What are the considerations for using Wellbutrin (bupropion) to treat depression in patients with Multiple Sclerosis (MS)?

Bupropion (Wellbutrin) for Depression in Multiple Sclerosis

Bupropion is a reasonable antidepressant option for treating depression in MS patients, with efficacy comparable to other second-generation antidepressants (SGAs), though SSRIs like sertraline remain the preferred first-line choice. 1

Evidence for Efficacy

• Bupropion demonstrates equivalent efficacy to other SGAs (sertraline, venlafaxine) for major depressive disorder, with moderate-quality evidence showing no significant differences in response or remission rates when switching between these agents 1

• When used as augmentation therapy with citalopram, bupropion decreases depression severity more effectively than buspirone, though response and remission rates are similar 1

• At 300 mg daily, bupropion has demonstrated effectiveness for long-term treatment of recurrent major depression 1

• Bupropion may be particularly beneficial for MS patients with comorbid depression who also smoke, as it has proven efficacy for smoking cessation (OR 2.07 vs placebo) 1

MS-Specific Considerations

First-Line Treatment Preference

• SSRIs, particularly sertraline, remain the preferred first-line antidepressant in MS patients 2
  • Start sertraline at 25 mg/day, increase to 50 mg/day, with maximum of 200 mg/day 2
  • Paroxetine is the second-choice SSRI, starting at 10 mg/day for 5 days, then 20 mg/day (maximum 50 mg/day) 2

When to Consider Bupropion

• Bupropion should be considered as a second-line option after SSRI failure or as augmentation therapy 1

• Prioritize bupropion in MS patients with:

  • Comorbid smoking who need cessation assistance 1
  • Sexual dysfunction concerns (bupropion has minimal sexual side effects compared to SSRIs) 3
  • Fatigue as a prominent symptom (bupropion's activating properties may be beneficial) 3

Critical Safety Concerns in MS

Seizure Risk - The Primary Contraindication

• Bupropion lowers the seizure threshold and carries a 0.1% seizure risk at therapeutic doses 1

• Absolute contraindications in MS patients: 1

  • History of seizures or epilepsy
  • Brain metastases or lesions with elevated seizure risk
  • Factors that increase seizure threshold (common in MS due to demyelinating lesions)

• Maximum dose must not exceed 450 mg/day in divided doses to minimize seizure risk 4

Other Safety Considerations

• Monitor blood pressure and heart rate, especially in first 12 weeks, as bupropion can cause hypertension 1

• Avoid in patients requiring opioid therapy (if using naltrexone-bupropion combination) 1

• Discontinue at least 14 days before using MAO inhibitors 1

• Common side effects include dry mouth, disturbed sleep, headaches, and nausea 1

Dosing and Monitoring

• Neuropsychiatric adverse effects require monitoring, particularly suicidal thoughts in patients under 24 years 1

• Discontinuation due to adverse events is lower with bupropion compared to buspirone (moderate-quality evidence) 1

Critical Gap in Evidence

• Depression remains severely undertreated in MS patients managed by neurologists, with 65.6% of those with major depressive disorder receiving no antidepressant medication 5

• Only two small trials (70 total participants) have specifically studied antidepressants in MS patients, neither involving bupropion directly 6

• The Cochrane review found insufficient evidence to make definitive recommendations about specific antidepressants in MS, highlighting the need for head-to-head trials 6

Practical Algorithm

1. Screen all MS patients for depression (25.8% prevalence of MDD in MS) 5

2. First-line: Start SSRI (sertraline preferred) 2

3. Consider bupropion if:

   • SSRI fails or causes intolerable side effects 1
   • Patient smokes and needs cessation support 1
   • Sexual dysfunction is problematic 3
   • BUT ONLY if no seizure history or risk factors 1

4. Combine with cognitive behavioral therapy or mindfulness-based interventions for optimal outcomes 2