What alternative medications can be used to manage anxiety and insomnia in a patient taking Wellbutrin XL (Bupropion) 150mg daily, with a history of serotonin syndrome and intolerance to SSRIs (Selective Serotonin Reuptake Inhibitors), and who cannot take controlled substances?

Management of Anxiety and Insomnia in a Patient on Bupropion with SSRI Intolerance

For this patient with anxiety and insomnia who is currently on Wellbutrin XL, has a history of serotonin syndrome with SSRIs, and cannot take controlled substances, trazodone at a low dose (25-50mg) at bedtime is the most appropriate medication to add to his regimen.

Medication Analysis and Recommendation

Current Medication Issues

• Bupropion (Wellbutrin XL) 150mg daily is likely contributing to anxiety and insomnia
• Patient has history of serotonin syndrome with sertraline
• Poor response to fluoxetine and buspirone (caused agitation)
• Hydroxyzine 50mg at bedtime is not effective for sleep
• Propranolol 40mg TID for essential tremor

First-Line Recommendation

1. Add trazodone 25-50mg at bedtime

   • Trazodone is effective for insomnia at low doses (25-100mg) 1
   • Has minimal serotonergic activity at these doses, reducing risk of serotonin syndrome 2
   • Not a controlled substance
   • FDA-approved dosing starts at 150mg/day for depression, but lower doses are commonly used off-label for insomnia 1, 3

2. Adjust administration of current medications

   • Consider taking Wellbutrin XL earlier in the morning to minimize insomnia effects 4
   • Wellbutrin should not be given after 3pm to minimize risk of insomnia 4

Rationale for Trazodone Selection

Trazodone is particularly appropriate for this patient because:

• It effectively treats both insomnia and anxiety at low doses 3
• It's not a controlled substance
• It has a different mechanism than SSRIs, which the patient cannot tolerate
• It's commonly used off-label for insomnia 3
• At low doses (25-50mg), the risk of serotonin syndrome when combined with bupropion is minimized 2

Potential Alternatives

If trazodone is not effective or not tolerated:

1. Mirtazapine 7.5-15mg at bedtime

   • Promotes sleep, appetite, and weight gain 4
   • Well-tolerated at low doses
   • Not a controlled substance
   • Initial dose: 7.5mg at bedtime, maximum 30mg 4

2. Nortriptyline 10-25mg at bedtime

   • Useful for patients with agitated depression and insomnia 4
   • Sedating but has less cardiotoxic and anticholinergic effects than other TCAs
   • Initial dose: 10mg at bedtime, maximum 40mg per day 4

Important Precautions

Risk of Serotonin Syndrome

• While combining bupropion and trazodone carries some risk of serotonin syndrome, this risk is minimized at low doses of trazodone used for insomnia 5, 6
• Monitor for signs of serotonin syndrome: mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms 1
• Start with the lowest effective dose (25mg) and titrate slowly if needed

Cardiac Considerations

• Trazodone may cause orthostatic hypotension, which could interact with propranolol 1
• Monitor blood pressure during initial titration
• Rare risk of cardiac arrhythmias, especially in patients with pre-existing cardiac disease 1

Non-Pharmacological Recommendations

In addition to medication:

• Implement consistent sleep hygiene practices 7:

  • Maintain stable bed and wake times
  • Avoid daytime napping (limit to 30 minutes if needed, not after 2pm)
  • Avoid caffeine, nicotine, and alcohol
  • Avoid heavy exercise within 2 hours of bedtime
  • Use the bedroom only for sleep and sex
  • Leave the bedroom if unable to fall asleep within 20 minutes

• Consider relaxation techniques 7:

  • Progressive muscle relaxation
  • Guided imagery
  • Diaphragmatic breathing
  • Meditation

Follow-Up Plan

• Reassess in 2 weeks after starting trazodone
• If insomnia persists, consider increasing trazodone dose gradually (up to 100mg)
• If anxiety remains problematic, consider alternative non-SSRI, non-controlled options