A 33-year-old man with an unremarkable medical history comes to the office due to fatigue and weight loss over the past 3 months. He awakens at 4:00 AM each day and is unable to fall back asleep. The patient also mentions that he had enjoyed golf and playing with his children but now has little interest in either activity. Although he used to excel at work, he now has no motivation and "spaces out" at times. Physical examination and laboratory studies, including TSH level, are normal. The patient is diagnosed with major depressive disorder and prescribed fluoxetine. Two weeks later, he calls to report that he is sleeping and eating better but is still depressed. The patient is discouraged about his lack of improvement and says, "I don't feel like the medication is doing very much." Which of the following is the most appropriate next step in pharmacological management?

Question

A 33-year-old man with an unremarkable medical history comes to the office due to fatigue and weight loss over the past 3 months.  He awakens at 4:00 AM each day and is unable to fall back asleep.  The patient also mentions that he had enjoyed golf and playing with his children but now has little interest in either activity.  Although he used to excel at work, he now has no motivation and "spaces out" at times.  Physical examination and laboratory studies, including TSH level, are normal.  The patient is diagnosed with major depressive disorder and prescribed fluoxetine.  Two weeks later, he calls to report that he is sleeping and eating better but is still depressed.  The patient is discouraged about his lack of improvement and says, "I don't feel like the medication is doing very much."  Which of the following is the most appropriate next step in pharmacological management?

Quizplus · Accepted Answer

Antidepressants take time to work, and this patient's lack of global improvement at the 2-week mark is not uncommon. In addition, although he still feels depressed, he shows signs of improvement in some depressive symptoms (ie, sleep and appetite) at his current dosage. An adequate antidepressant trial is generally considered to be at least 4-6 weeks. The patient should be educated that 2 weeks is considered an inadequate trial and be encouraged to continue the medication for at least 2-4 more weeks. Inadequate antidepressant dose or duration is a common reason for perceived lack of response, and physicians must ensure that patients receive an adequate trial before recommending next-step treatments. (Choices A and B) Augmentation strategies such as adding aripiprazole or bupropion are generally considered when a patient has experienced a partial response to an adequate trial of monotherapy. It would be premature to add these medications after only 2 weeks of fluoxetine therapy. (Choices D and E) Switching to a different antidepressant is a reasonable strategy if the patient shows little improvement after a 4- to 6-week trial. Discontinuing fluoxetine would risk losing his partial response. (Choice F) Increasing the dose of fluoxetine is not indicated in this patient who is already showing signs of responding (ie, improved sleep and appetite) and would unnecessarily increase his risk of adverse effects. Educational objective: Adequate duration of an antidepressant trial is generally considered to be 6 weeks. Physicians should continue antidepressants at therapeutic dosages for at least 4-6 weeks before considering the next step in treatment. References: Systematic review of clinical practice guidelines for failed antidepressant treatment response in major depressive disorder, dysthymia, and sub threshold depression in adults. (http://www.ncbi.nlm.nih.gov/pubmed/27554483) Serotonergic drugs for depression and beyond. (http://www.ncbi.nlm.nih.gov/pubmed/23531115) When should you move beyond first-line therapy for depression? (http://www.ncbi.nlm.nih.gov/pubmed/20977871)

A 33-Year-Old Man with an Unremarkable Medical History Comes to the Office