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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. 8th ed. Accessed June 19, 2012

  • Unipolar depression
  • Major depression

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

  • Several social, developmental, and biologic theories proposed.
  • Patient symptoms reflect changes in brain monoamine neurotransmitters, specifically norepinephrine (NE), serotonin (5-HT), and dopamine (DA).

  • 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.

  • 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.

Signs and Symptoms

  • Emotional symptoms:
    • Diminished ability to experience pleasure
    • Loss of interest in usual activities
    • Sadness
    • Pessimistic outlook
    • Crying spells
    • Hopelessness
    • Anxiety
    • Feelings of guilt
    • Psychotic features (e.g., auditory hallucinations and delusions)
  • Physical symptoms:
    • 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.

Means of Confirmation and Diagnosis

Laboratory Tests

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

Differential Diagnosis

  • Bipolar disorder or cyclothymia
  • Adjustment disorder with depressed mood
  • Dysthymia
  • Premenstrual dysphoric disorder
  • Major depression with postpartum onset: usually 2 weeks to 6 months postpartum
  • Seasonal affective disorder
  • Substance use disorders
  • Medications (e.g., clonidine, propranolol, reserpine, isotretinoin)

  • Eliminate or reduce acute symptoms.
  • Minimize adverse drug effects.
  • Ensure adherence with therapeutic regimen.
  • Facilitate return to premorbid level of functioning.
  • Prevent further depressive episodes.

  • Antidepressants essentially equal in efficacy when administered in comparable doses.
  • Choice of antidepressant based on:
    • Patient’s history of response
    • History of familial response
    • Concurrent medical conditions
    • Presenting symptoms
    • Potential ...

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