How can I safely taper off bupropion (Wellbutrin) 300 mg extended‑release?

How to Safely Taper Off Wellbutrin 300mg ER

Bupropion (Wellbutrin) 300mg ER should be tapered gradually over 4-8 weeks by reducing the dose by 10% of the most recent dose every 1-2 weeks, with the option to slow to 10% per month for patients who have been on the medication long-term (≥1 year) or who experience withdrawal symptoms. 1

Recommended Tapering Schedule

Standard Taper (4-8 weeks)

• Reduce by 10% of the current dose every 1-2 weeks, which translates to approximately 30mg reductions initially from 300mg 1, 2
• After reaching 150mg, continue with 10% reductions of each subsequent dose (e.g., 150mg → 135mg → 120mg → 108mg, etc.) 2
• The final doses before complete cessation should be very small (potentially as low as 15-30mg) to prevent a large drop in drug effect when stopped 3

Slower Taper for Long-Term Users (≥1 year)

• For patients on bupropion for ≥1 year, reduce by 10% per month or slower, as this approach is better tolerated and reduces withdrawal symptoms 1, 2
• Each new dose should be 90% of the previous dose, not a straight-line reduction from the starting dose 1
• This slower approach may take 6-12 months or longer to complete 1

Why Hyperbolic (Exponential) Tapering Matters

• Linear tapers (e.g., 300mg → 200mg → 100mg → 0mg) create disproportionately large drops in drug effect at lower doses, which is why withdrawal symptoms often worsen as you approach zero 4, 3
• Hyperbolic tapering (reducing by a percentage of the current dose) maintains more consistent reductions in the drug's biological effect throughout the taper 4, 2
• Studies on antidepressants show that tapers over months down to very low doses are more successful than the traditional 2-4 week tapers recommended in older guidelines 4

Monitoring During the Taper

• Schedule follow-up appointments at least monthly to assess for withdrawal symptoms and mood changes 1
• Monitor specifically for: anxiety, irritability, insomnia, mood changes, fatigue, difficulty concentrating, and any return of depressive symptoms 5
• If withdrawal symptoms occur, return to the previous well-tolerated dose and attempt a slower reduction (e.g., 5% reductions instead of 10%) after symptoms stabilize 1, 5

Managing Withdrawal Symptoms

• Withdrawal symptoms from bupropion typically include anxiety, irritability, insomnia, mood instability, fatigue, and difficulty concentrating 5
• For insomnia during taper, consider trazodone as an adjunctive medication 1
• For anxiety symptoms, consider gabapentin or cognitive behavioral therapy 1
• Reassure patients that mild symptoms are usually transient and self-limiting, but more severe symptoms require slowing or pausing the taper 5

Critical Safety Principles

• Never abruptly discontinue bupropion, as this can precipitate severe withdrawal symptoms and rapid mood destabilization 1, 5
• Patient agreement and collaboration are essential—ensure the patient understands the plan, agrees with the pace, and knows they can request slower tapering if needed 1
• Do not set a fixed timeline—the taper must be adjusted based on individual response, not a predetermined schedule 1
• Do not abandon the patient if they struggle with the taper—consider pausing at a stable dose rather than pushing forward 1

Practical Dosing Challenges

• The major barrier to proper tapering is obtaining flexible low doses, particularly in the final steps when doses like 30mg, 20mg, or 15mg are needed 2
• Extended-release formulations cannot be split, so you may need to:
  • Switch to immediate-release bupropion tablets (which can be split or compounded into smaller doses) for the final taper stages 2
  • Work with a compounding pharmacy to create custom lower-dose capsules 2
  • Consider alternating doses (e.g., 150mg one day, 75mg the next) to achieve intermediate reductions, though this is less ideal for ER formulations

Special Considerations

• Patients with a history of depression require even slower tapering and close monitoring for return of depressive symptoms 1, 5
• If the patient was taking bupropion for smoking cessation or weight management (as part of naltrexone-bupropion ER), be aware that discontinuation may lead to return of nicotine cravings or weight gain 1
• Address underlying depression, anxiety, and insomnia before and during the taper to improve outcomes 1
• Incorporate non-pharmacological support such as cognitive behavioral therapy, exercise, and stress management techniques during the tapering process 1

Common Pitfalls to Avoid

• Tapering too quickly (faster than 10% every 1-2 weeks for standard cases, or 10% per month for long-term users) 1, 2
• Using linear dose reductions instead of percentage-based reductions 4, 2
• Stopping at a "therapeutic minimum" dose (e.g., 150mg) and then jumping to zero—the final reductions should go much lower 4, 3
• Mistaking withdrawal symptoms for relapse of depression and unnecessarily restarting full-dose treatment instead of slowing the taper 5
• Making "cold referrals" to other clinicians during the taper without ensuring they have agreed to accept the patient's care 1