Why did tapering off bupropion (Wellbutrin) 300 mg and initiating duloxetine (Cymbalta) for fibromyalgia markedly worsen my restless legs syndrome despite being on gabapentin 800 mg daily and ropinirole extended‑release 4 mg?

Why Switching from Bupropion to Duloxetine Worsened Your RLS

Duloxetine (Cymbalta) is a serotonergic antidepressant that directly exacerbates restless legs syndrome, and you are already experiencing augmentation from ropinirole—a dopamine agonist that paradoxically worsens RLS with chronic use—making your current regimen fundamentally flawed despite the gabapentin. 1

The Core Problem: Serotonergic Medications Worsen RLS

• The American Academy of Sleep Medicine explicitly recommends avoiding serotonergic medications as they are known exacerbating factors for RLS 1
• Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that increases serotonin activity, which directly antagonizes the dopaminergic pathways that regulate RLS symptoms 1
• Bupropion, in contrast, does not increase serotonin and actually modulates dopaminergic systems through dopamine and norepinephrine reuptake inhibition 2
• Multiple case reports and one randomized controlled trial demonstrate that bupropion improves RLS symptoms, with one study showing a 10.8-point reduction in International RLS Study Group severity scores at 3 weeks compared to 6.0 points with placebo 3, 4, 2
• The American Academy of Sleep Medicine specifically recommends against bupropion for RLS treatment (conditional recommendation, moderate certainty), but this is based on insufficient evidence for its use as primary RLS therapy—not because it worsens symptoms 1

The Augmentation Crisis: Your Ropinirole is Making Things Worse

• You are almost certainly experiencing augmentation from ropinirole 4 mg XR, which manifests as earlier symptom onset during the day, increased intensity, and spread to other body parts 1, 5, 6
• The American Academy of Sleep Medicine suggests against the standard use of ropinirole due to a 7–10% annual risk of augmentation (conditional recommendation, moderate certainty of evidence) 1, 5
• Dopamine agonists like ropinirole are no longer first-line therapy as of the 2025 American Academy of Sleep Medicine guidelines, superseding older 2012 recommendations 1, 7
• Do not increase your ropinirole dose—this will worsen augmentation 1, 5

Why Gabapentin 800 mg Daily is Insufficient

• Your gabapentin dose of 800 mg daily is far below the therapeutic range for RLS 1
• The American Academy of Sleep Medicine recommends starting gabapentin at 300 mg three times daily (900 mg/day total) and titrating to a maintenance dose of 1800–2400 mg/day divided three times daily, with maximum studied doses up to 3600 mg/day 1
• Single nighttime dosing fails to address daytime RLS symptoms and provides suboptimal 24-hour coverage 1
• At 800 mg daily, you are receiving only 33–44% of the minimum recommended therapeutic dose 1

The Correct Treatment Algorithm

Immediate Actions (Next 1–2 Weeks)

1. Stop duloxetine and restart bupropion 300 mg, as bupropion does not worsen RLS and may actually improve symptoms 1, 3, 4, 2
2. Increase gabapentin to 300 mg three times daily (900 mg/day), then titrate by 300 mg every 3–7 days to reach 1800–2400 mg/day divided three times daily 1
3. Check morning fasting ferritin and transferrin saturation after withholding iron supplements for ≥24 hours; if ferritin ≤75 ng/mL or transferrin saturation <20%, add iron supplementation 1

Transition Off Ropinirole (Weeks 2–8)

• Add gabapentin to therapeutic doses (1800–2400 mg/day) BEFORE tapering ropinirole to prevent rebound symptoms 1, 6
• Once symptom control is achieved with gabapentin, down-titrate ropinirole very slowly by 0.25 mg every 1–2 weeks 1, 6
• Anticipate rebound RLS and insomnia during the taper; short-acting opioids or clonidine may be used temporarily as bridge therapy 1
• For severe augmentation, consider bypassing gabapentin titration and transitioning directly to an opioid (extended-release oxycodone 5–10 mg at bedtime) 1

Alternative First-Line Options

• Pregabalin is strongly recommended as first-line therapy (strong recommendation, moderate certainty) and allows twice-daily dosing with superior bioavailability compared to regular gabapentin 1
  • Starting dose: 50 mg three times daily or 75 mg twice daily 1
  • Titrate to 300 mg/day after 3–7 days, then increase by 150 mg every 3–7 days as tolerated 1
  • Maximum dose: 600 mg/day 1

Critical Pitfalls to Avoid

• Do not continue duloxetine—it is fundamentally incompatible with RLS management 1
• Do not increase ropinirole—this will worsen augmentation 1, 5
• Do not use gabapentin 800 mg daily as monotherapy—this is a subtherapeutic dose 1
• Do not assume your iron status is adequate without checking ferritin and transferrin saturation using RLS-specific thresholds (≤75 ng/mL, not the general population threshold) 1

Why This Happened

Your physician likely prescribed duloxetine for fibromyalgia without recognizing that serotonergic medications are contraindicated in RLS 1. The combination of adding a serotonergic drug (duloxetine) while removing a dopaminergic drug (bupropion) created a perfect storm, compounded by pre-existing augmentation from ropinirole and subtherapeutic gabapentin dosing 1, 6.