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  • The essential feature of major depressive disorder (MDD) is a clinical course characterized by one or more major depressive episodes without a history of manic or hypomanic episodes.

  • The reader is referred to the Practice Guideline for the Treatment of Patients with Major Depressive Disorder developed by the American Psychiatric Association and the guideline of the British Association of Psychopharmacology.


  • Biogenic amine hypothesis: Decreased brain levels of the neurotransmitters norepinephrine, serotonin (5-HT), and dopamine may cause depression.

  • Postsynaptic changes in receptor sensitivity: Studies have demonstrated that desensitization or downregulation of norepinephrine or 5-HT1A receptors may relate to onset of antidepressant effects.

  • Dysregulation hypothesis: This theory emphasizes a failure of homeostatic regulation of neurotransmitter systems, rather than absolute increases or decreases in their activities.

  • 5-HT/norepinephrine link hypothesis: This theory suggests that 5-HT and norepinephrine activities are linked, and that both the serotonergic and noradrenergic systems are involved in antidepressant response.

  • The role of dopamine: Evidence suggests that dopamine transmission is decreased in depression and that increased dopamine activity in the mesolimbic pathway contributes to antidepressant activity.

  • Disruption of brain derived neurotrophic factor expression in the hippocampus may be associated with depression.


  • Emotional symptoms: diminished ability to experience pleasure, loss of interest in usual activities, sadness, pessimism, crying, hopelessness, anxiety, guilt, and psychotic features (eg, auditory hallucinations and delusions).

  • Physical symptoms: fatigue, pain (especially headache), sleep disturbance, decreased or increased appetite, loss of sexual interest, and gastrointestinal (GI) and cardiovascular complaints (especially palpitations).

  • Intellectual or cognitive symptoms: decreased ability to concentrate, poor memory for recent events, confusion, and indecisiveness.

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


  • Major depressive disorder is characterized by one or more major depressive episodes, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Five or more of the following must have been present nearly every day during the same 2-week period and cause significant distress or impairment (NOTE: depressed mood or loss of interest or pleasure must be present in adults [or irritable mood in children and adolescents]): depressed mood; diminished interest or pleasure in almost all activities; weight loss or gain; insomnia or hypersomnia; psychomotor agitation or retardation; fatigue or loss of energy; feelings of worthlessness or excessive guilt; diminished concentration or indecisiveness; recurrent thoughts of death, suicidal ideation without a specific plan, suicide attempt, or a plan for committing suicide. The depressive episode must not be attributable to physiological effects of a substance or medical condition. Lastly, there must not be a history of manic-like or hypomanic-like episodes unless they were induced by a substance or medical condition.

  • Diagnosis requires a medication review, physical examination, mental status examination, a complete blood count with differential, thyroid function tests, and electrolyte determination.

  • Many chronic ...

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