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Annals for Educators - 1 March 2016Annals for Educators - 1 March 2016 FREE

Darren B. Taichman, MD, PhD
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From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Associate Dean of Graduate Medical Education and Affiliations, Thomas Jefferson University.

Ann Intern Med. 2016;164(5):ED5. doi:10.7326/AFED201603010
© 2016 American College of Physicians
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This American College of Physicians guideline provides clinical recommendations for treating major depressive disorder in adults with second-generation antidepressants or nonpharmacologic treatments, such as psychotherapy, complementary and alternative medicine, and exercise. ACP recommends that clinicians select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient.

Use this guideline to:

  • Start a teaching session with multiple-choice question 1 below.

  • Ask your learners to list the ways in which depression might present. How is a diagnosis established? Should we screen for depression?

  • How would your learners explain the advantages and disadvantages of pharmacologic and cognitive behavioral therapies to their patients? What factors would they discuss to help decide which is best for each patient?

  • What are the potential side effects of second-generation antidepressants?

  • What does cognitive behavioral therapy involve, and how is it arranged for a patient? Invite a therapist to join your discussion, or if possible, arrange for your learners to observe a therapy session.

  • Now, pose multiple-choice question 2 below to your learners. Ask how your learners monitor their patients' response to depression therapy. When should a change in treatment be considered?

Tobacco use remains the principal cause of preventable death in the United States, accounting for an estimated 480,000 deaths and over $289 billion in health costs annually. The CDC estimates that 17.8% of adults and 9.2% of high school students smoke cigarettes. This review discusses how to help patients quit, what problems are to be anticipated, and what may be done to maximize success.

Use this review to:

  • Ask your learners to list the health benefits of smoking cessation, and over what time frame they are likely to occur. Use the information contained in the Box to answer.

  • What are the 5 A's? Do your learners know how to do each?

  • What pharmacologic and nonpharmacologic aids should be considered to assist in smoking cessation? What are the side effects of the drugs used? How effective are they? Use the information in the Table.

  • What adverse effects might a patient encounter upon quitting (e.g., weight gain, depression)?

  • Ask your learners what approach should be taken to smoking cessation in a pregnant woman.

  • What are the arguments in favor of or against electronic cigarettes as alternatives to combustible cigarettes? Use the concise discussions in a recent pro/con debate (Bartter and Drummond).

  • Use the already provided multiple-choice questions to introduce topics throughout a teaching session. Log on and enter your answers to earn CME for yourself! Download the teaching slides to help you prepare a teaching session.

This short, silent video reveals a patient's hidden worries, and misconceptions, that impede his initiation of recommended therapy.

Use this feature to:

  • Watch the short video, and ask your learners if they have discovered other “hidden” misconceptions regarding a disease or its therapy that impeded a patient's adherence to appropriate therapy.

  • What might this short video teach us about how to approach a patient's nonadherence? What questions should we be asking?

  • Teach at the bedside! Ask a patient who uses insulin if s/he would mind discussing with your team the worries s/he had prior to its initiation. How did things work out?

  • Consider combining the use of this video with a recent, related Annals Graphic Medicine: The Daily Grind: A Day in the Life of Someone Living With Diabetes about the same patient earlier in the course of his diabetes. Start with this video, and discuss the burdens of living with a chronic disease. Ask your learners whether they think they could keep up with the regimens we commonly prescribe. And, here too, discuss how important issues that impede adherence might remain hidden if we don't probe.

(Mobile users can access the video here.)

Story Slams bring people together to listen and share. In the tradition of the popular Annals feature, physicians share poignant and inspiring moments at this Annals On Being a Doctor Story Slam.

Use this feature to:

  • Watch this short video in which Dr. Travis Baggett describes the unexpected outcome of his interaction with a homeless man at a shelter.

  • Ask your learners whether they ever feel helpless themselves when confronting a patient for whom the prospect of “improvement” seems hopeless. Is there truly ever a situation in which there is no way to help a patient start along a better path?

  • Have your learners ever found themselves doing something unexpected with or for a patient? What? How did it turn out?

  • Why do your learners think Dr. Travis' actions might have affected his patient so?

A 68-year-old woman is evaluated for memory deficits. She retired from her position as a high school principal 2 years ago. In the past 6 months, she has had increasing forgetfulness, difficulty organizing her belongings, and problems with concentration and indecisiveness; during this period, she also has noticed fatigue, decreased energy, difficulty falling asleep, diminished interest in reading, and decreased appetite, which has caused her to lose 4.5 kg (10.0 lb). The patient has remained independent in activities of daily living, although she has forgotten to pay several monthly bills. She moved closer to her son last year but now has few opportunities to see her friends, which has resulted in feelings of isolation and sadness. The patient had a depressive episode 28 years ago after her husband's death. She takes no medication.

On physical examination, vital signs and general physical examination findings are normal. Neurologic examination reveals psychomotor slowing without decremental response on repetitive finger tapping. The patient scores 27/30 on the Mini–Mental State Examination, losing three points in the attention and calculation section.

Results of a complete blood count, a comprehensive metabolic profile, thyroid function tests, and urinalysis are normal.

Which of the following is the most appropriate next step in management?

A. Carbidopa-levodopa

B. Donepezil

C. Sertraline

D. Clinical observation

Correct Answer

C. Sertraline

Educational Objective

Treat depression-related cognitive impairment.


The patient's symptoms are consistent with a major depressive episode, which should be treated with sertraline. More than half of patients with late-life major depression exhibit clinically significant cognitive impairment, most frequently affecting processing speed, executive function, and visuospatial ability. Her feelings of isolation and sadness, previous depressive episode, loss of interest in reading, loss of energy, poor concentration, indecisiveness, and significant weight loss are all suggestive of major depression. Depression-related cognitive impairment, historically known as pseudodementia, can be difficult to distinguish from early degenerative diseases. Cognitive testing may show objective impairment of working memory, attention, executive function, and processing speed. Psychomotor slowing, also known as psychomotor retardation, refers to reduced processing speed and motor activity, such as in speech and fine- and gross-motor skills. Psychomotor slowing is a common feature of severe depression. First-line treatment of major depression includes pharmacotherapy, with or without psychotherapy. Each patient should be clinically treated and then monitored for effectiveness of therapy, continued need for pharmacotherapy, and response of cognitive symptoms.

Carbidopa-levodopa is an effective medication for symptomatic treatment of Parkinson disease (PD). This patient exhibits psychomotor slowing but lacks the decremental response (decreased speed and amplitude) on repetitive movements typical of PD and also other defining features of PD. This medication is not effective in treating major depression.

Donepezil is a cholinesterase inhibitor that can be effective in improving cognitive symptoms and function in patients with Alzheimer disease. This patient's history and results of cognitive testing are not consistent with a diagnosis of dementia. Although depression can represent a prodrome to PD, Alzheimer disease, and other neurodegenerative conditions and often accompanies these conditions, cholinesterase inhibitors are not effective in treating major depression.

Depression is often unrecognized and undertreated in the elderly and is not a consequence of normal aging. Late-life depression has been associated with an increased risk of dementia and should be treated aggressively. Therefore, clinical observation is insufficient as management.

Key Point

First-line treatment of major depression in patients with cognitive impairment is pharmacotherapy, with or without psychotherapy.


Pellegrino LD, Peters ME, Lyketsos CG, Marano CM. Depression in cognitive impairment. Curr Psychiatry Rep. 2013 Sep;15(9):384.

A 38-year-old man is evaluated during a follow-up visit. Eight weeks ago, he was diagnosed with a first episode of depression based on symptoms of depressed mood, fatigue, increased sleep, anhedonia, and weight gain. His score on the PHQ-9 was 15 (moderately severe depression). Citalopram, 20 mg/d, was initiated at that time. Six weeks ago, he was tolerating the medication with no significant side effects but without improvement of symptoms; citalopram was therefore increased to the maximum dose of 40 mg/d. Currently, he reports no improvement of his depressive symptoms, and his PHQ-9 score remains 15. He has no suicidal ideation.

On physical examination, the patient has a mildly depressed affect but responds appropriately. Vital signs are normal, and the remainder of the examination is unremarkable.

Which of the following is the most appropriate next step in management?

A. Add liothyronine

B. Discontinue citalopram and begin bupropion

C. Discontinue citalopram and begin olanzapine

D. Refer for electroconvulsive therapy

Correct Answer

B. Discontinue citalopram and begin bupropion

Educational Objective

Manage depression that does not respond to full-dose antidepressant monotherapy.


Discontinuation of citalopram and initiation of a different antidepressant such as bupropion is the most appropriate next step in the management of this patient. About 40% of patients with depression do not respond to antidepressant monotherapy. However, patients who do not respond to full-dose antidepressant monotherapy for 6 weeks may respond to switching to a different antidepressant drug, either from the same or a different class, or the addition of a second antidepressant drug.

Available evidence is not convincing regarding the efficacy of liothyronine in combination with, or augmenting, selective serotonin reuptake inhibitor treatment of depression.

Patients who do not respond to full-dose antidepressant monotherapy for 6 weeks may respond to the addition of an antipsychotic drug. The FDA has approved the following combinations of antidepressant and antipsychotic drugs for the treatment of depression: aripiprazole or quetiapine extended-release added to any antidepressant, and olanzapine added to fluoxetine. However, olanzapine monotherapy is not an appropriate treatment for this patient.

Electroconvulsive therapy may be appropriate for patients with depression refractory to multiple antidepressant drugs (or intolerance of such drugs), with or without psychotherapy, and patients with severe life-threatening depression (for example, suicidal ideation and catatonia).

Most patients with depression are treated with either antidepressant drugs or psychotherapy; a minority receive combined therapy. However, in a recent meta-analysis, pharmacotherapy combined with psychotherapy was more effective than pharmacotherapy alone in the treatment of depression. In addition to switching to a different antidepressant or adding a second antidepressant or an antipsychotic agent, clinicians should consider psychotherapy for depressed patients who do not respond to antidepressant drug monotherapy.

Key Point

Patients refractory to full-dose antidepressant monotherapy within 6 weeks may respond to a change in therapy, which may include replacement with another antidepressant, either from the same or a different class, or the addition of a second antidepressant.


Gaynes BN, Dusetzina SB, Ellis AR, et al. Treating depression after initial treatment failure: directly comparing switch and augmenting strategies in STAR*D. J Clin Psychopharmacol. 2012 Feb;32(1):114-9.

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