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SOURCE

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Source: Teter CJ, Kando JC, Wells BG. Major depressive disorder. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146064868.

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CONDITION/DISORDER SYNONYMS

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  • Unipolar depression.

  • Major depression.

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DEFINITION

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  • Affective disorder characterized by one or more major depressive episodes without history of manic, mixed, or hypomanic episodes.

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ETIOLOGY

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  • Several social, developmental, and biologic theories proposed.

  • Patient symptoms reflect changes in brain monoamine neurotransmitters, specifically norepinephrine (NE), serotonin (5-HT), and dopamine (DA).

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PATHOPHYSIOLOGY

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  • Depression may be caused by decreased brain levels of norepinephrine, 5-HT, and dopamine.

  • Desensitization or downregulation of norepinephrine or 5-HT1A receptors may relate to onset of antidepressant effects.

  • Failure of homeostatic regulation of neurotransmitter systems, rather than absolute increases or decreases in their activities, may be involved.

  • Potential link between 5-HT and norepinephrine activity—both serotonergic and noradrenergic systems involved in antidepressant response.

  • Increased dopamine neurotransmission in mesolimbic pathway may be related to mechanism of action of antidepressants.

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EPIDEMIOLOGY

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  • In one survey, 16.2% of population had history of major depressive disorder in their lifetime, and >6.6% had episode within past 12 months.

  • Women have lifetime rate 1.7–2.7 times greater than for men.

  • Adults 18–29 years of age have highest rates during any given year.

  • Depressive disorders common during adolescence, with comorbid substance abuse, suicide attempts, and deaths occurring frequently.

  • Depressive disorders and suicide tend to occur within families.

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CLINICAL PRESENTATION

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SIGNS AND SYMPTOMS
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  • Emotional symptoms:

    • Diminished ability to experience pleasure.

    • Loss of interest in usual activities, hobbies, or work.

    • Sadness.

    • Pessimistic outlook.

    • Crying spells.

    • Hopelessness.

    • Anxiety.

    • Feelings of guilt.

    • Psychotic features (eg, auditory hallucinations and delusions)

  • Physical symptoms:

    • Chronic fatigue.

    • Headache.

    • Pain.

    • Sleep disturbance.

    • Increased/decreased appetite.

    • Loss of sexual interest.

    • Gastrointestinal (GI) and cardiovascular complaints (especially palpitations)

  • Cognitive symptoms:

    • Decreased ability to concentrate.

    • Slowed thinking.

    • Poor memory for recent events.

    • Confusion.

    • Indecisiveness.

  • Psychomotor disturbances may include psychomotor retardation (slowed physical movements, thought processes, and speech) or psychomotor agitation.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Documenting one or more episodes of major depression, as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th ed.

  • Symptoms present nearly every day for at least 2 weeks.

  • When patient presents with depressive symptoms, investigate possibility of medical, psychiatric, or drug-induced cause.

  • Perform complete medication review, physical examination, mental status examination.

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LABORATORY TESTS
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  • Obtain complete blood count (CBC) with differential, thyroid-stimulating hormone, and serum electrolytes.

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DIFFERENTIAL DIAGNOSIS
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  • Bipolar disorder or cyclothymia.

  • Adjustment disorder with depressed mood.

  • Dysthymia.

  • Premenstrual dysphoric disorder.

  • Major depression with postpartum onset: usually 2 ...

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