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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.

  • Refer to guidelines published by the American Psychiatric Association, the British Association of Psychopharmacology, and the Canadian Network for Mood and Anxiety Treatments (CANMAT) because they have similarities in their recommendations.


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

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

  • Dysregulation hypothesis: Failure of homeostatic neurotransmitter regulation, rather than absolute increases or decreases in their activities.

  • Inflammatory hypothesis: Chronic stress and inflammation may alter glutamatergic and GABA transmission. Brain-derived neurotrophic factor (BDNF) is a primary mediator of neuronal changes as well as synaptogenesis whose expression is reduced due to stress and may be associated with depression.

  • Neuroactive steroids are a growing area of research for depression.


  • Emotional symptoms: Diminished ability to experience pleasure, loss of interest in usual activities, sadness, pessimism, crying, hopelessness, anxiety, feelings of worthlessness or guilt, and psychotic features (eg, auditory hallucinations and delusions). Recurrent thoughts of death, suicidal ideation without a specific plan, suicide attempt, or a plan for committing suicide.

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

  • 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.


  • MDD 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 above symptoms must have been present nearly every day during the same 2-week period and cause significant distress or impairment. Depressed mood or loss of interest or pleasure must be present in adults (or irritable mood in children and adolescents). Table 68-1 outlines a common acronym for MDD diagnostic criteria.

  • The depressive episode must not be attributable to physiological effects of a substance or medical condition.

  • 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 illnesses (eg, stroke, Parkinson disease, traumatic brain injury, hypothyroidism) and substance abuse and dependence disorders are associated with depression. Medications associated with depressive symptoms include many antihypertensives, oral contraceptives, isotretinoin, interferon-β1a, and many others.

  • Standardized rating scale should be used to diagnose depression ...

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