A 56-year-old woman with major depressive disorder comes to the office for follow-up. Three months ago she was started on fluoxetine 20 mg. Her dosage was subsequently increased to 40 mg after 4 weeks due to nonresponse. At today's visit, the patient says she is "discouraged" and continues to feel sad and unmotivated. Her energy remains low and she sleeps 9-10 hours a day without feeling rested. Although she forces herself to go out with friends, she has difficulty enjoying these occasions. The patient also describes an increased appetite and is discouraged by having gained an additional 2.3 kg (5 lb) since her last visit. She is not interested in psychotherapy at this time. The patient is tolerating fluoxetine without difficulty and takes no other medication. She does not use tobacco or alcohol.
Blood pressure is 128/70 mm Hg and pulse is 68/min. BMI is 25 kg/m². Physical examination is normal. Mental status examination is remarkable for sad affect and no suicidal ideation.
Which of the following is the most appropriate next step in treatment of this patient?

Question

Quizplus · Accepted Answer

Pharmacologic treatment options for patients with treatment-resistant depression include switching to another antidepressant or augmenting with a second agent. This patient has failed to respond to an adequate trial (>6 weeks) of high-dose fluoxetine. Patients with little to no improvement (nonresponders) or unacceptable tolerability generally benefit from switching to another antidepressant rather than augmentation. Discontinuing fluoxetine and starting venlafaxine, a serotonin-norepinephrine reuptake inhibitor, would be the most appropriate next step. Partial responders, in contrast, can consider augmentation as a first-line option as switching carries a risk of losing the partial therapeutic benefit from the original drug. Augmentation strategies include adding a second-generation antipsychotic, an antidepressant with a different mechanism of action, or occasionally lithium or triiodothyronine. (Choice A) This patient has had no improvement on fluoxetine, so adding mirtazapine, an antidepressant that is sedating and increases appetite, would be a poor choice given her symptoms of low energy and weight gain. (Choice B) This patient has already taken fluoxetine 40 mg for 8 weeks with no improvement. Waiting an additional 4 weeks is unlikely to be beneficial and may unnecessarily prolong her suffering. (Choice C) The second-generation antipsychotic aripiprazole is an effective augmentation strategy for treatment-resistant major depression. However, it is not used as monotherapy. (Choice D) Phenelzine, a monoamine oxidase inhibitor, can be considered as alternate monotherapy in treatment-resistant patients. However, due to the risks of hypertensive crisis or serotonin syndrome, it is generally reserved for patients who have failed more than 2 antidepressant trials. In addition, a 5-week washout period would be required due to fluoxetine's long half-life. Educational objective: Patients who are nonresponders to an adequate trial of their initial antidepressant should generally be switched to a different antidepressant. Partial responders may benefit from augmentation with a second agent. __________ References: Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. (http://www.ncbi.nlm.nih.gov/pubmed/19922740) Switching and stopping antidepressants. (http://www.ncbi.nlm.nih.gov/pubmed/27346915)

A 56-Year-Old Woman with Major Depressive Disorder Comes to the Office