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Content Update

June 1, 2019

Newly Approved Medications for treatment-resistant depression in conjunction with an oral antidepressant: The U.S. Food and Drug Administration (FDA) approved intranasal esketamine (Spravato®) for adults who have demonstrated resistance (failed at least two previous trials of adequate dose and duration) to other therapies for major depressive disorder. Intranasal esketamine plus a newly initiated oral antidepressant demonstrated superiority over intranasal placebo and oral antidepressant in reducing symptoms of depression as measured by the Montgomery-Asberg Depression Rating Scale (MADRS).



Upon completion of the 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 adverse effects.

  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 prescription drugs dispensed in the United States.2 Inadequate treatment remains a serious concern.3


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.5 In the United States, incidence peaks in the twenties. Many patients with MDD have comorbid psychiatric disorders, especially anxiety and substance use disorders.5

Patient Encounter Part 1

A 43-year-old woman presents to the psychiatry clinic with complaints of depressed mood, poor sleep, and decreased appetite. She has lost 25 pounds (11.4 kg) in the last 2 months. She also has been isolating herself from other people, and has had crying spells. She says that she has been thinking about committing suicide, but she does not have a specific plan.

What symptoms of MDD does she have?

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

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

According to the World Health Organization (WHO), depression is the leading cause of disability ...

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