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Upon completion of the chapter, the reader will be able to:

  1. Explain the etiology and pathophysiology of major depressive disorder (MDD).

  2. Identify symptoms and clinical features of MDD.

  3. Differentiate antidepressants according to pharmacologic properties, adverse effect profiles, pharmacokinetic profiles, drug interaction profiles, and dosing features.

  4. Predict adverse effect profiles of antidepressants based on pharmacology.

  5. State the goals of pharmacotherapy in MDD.

  6. Educate patients and caregivers on the proper use of antidepressants.




  • Image not available. Classic views as to the cause of major depressive disorder (MDD) focus on the monoamine neurotransmitters norepinephrine (NE); serotonin (5-HT); and to a lesser extent, dopamine (DA) in terms of both synaptic concentrations and receptor functioning.

  • Image not available. It is not uncommon for a patient to experience only a single major depressive episode, but most patients with MDD experience multiple episodes.

  • Image not available. One extremely important goal in the treatment of MDD is the prevention of suicide attempts.

  • Image not available. Sexual dysfunction, common and challenging to manage, often leads to noncompliance with serotonergic medications.

  • Image not available. Each antidepressant has a response rate of approximately 60% to 80%, and no antidepressant medication or class has been reliably shown to be more efficacious than another.

  • Image not available. It is widely accepted that approximately 2 to 4 weeks of treatment is required before improvement is seen in emotional symptoms of depression, such as sadness and anhedonia. Furthermore, as long as 6 to 8 weeks of treatment may be required to see the full effects of antidepressant therapy.

  • Image not available. Because the typical major depressive episode lasts 6 months or longer, if antidepressant therapy is interrupted for any reason after the acute phase of treatment, the patient may relapse into the depressive episode. When treating the first depressive episode, antidepressants must be given for an additional 4 to 9 months in the continuation phase for the purpose of preventing relapse.

  • Image not available. Pediatric patients and young adults should be observed closely for suicidality, worsened depression, agitation, irritability, and unusual changes in behavior, especially during the initial few months of therapy and at times of dosage changes. Furthermore, families and caregivers should be advised to monitor patients for such symptoms.

  • Image not available. Lack of patient understanding concerning optimal antidepressant drug therapy frequently leads to partial compliance or noncompliance with therapy; thus, the primary purpose of antidepressant counseling is to enhance compliance and improve outcomes.


My spirit is broken, my days are cut short, the grave


awaits me.


—Job 17:1


Contrary to popular belief, major depression is not a fleeting "bad day," is not the result of personal weaknesses or character flaws, and does not respond to volitional efforts simply to feel better. Major depressive disorder (MDD) is a serious medical condition with a biological foundation, and it responds to biological and psychological treatments. Individuals with MDD experience significant and pervasive symptoms that can affect mood, thinking, physical health, work, and relationships. Unfortunately, suicide is often the result ...

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