summer months. Studies suggest that SAD also is mediated by alterations in CNS 5-HT.
SAD appears to be triggered by alterations in circadian rhythm and sunlight exposure. Patients
with SAD are more likely to report atypical symptoms such as hypersomnia and increased
appetite.