A 60-year-old man presents to his primary care physician with weight gain. He states that ever since his wife died 4 months ago, he has been eating and sleeping more and no longer engages in any activities he once enjoyed such as hiking or fishing. He feels guilty for not spending more time with his wife before she died. He was recently fired for making several major bookkeeping mistakes at work as an accountant as he had trouble focusing. The patient is requesting oxycodone at this appointment as he states he has burning pain in his legs that feels worse now than it has in years past. The patient has a past medical history of obesity, poorly controlled diabetes, hypertension, and peripheral vascular disease. His temperature is 98.7°F (37.1°C), blood pressure is 129/82 mmHg, pulse is 83/min, respirations are 15/min, and oxygen saturation is 99% on room air. Physical exam reveals a stable gait and reduced sensation symmetrically over the lower extremities. He complains of electric pain when touching his lower extremities. His affect seems depressed. Which of the following is the most appropriate treatment for this patient?
Venlafaxine
Bupropion
Amitriptyline
Escitalopram
Venlafaxine
This patient is presenting with sleep changes, interest loss, guilt, decrease in energy, and trouble concentrating for greater than 2 weeks concerning for major depressive disorder. In the setting of his diabetic neuropathy (lower extremity burning pain in the setting of poorly managed diabetes), a serotonin-norepinephrine reuptake inhibitor (SNRI) such as venlafaxine is the most appropriate initial treatment for this patient.

Major depressive disorder should always initially be managed with cognitive behavioral therapy and often medication. Typically, the first-line medication is a selective serotonin reuptake inhibitor (SSRI). However, SNRIs such as venlafaxine and duloxetine are viable first-line options. They are particularly preferred in patients with diabetic neuropathy as they treat both diabetic neuropathy and depression. SNRIs are also generally considered to be less sedating than SSRIs. For this reason, SNRIs are often a better initial drug in depression than SSRIs in diabetic patients with peripheral neuropathy.

Sansone and Sansone discuss SNRIs and their uses. They discuss how there are different efficacies and propensities of the different SNRIs. They recommend choosing an appropriate SNRI based on the patient's needs and comorbidities.

Incorrect Answers:
Answer A: Amitriptyline is a tricyclic antidepressant that can be used to treat depression in patients who also suffer from other neuropathic pain conditions or conditions such as fibromyalgia or irritable bowel syndrome. While it may also be used in diabetic neuropathy and depression, there is higher toxicity with this medication than SNRIs. For this reason, SNRIs are preferred. A TCA might be appropriate if the patient had already failed other first-line agents.

Answer B: Bupropion is a weight-neutral antidepressant that can be used in smoking cessation and patients who are trying to avoid the sexual side effects of SSRIs (anorgasmia). It would not address this patient's diabetic neuropathy, though it could be beneficial for his obesity.

Answer C: Escitalopram is an SSRI that could be used first-line for major depressive disorder. However, if a patient has a concomitant condition, it is better to choose a single agent that addresses both problems; thus, SNRIs are better first-line medications in this patient with diabetic neuropathy.

Answer D: Phenelzine is a monoamine oxidase inhibitor that can be used in atypical depression or as a third-line or later agent in the management of depression. This agent can cause a hypertensive crisis in the setting of tyramine consumption, has many medication interactions, and a long washout period. Thus, it is not usually a first or second-line agent. However, it is highly effective in patients who have failed other first-line agents and should still be used in appropriate candidates.

Bullet Summary:
SNRIs are appropriate first-line agents for major depressive disorder in patients with diabetic neuropathy.