A 43-year-old woman comes to the office for a follow-up appointment. She was diagnosed with major depressive disorder a year ago and was prescribed citalopram, which provided no symptom relief. The patient was then switched to sertraline, and the dose was gradually increased. She is now taking the highest recommended dose, which she tolerates without difficulty. Although the patient has experienced 50% improvement in depression, she still has symptoms. Specifically, she continues to have low energy and sleeps 12 hours a day without feeling rested. She also describes an increased appetite with recent weight gain of 4.5 kg (10 lb) and poor libido. The patient says, "I really hoped I would feel back to my normal self, but my lack of energy drags me down. I'm reluctant to discontinue sertraline because I feel it has helped somewhat." The patient is married with 2 children and works as a grade school teacher. She describes her marriage as "good" but is concerned that her husband is becoming frustrated with her. She does not smoke or use alcohol. Blood pressure is 128/76 mm Hg and pulse is 64/min. BMI is 28 kg/m². Physical examination is normal. Which of the following is the most appropriate change in pharmacotherapy?

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Explanation: 11ec2b69_c04f_5de1_8f63_05b2e76019ee_MD0005_00 Treatment-resistant depression is defined as major depressive disorder that does not respond to adequate trials of 2 different antidepressants. Pharmacological treatment for patients with treatment-resistant depression includes augmenting with a second agent or switching to an alternate monotherapy. Patients with little to no improvement (nonresponders) or unacceptable tolerability generally benefit from switching to another antidepressant. On the other hand, for partial responders (such as this patient) who are otherwise tolerating their current antidepressant, augmentation is considered a first-line option. In these patients, 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. This patient has had partial improvement on sertraline, a selective serotonin reuptake inhibitor (SSRI), but has persistent symptoms of hypersomnia, fatigue, and weight gain. Her low libido could be a symptom of her underlying depression or a sexual side effect of sertraline. Bupropion, a norepinephrine dopamine reuptake inhibitor, has been shown to be an effective augmentation strategy. Bupropion is an ideal choice as it is an activating antidepressant that does not cause weight gain or sexual side effects and has been used to treat SSRI-induced sexual side effects. (Choice B) Although mirtazapine does not cause sexual dysfunction, it is associated with increased appetite, weight gain, and sedation, which would be problematic for this patient. (Choice C) Phenelzine, a monoamine oxidase inhibitor, would be contraindicated as an augmenting agent due to the risk of serotonin syndrome when used in combination with an SSRI. Phenelzine can be considered as alternate monotherapy in treatment-resistant patients, but it requires a 2-week washout period (5 weeks for fluoxetine due to its longer half-life) due to the risks of hypertensive crisis or serotonin syndrome. (Choice D) Aripiprazole, a second-generation antipsychotic, is an effective augmentation strategy for major depression. However, it is not used as monotherapy. (Choice E) Paroxetine is an SSRI, as are citalopram and sertraline. There would be little reason to expect that the patient would experience a better response than she had with sertraline. In addition, paroxetine is associated with weight gain, which would be undesirable in this patient. Educational objective: Depressed patients with a partial response to monotherapy may benefit from augmentation with a second agent. Patients who show no response to initial therapy or who have significant side effects should be switched to a different antidepressant. References: Bupropion as an augmenting agent in patients of depression with partial response. (http://www.ncbi.nlm.nih.gov/pubmed/21895979) Managing partial response or nonresponse: switching, augmentation, and combination strategies for major depressive disorder. (http://www.ncbi.nlm.nih.gov/pubmed/19922740) Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant. (http://www.ncbi.nlm.nih.gov/pubmed/27141292)

A 43-Year-Old Woman Comes to the Office for a Follow-Up