What alternative antidepressant to switch to for a post-stroke patient, a [AGE]-year-old man, who is not responding to Wellbutrin (bupropion) for presumed post-stroke depression?

Switch to an SSRI or SNRI as First-Line Treatment

For a post-stroke patient not responding to Wellbutrin (bupropion), switch to an SSRI (sertraline preferred) or SNRI as the first-line alternative, since these are the guideline-recommended agents for post-stroke depression and bupropion is not a standard treatment for this condition. 1, 2

Why Bupropion Is Not Appropriate for Post-Stroke Depression

• Bupropion is not mentioned in any major stroke guidelines as a recommended treatment for post-stroke depression 1, 2
• The American College of Physicians and American Heart Association explicitly recommend SSRIs and SNRIs as first-line pharmacological treatments for post-stroke depression 1, 2
• The lack of response may reflect that bupropion was not the optimal choice from the outset rather than true treatment resistance 1

Recommended Switch Strategy

Switch to sertraline as the optimal first-line choice:

• Start sertraline 50 mg daily, with titration to 100-200 mg daily based on clinical response over 2-4 weeks 1
• Sertraline has the most robust evidence in post-stroke depression with proven efficacy and safety 3, 4
• Sertraline has a lower risk of QTc prolongation compared to citalopram or escitalopram, which is critical in stroke patients who may have underlying cardiac conduction abnormalities 1, 3
• Continue treatment for at least 6 weeks to assess full antidepressant effect 1

Alternative SSRI Options If Sertraline Not Tolerated

• Citalopram (20-40 mg daily) or escitalopram (10-20 mg daily) are acceptable alternatives 3
• Monitor QTc interval more carefully with these agents due to higher risk of prolongation 1, 3
• Paroxetine and fluoxetine also have evidence for efficacy in post-stroke depression 2, 5

Consider SNRIs in Specific Clinical Scenarios

Switch to an SNRI (duloxetine or venlafaxine) if the patient has:

• Comorbid central post-stroke pain requiring dual serotonin-norepinephrine action 6, 2, 3
• Duloxetine is specifically recommended as second-line treatment for central post-stroke pain 6
• Venlafaxine 37.5-225 mg daily can address both depression and neuropathic pain 3

Avoid Tricyclic Antidepressants in This Population

• TCAs should be avoided in stroke patients because they can provoke orthostatic hypotension, worsening of heart failure, and arrhythmias 1
• While TCAs are effective for post-stroke depression, they have more side effects than SSRIs and should be used with caution in elderly patients due to anticholinergic effects 2

Add Cognitive Behavioral Therapy

Combine pharmacotherapy with CBT for optimal outcomes:

• Cognitive behavioral therapy is recommended as an effective treatment for post-stroke depression 1, 2
• The combination of pharmacotherapy and CBT may enhance outcomes, though evidence for superiority of combination therapy over monotherapy is limited 1

Monitoring and Duration

• Use validated screening tools like PHQ-9 at baseline and every 2-4 weeks to objectively track response 2, 3
• Continue treatment for at least 6 months after achieving remission 2, 3
• Monitor for hyponatremia, particularly in the first few weeks, as elderly patients are at higher risk for SSRI-induced SIADH 3
• Watch for QTc interval prolongation, which can predispose to ventricular tachycardia 1

Common Pitfalls to Avoid

• Screen for and treat comorbid anxiety disorders, which frequently coexist with post-stroke depression and may require dose adjustment 1, 2
• Use SSRIs with caution in patients with a history of intracerebral hemorrhage due to a small increased risk of rebleeding 1
• Never use antidepressants prophylactically in non-depressed stroke patients due to risk of fractures and other adverse events 1, 3