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

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

  2. Identify the signs and symptoms of MDD.

  3. Outline the treatment goals for a patient with MDD.

  4. Recommend pharmacotherapy given a specific patient with MDD.

  5. Develop a monitoring plan for a specific patient with MDD which includes the assessment of efficacy as well as toxicity.

  6. Predict, prevent, identify, and resolve potential drug-related problems.

  7. Educate patients and caregivers on the proper use of antidepressant therapy.


Major depression is a common, seriously disabling, disorder nonresponsive to volitional efforts to feel better. Individuals with major depressive disorder (MDD) experience pervasive symptoms affecting mood, thinking, physical health, work, and relationships. Suicide often results when MDD is inadequately diagnosed and treated.1

Over and under detection of MDD is an important consideration. Primary care providers have become increasingly involved in the management of MDD. Studies show that over detection of MDD can outnumber missed cases.1 Antidepressants account for 15 of the top 200 prescriptions drugs dispensed in the United States.2 Inadequate treatment remains a serious concern.3

Patient Encounter, Part 1

A 62-year-old man with diabetes, hypertension, and recently diagnosed Parkinson disease presents to the psychiatry clinic. He complains of depressed mood, poor sleep, and appetite. He has lost 25 pounds (11.4 kg) in the last 2 months. He also has been isolating himself from other people, and has had crying spells. He says that he has been thinking about committing suicide, but he does not have a specific plan.

What symptoms of MDD does he have?

What medical or psychiatric issues could be contributing to his symptoms?

What additional information do you need to know before creating a treatment plan for this patient?


The lifetime and 12-month prevalence estimates for MDD are 16.2% and 6.6%, respectively.4 Women are twice as likely as men to experience MDD. The average age of onset is in the mid-twenties; many patients with MDD have comorbid psychiatric disorders, especially anxiety and substance abuse disorders.5

According to the World Health Organization (WHO), depression is the leading cause of disability (based on years lived with disability) and the fourth leading cause of the global burden of disease.6

Symptoms of depression are due to a change in the brain neurotransmitters, norepinephrine (NE), serotonin (5-HT), and dopamine (DA).


The cause of MDD is unknown but is probably multifactorial. Multiple theories abound, and practitioners suggest that development of depression likely involves a complex interaction of genetic predisposition, psychological stressors, and underlying pathophysiology. There are no currently accepted unifying theories to adequately explain the ...

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