A 53-year-old man comes to the office due to persistent fatigue. The patient started a therapeutic dose of fluoxetine 2 months ago after being diagnosed with major depressive disorder. He says, "Since I last saw you, I still feel like I'm dragging pretty much every day and have to force myself to go to work in the mornings. I haven't even wanted to have sex with my wife. That's been going on for almost a month, and it's really bothering me." The patient works as a high school English teacher and notes, "It takes me so long to grade my students' essays because I am so easily distracted." Medical history includes hypertension treated with enalapril. He had a 4-kg (9-lb) weight gain over the past 2 months. Blood pressure is 130/84 mm Hg and pulse is 76/min. Physical examination shows no abnormalities. The patient appears depressed and speaks softly throughout the interview. Which of the following is the most appropriate next step in pharmacotherapy?

Question

A 53-year-old man comes to the office due to persistent fatigue.  The patient started a therapeutic dose of fluoxetine 2 months ago after being diagnosed with major depressive disorder.  He says, "Since I last saw you, I still feel like I'm dragging pretty much every day and have to force myself to go to work in the mornings.  I haven't even wanted to have sex with my wife.  That's been going on for almost a month, and it's really bothering me."  The patient works as a high school English teacher and notes, "It takes me so long to grade my students' essays because I am so easily distracted."  Medical history includes hypertension treated with enalapril.  He had a 4-kg (9-lb) weight gain over the past 2 months.  Blood pressure is 130/84 mm Hg and pulse is 76/min.  Physical examination shows no abnormalities.  The patient appears depressed and speaks softly throughout the interview.  Which of the following is the most appropriate next step in pharmacotherapy?

Quizplus · Accepted Answer

This patient's major depressive disorder has failed to respond to an adequate trial (≥6 weeks) of the selective serotonin reuptake inhibitor (SSRI) fluoxetine. In addition to his persistent depressive symptoms, he is now experiencing decreased libido that may be an SSRI-related adverse effect. Although SSRIs are commonly prescribed as an initial treatment for major depressive disorder, they commonly cause sexual dysfunction (decreased libido, decreased arousal, anorgasmia, increased ejaculation latency). Patients who have no significant response or unacceptable tolerability to an adequate antidepressant trial generally benefit from a switch to a different antidepressant rather than augmentation with a second agent. Antidepressant selection should take the patient's specific depressive symptoms and medication side effect profiles into consideration. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is an antidepressant that does not cause sexual dysfunction. It also has stimulating effects and does not cause weight gain, making it a preferred choice in this patient with persistent fatigue and weight gain. (Choices A and B) Continuing fluoxetine and adding aripiprazole or methylphenidate could be considered in a patient who has had a partial response to fluoxetine without tolerability issues. These interventions would not be appropriate for a patient with a poor response to fluoxetine who may be experiencing sexual dysfunction. (Choice D) The antidepressant venlafaxine is a serotonin-norepinephrine reuptake inhibitor. Like fluoxetine, it is associated with sexual side effects, making switching to bupropion a better option for this patient. (Choice E) This patient had an adequate trial of fluoxetine without improvement and had probable sexual side effects. Increasing the dose is unlikely to improve his depression and may worsen sexual functioning. (Choice F) Adding the phosphodiesterase-5 inhibitor sildenafil is an option for SSRI responders who are experiencing sexual adverse effects. However, it would not be appropriate in this patient who has not responded to fluoxetine. Educational objective: Nonresponders to an adequate trial of a selective serotonin reuptake inhibitor (SSRI) should be switched to another antidepressant. Bupropion, a norepinephrine dopamine reuptake inhibitor that does not cause sexual side effects, is a preferred choice in patients with SSRI-related sexual dysfunction. References: Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. (http://www.ncbi.nlm.nih.gov/pubmed/27141292) Bupropion in the depression-related sexual dysfunction: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/24923342)

A 53-Year-Old Man Comes to the Office Due to Persistent