What medications can be added to Wellbutrin (bupropion) for a patient complaining of fatigue and insomnia?

Medications to Add to Wellbutrin for Fatigue and Insomnia

For patients on Wellbutrin (bupropion) experiencing both fatigue and insomnia, mirtazapine (Remeron) at a low dose of 7.5-15mg at bedtime is the most appropriate medication to add, as it promotes sleep while addressing fatigue through its dual action mechanism.

Understanding the Paradox

Wellbutrin (bupropion) presents a therapeutic challenge in this scenario:

• Bupropion is activating and can improve energy levels 1
• However, it commonly causes insomnia as a side effect 2
• When taken too late in the day, bupropion can worsen insomnia 1

First-Line Addition: Mirtazapine

Mirtazapine is the optimal choice for several reasons:

• Promotes sleep: Potent sedative effects at lower doses (7.5-30mg) 1, 3
• Addresses fatigue: Helps with energy levels during the day 1
• Well-tolerated: Guidelines note it is "potent and well tolerated" 1
• Complementary mechanism: Works through different neurotransmitter systems than bupropion
• Starting dose: 7.5mg at bedtime, can be increased to 15-30mg if needed 1

Alternative Options Based on Symptom Predominance

If insomnia is the predominant concern:

1. Trazodone:

   • Effective for antidepressant-associated insomnia 4
   • Low dose (25-100mg) at bedtime
   • 67% of patients experienced improvement in sleep when added to regimens including bupropion 4
   • Less activating than other options

2. Nortriptyline:

   • More sedating than other tricyclics 1
   • Useful for patients with agitated depression and insomnia
   • Starting dose: 10mg at bedtime 1
   • Monitor for anticholinergic side effects

If fatigue is the predominant concern:

1. Modafinil/Armodafinil:
   • Modest efficacy for cancer-related fatigue 1
   • Most effective for severe fatigue
   • Take in the morning to avoid worsening insomnia

Practical Recommendations

1. Timing of bupropion doses:

   • Ensure the second dose of bupropion is taken before 3 p.m. to minimize insomnia risk 1
   • Maximum recommended dose is 150mg twice daily 1

2. Non-pharmacological approaches:

   • Implement sleep hygiene measures 3
   • Consider cognitive behavioral therapy for insomnia (CBT-I) 1, 3
   • Regular physical activity during daytime hours 3

3. Monitoring and follow-up:

   • Assess response within 2-4 weeks 3
   • Monitor for side effects, particularly excessive daytime sedation
   • Adjust dosing based on response

Important Caveats

• Avoid benzodiazepines in elderly patients or those with cognitive impairment 1
• Mirtazapine may cause weight gain, which could be beneficial in underweight patients 1
• A full therapeutic trial of any antidepressant requires 4-8 weeks 1
• If symptoms persist despite medication adjustments, consider referral to a sleep specialist 3

Dosing Algorithm

1. Start mirtazapine at 7.5mg at bedtime
2. After 1-2 weeks, assess response:
   • If improved but inadequate: increase to 15mg at bedtime
   • If no improvement: increase to 15mg at bedtime or consider alternative agent
3. Maximum dose: 30mg at bedtime 1
4. Ensure bupropion is dosed appropriately (second dose before 3pm)