A 49-year-old woman comes to the office due to depression. She quit her retail sales job 6 months ago because she could no longer stand all day due to increasing numbness, tingling, and painful, burning sensations in her feet. The patient has since become increasingly depressed, withdrawn, and preoccupied, with feelings of low self-esteem. She has a low level of energy, is unable to concentrate to read or watch television, and has lost interest in family and friends. Medical history is significant for obesity, hypercholesterolemia, and long-standing type 2 diabetes mellitus. Medications include metformin, liraglutide, and rosuvastatin. The patient has no prior psychiatric history. After medical evaluation, major depressive disorder is diagnosed. Which of the following is the most appropriate pharmacotherapy for treating this patient's condition?
This patient with long-standing type 2 diabetes mellitus has major depression and diabetic peripheral neuropathy, a distressing and disabling complication that contributes to depression and poor quality of life.
First-line analgesics for neuropathic pain (eg, diabetic peripheral neuropathy) include the following:
These medications act on nociceptors and neurotransmitters and thereby decrease pain transmission.
The choice of medication depends on comorbid conditions. Gabapentinoids are best prescribed for patients with neuropathic pain and focal seizure disorder. SNRIs and TCAs are ideally used in patients with neuropathic pain and comorbid depression. However, TCAs are less commonly prescribed than SNRIs because of more serious adverse effects (eg, cardiotoxicity, QT prolongation, orthostatic hypotension, urinary retention). In this patient, duloxetine is an ideal choice because it is a first-line analgesic for neuropathic pain that also treats major depressive disorder.
(Choice A) Bupropion is a norepinephrine-dopamine reuptake inhibitor that has not demonstrated efficacy in relieving neuropathic pain. It is associated with an increased risk for seizures but with less weight gain and fewer sexual adverse effects than selective serotonin reuptake inhibitors (SSRIs).
(Choice B) Citalopram is an SSRI used to treat major depressive disorder; however, compared to SNRIs, SSRIs have weaker evidence for the treatment of neuropathic pain.
(Choice D) Mirtazapine is an antidepressant that increases norepinephrine and serotonin release by inhibiting central alpha-2 adrenergic receptors. It is typically used in patients with insomnia and weight loss due to its sedating and appetite-stimulating properties. It does not treat neuropathic pain and should be avoided in patients with obesity.
(Choice E) Trazodone is a serotonin modulator that is highly sedating and commonly used in lower doses for insomnia. It does not treat neuropathic pain and can cause orthostatic hypotension, as well as priapism in men.
Educational objective:
Serotonin-norepinephrine reuptake inhibitors (eg, duloxetine) have analgesic properties that can be helpful in treating patients with comorbid depression and chronic neuropathic pain, including painful diabetic neuropathy.