A 36-year-old man presents to the office for follow up after initiating antidepressant therapy. Two months ago, he was started on citalopram after several weeks of depressed mood, loss of interest in activities, depressed appetite, and inability to sleep. Today, he reports minimal improvement in his symptoms. He had some nausea after starting the medication, but this has resolved. He denies thoughts of suicide or self-harm. His temperature is 98.6°F (37.0°C), pulse is 80/min, blood pressure is 120/80 mmHg, respirations are 22/min, and oxygen saturation is 97% on room air. Exam reveals a depressed, tired appearing man. Which of the following is the most appropriate next step in management?
Switch to paroxetine
Switch to phenelzine
Electroconvulsive therapy
Add mirtazapine
Add mirtazapine
This patient is being treated for depression without improvement in his symptoms after 6 weeks of medication use. In the setting of his reduced appetite and trouble sleeping, mirtazapine is an appropriate medication to add.

SSRIs (including paroxetine, citalopram, fluvoxamine, sertraline, and fluoxetine) are the first line treatment for major depression. For patients in whom an adequate trial of SSRI therapy has been ineffective, the first step in management is a trial of augmentation with a separate agent prior to switching to a different primary antidepressant medication. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, acts by inhibiting pre-synaptic alpha-2 receptors as well as 5HT2 and 5HT3 serotonin receptors. Notably, its side effect profile includes increased appetite and mild sleepiness, making it a good option for depressed patients with insomnia or decreased appetite. Mirtazapine is commonly used to augment primary antidepressant therapy. Augmentation with an additional agent should generally be attempted prior to switching to a different SSRI or other first line medication.

Davies et. al review the pharmacologic management of depression. They note that while evidence is limited, there is some data to suggest benefit in augmentation with a secondary agent prior to switching to another first line therapy.

Incorrect Answers:
Answer B: Electroconvulsive therapy, while often extremely effective, is typically reserved for patients that are actively suicidal, unable to eat, or displaying psychotic symptoms. It is more commonly used after medications have failed.

Answer C: Switching to amitriptyline, a tricyclic antidepressant, would not be appropriate. Tricyclic antidepressants have a negative side effect profile and potential for severe toxicity.

Answer D: Switching to paroxetine, another SSRI medication, may be appropriate. However, this patient's particular constellation of symptoms (decreased appetite and insomnia) suggest that he would likely respond well to mirtazapine.

Answer E: Switching to phenelzine, a monoamine oxidase inhibitor, would not be appropriate. Monoamine oxidase inhibitors have a negative side effect profile and potential for severe drug-drug interaction.

Bullet Summary:
Mirtazapine (a noradrenergic and serotonergic antidepressant) is an appropriate next step for depressed patients with significant insomnia and decreased appetite who fail to respond to a trial of SSRI monotherapy.