A 46-year-old man comes to the office with a 2-month history of depressed mood, low energy, and problems concentrating at work. The patient has gained 4.5 kg (10 lb) and is disgusted with himself for not exercising. He sleeps 14 hours a day and has difficulty getting out of bed. He becomes tearful when describing how he loves his children but no longer feels happy to see them. The patient denies any suicidal ideation, intent, or plan, but acknowledges that he contemplated suicide 4 years ago during his divorce proceedings. At that time, he did not seek treatment but felt better over the course of the subsequent year. The patient's physical examination and laboratory studies are within normal limits. He is diagnosed with major depressive disorder and started on escitalopram. After 6 weeks, there is no improvement and the patient is switched to sertraline, which is titrated up to the maximum dose. On a follow-up visit 2 months later, he says that his depressive symptoms are only minimally improved. The decision is made to discontinue sertraline and start a new medication. Which of the following medications would be most appropriate for this patient?
Antidepressant classification & major drugs | |
SSRI |
|
SNRI |
|
NDRI |
|
TCA |
|
MAOI |
|
Other |
|
Although selective serotonin reuptake inhibitors (SSRIs) are a common initial choice in the treatment of major depressive disorder, many patients do not respond to them. This patient has already failed 2 trials of antidepressants from the same class (ie, the SSRIs escitalopram and sertraline), making it preferable to switch him to an antidepressant with a different mechanism of action. Because no antidepressant is clearly more effective than others, drug selection is based on factors such as safety, side effect profile, specific depressive symptoms, comorbidity, and personal and family history of antidepressant response.
Alternate first-line antidepressant medications include bupropion, mirtazapine, serotonin norepinephrine reuptake inhibitors, and serotonin modulators (eg, vortioxetine). Bupropion is a norepinephrine dopamine reuptake inhibitor with a distinct mechanism of action from SSRIs in that it has no serotonergic effects. It is activating, does not cause weight gain, and has no sexual side effects. It would be a preferred choice for this patient whose depressive symptoms include hypersomnia and weight gain.
(Choice A) Tricyclic antidepressants (eg, amitriptyline) are generally reserved for treatment-refractory patients (nonresponders to multiple and different classes of first-line antidepressants) due to their less favorable side effect profile and safety issues (eg, cardiotoxicity, lethality in overdose).
(Choices B and E) Aripiprazole and lithium have been used as augmentation strategies in patients with inadequate antidepressant response, but are not used as monotherapy for major depressive disorder.
(Choice D) Fluoxetine is another SSRI that would likely be ineffective in a patient who has not responded to 2 antidepressants with the same mechanism of action.
(Choice F) Mirtazapine is an option when switching, but its adverse effects of sedation and weight gain make it a less-preferred choice for this patient.
(Choice G) Quetiapine is a second-generation antipsychotic that is effective in bipolar depression but is not used as monotherapy in unipolar depression.
Educational objective:
Patients who do not respond to selective serotonin reuptake inhibitors may benefit from switching to another first-line antidepressant medication. The norepinephrine and dopamine reuptake inhibitor bupropion is an activating antidepressant with a favorable side effect profile (eg, no weight gain or sexual side effects), making it a good choice for patients with weight gain, hypersomnia, or sexual dysfunction.