A 55-year-old man presents to his primary care physician with persistent symptoms of depression. He started taking fluoxetine 3 weeks ago when he was diagnosed with major depressive disorder after a divorce. Since then, he notes that his symptoms are roughly unchanged. His other medications include albuterol. His temperature is 99.3°F (37.4°C), blood pressure is 132/88 mmHg, pulse is 77/min, respirations are 14/min, and oxygen saturation is 99% on room air. Physical exam reveals a depressed affect. His neurologic exam is non-focal. A serum thyroid stimulating hormone (TSH) resulted from his last visit and is noted to be 4.8 µU/mL (normal: 0.5-5 µU/mL). Which of the following is the most appropriate next step in management?
Change medication to bupropion
Increase dose of current medication
Maintain dose of current medication
Change medication to escitalopram
Maintain dose of current medication
This patient is presenting with major depressive disorder but has not given his current selective serotonin reuptake inhibitor (SSRI) at least 4 weeks to begin working. Thus, he should be reassured and maintained on the current dose of his SSRI, with follow-up after the 4 week mark to see if his symptoms have improved.

Major depressive disorder is managed initially with cognitive behavioral therapy and pharmacotherapy. The typical first-line medication is an SSRI. SSRIs may take at least 4 weeks or more to begin working, so patients that return before this time period should be reassured and encouraged to let the medication take effect as long as they are not experiencing suicidal thoughts or intent. If the medication is not working after at least 4 weeks, the next steps in management could include increasing the dose of the current medication, changing SSRIs, adding another antidepressant agent, or adding a low dose of levothyroxine. All patients with suicidal ideation and either intent or a plan to hurt themselves should be hospitalized involuntarily.

Gautam et al. discuss the current management algorithms for major depressive disorder. They note different options including CBT and pharmacotherapy. They recommend appropriate treatment with a first-line agent based on the patient and their circumstances.

Incorrect Answers:
Answer A: Administering levothyroxine is appropriate as an augmenting agent in patients who do not have an improvement in symptoms on SSRIs or other antidepressants even if their TSH is within the normal range. However, it would not be attempted at this point given this patient has not given his current medication sufficient time to begin working. There is limited evidence to support its use overall. Note that this patient's TSH is within normal limits. In some cases, T3 administration is used in refractory depression.

Answer B: Changing the medication to bupropion could be appropriate in patients who want to avoid weight gain, those who want to quit smoking, or those who are trying to avoid sexual side effects. It also is an appropriate second-line agent or could be added to a first-line agent; however, this patient’s current medication should be tried for at least 4 weeks before changing medications.

Answers 3 & 4: Changing medication to escitalopram or increasing the dose of the current medication are both viable strategies if a patient has failed to improve on their first medication after at least 4 weeks on the medication. Increasing the dose early may lead to symptoms of serotonin excess when the drug takes effect.

Bullet Summary:
SSRIs are the first-line agents in the management of major depressive disorder and should be tried for at least 4 weeks before changing the treatment regimen.