A 48-year-old man comes to the office for a follow-up appointment. He has a history of type 2 diabetes, hypertension, and major depression. Over the past year, the patient has been treated with fluoxetine 20 mg for depression, which was subsequently increased to 40 mg. He says, "I feel about 50% better. I'm definitely less sad, and I'm somewhat more interested in my work and spending time with family. However, I still feel like my energy is low. I used to go to the gym or attend my son's soccer games on weekends, but now all I want to do is rest in bed or on the couch. I'm frustrated because I'm eating too much and haven't been able to lose any weight." Physical examination and routine laboratory tests are unremarkable. Which of the following medications would be most appropriate to augment this patient's antidepressant therapy?

Question

A 48-year-old man comes to the office for a follow-up appointment.  He has a history of type 2 diabetes, hypertension, and major depression.  Over the past year, the patient has been treated with fluoxetine 20 mg for depression, which was subsequently increased to 40 mg.  He says, "I feel about 50% better.  I'm definitely less sad, and I'm somewhat more interested in my work and spending time with family.  However, I still feel like my energy is low.  I used to go to the gym or attend my son's soccer games on weekends, but now all I want to do is rest in bed or on the couch.  I'm frustrated because I'm eating too much and haven't been able to lose any weight."  Physical examination and routine laboratory tests are unremarkable.  Which of the following medications would be most appropriate to augment this patient's antidepressant therapy?

Quizplus · Accepted Answer

The goal of treating major depression is to return patients to their baseline, nondepressed state. However, many patients do not achieve remission and have persistent depressive symptoms and functional impairment. For patients who have had a partial response (generally defined as 25%-50% improvement) to first-line treatment and are tolerating their current medication, major augmentation strategies include adding an antidepressant with a different mechanism of action, a second-generation antipsychotic (eg, aripiprazole), lithium, triiodothyronine, or psychotherapy. This patient with persistent symptoms of low energy and increased appetite had a partial response to first-line treatment with fluoxetine, a selective serotonin reuptake inhibitor (SSRI). Bupropion, a norepinephrine-dopamine reuptake inhibitor, has been shown to be an effective augmentation strategy to SSRI therapy. Bupropion has activating effects and a favorable side-effect profile (no weight gain or sexual side effects), making it a preferred choice for this patient with low energy and weight gain. Unlike partial responders, nonresponders (ie, patients with little to no improvement or unacceptable tolerability to first-line therapy) generally benefit from switching to a different antidepressant. (Choice B) Buspirone is primarily used to treat anxiety disorders. It may be used as augmentation for major depression when augmentation with a second antidepressant is ineffective. (Choice C) Citalopram shares the same mechanism of action as fluoxetine (both are SSRIs). When prescribing a second antidepressant for augmentation, it is preferable to use a drug with a distinct mechanism of action. (Choice D) There is limited evidence to routinely recommend the use of stimulants in adult depression. There is some evidence for their use in elderly patients who have treatment-resistant depression with prominent symptoms of apathy. (Choice E) The antidepressant mirtazapine can be used as augmentation, but its adverse effects of sedation, fatigue, and weight gain would make it a poor choice for this patient. (Choice F) Olanzapine, a second-generation antipsychotic, is an effective augmentation strategy for major depression. However, the risk of weight gain and metabolic adverse effects associated with this drug would make it a less preferred option for a patient with diabetes and hypertension. (Choice G) Adding phenelzine, a monoamine oxidase inhibitor, is contraindicated due to the risk of serotonin syndrome when used in combination with an SSRI. Educational objective: Augmentation with bupropion is an option for treatment of patients with depression with partial response to selective serotonin reuptake inhibitors (SSRIs). Bupropion has activating effects and a favorable side-effect profile (no weight gain or sexual side effects), making it a good choice for patients who are on SSRI therapy but have fatigue, weight gain, or a history of sexual side effects. References: Bupropion as an augmenting agent in patients of depression with partial response. (http://www.ncbi.nlm.nih.gov/pubmed/21895979) Comparing outcomes of adjunctive treatment in depression: aripiprazole versus bupropion. (http://www.ncbi.nlm.nih.gov/pubmed/24767005) Comparison of the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder unresponsive to selective serotonin reuptake inhibitors: a randomized, prospective, open-label study. (http://www.ncbi.nlm.nih.gov/pubmed/28129308)

A 48-Year-Old Man Comes to the Office for a Follow-Up