A 31-year-old woman comes to the office for follow-up treatment of major depressive disorder. Five months ago, the patient attempted suicide by hanging after learning that her husband had filed for divorce. She was admitted to a psychiatric unit, where she was treated with fluoxetine 20 mg and discharged 2 months later. A month following discharge, the fluoxetine dosage was increased. The patient now says that her suicide attempt was "stupid" and denies suicidal ideation. However, despite taking maximum doses of fluoxetine for 8 weeks, she still feels very depressed and reports minimal improvement in her energy level, motivation, and concentration. The patient has ongoing feelings of guilt regarding the impact of her suicide attempt on her mother and young children. Other medical conditions include a history of bulimia nervosa and allergic rhinitis. Family history is significant for bipolar disorder in her mother. Mental status examination reveals poor eye contact, constricted affect, and soft speech. Which of the following is the most appropriate next step in the pharmacologic management of this patient's depression?
The selective serotonin reuptake inhibitor (SSRI) fluoxetine has failed as an initial treatment in this patient with major depressive disorder. Although she is no longer suicidal, her persistent and impairing depressive symptoms require pharmacologic treatment. Continuing fluoxetine for an additional 4 weeks (Choice A) is not indicated because the patient has already had an adequate trial (adequate dose and duration ≥6 weeks). Patients with minimal to no improvement with initial antidepressant treatment should be switched to another antidepressant.
Options include a different SSRI or another first-line antidepressant with a different mechanism of action, such as a serotonin-norepinephrine reuptake inhibitor (eg, venlafaxine). Other first-line antidepressant options include bupropion, mirtazapine, or serotonin modulators (eg, vilazodone). However, bupropion would be contraindicated in this patient due to her history of bulimia nervosa; the risk of seizures increases in patients with active or historical bulimia or anorexia nervosa because of potential electrolyte disturbances (Choice D).
(Choice B) Electroconvulsive therapy is generally indicated for patients with very severe depressive symptoms (eg, persistent suicidality, malnutrition/dehydration), major depression with psychotic features, or failure to respond to multiple medication trials.
(Choice C) The mood stabilizer lithium can be added to augment an antidepressant for the treatment of unipolar depression but is not used as monotherapy.
(Choices E and F) Tricyclic antidepressants (eg, nortriptyline) and monoamine oxidase inhibitors (MAOIs) (eg, phenelzine) are not first-line antidepressants because of poor tolerability and concerns about safety (ie, cardiotoxicity with tricyclics, risk of hypertensive crisis with MAOIs). These medications are generally reserved for patients in whom several trials of first-line antidepressants have failed. Switching from fluoxetine to an MAOI would also require a 5-week washout period due to the long half-life of fluoxetine (in contrast, washout is 2 weeks for other antidepressants).
Educational objective:
When major depression fails to respond to an initial selective serotonin reuptake inhibitor (SSRI) trial, patients should be switched to another first-line antidepressant. Options include a different SSRI, a serotonin-norepinephrine reuptake inhibitor, bupropion, mirtazapine, or serotonin modulators.