What are the effects of Wellbutrin (bupropion) on the nigrostriatal pathway in patients with Parkinson's disease or those at risk of developing it?

Bupropion's Effects on the Nigrostriatal Pathway

Bupropion (Wellbutrin) binds to and occupies dopamine transporters (DAT) in the nigrostriatal pathway, which can interfere with dopamine transporter imaging used to diagnose Parkinson's disease, but does not appear to cause clinically significant nigrostriatal damage or worsen Parkinsonism in most patients. 1, 2

Mechanism of Action on Dopamine Transporters

Bupropion functions as a norepinephrine-dopamine reuptake inhibitor (NDRI) with documented effects on striatal dopamine transporters 3, 2:

• Bupropion demonstrates weak but measurable dopamine transporter occupancy in the striatum, which includes the putamen and caudate nucleus—key components of the nigrostriatal pathway 1, 2
• The drug's binding to DAT can persist longer than expected, with effects potentially lasting beyond the standard 1-week washout period typically recommended before dopamine transporter imaging 1
• One case report documented that DAT binding ratios increased by 5.2% to 31.7% across all striatal regions when bupropion was discontinued for one month versus one week, demonstrating prolonged occupancy 1

Clinical Implications for Parkinson's Disease Patients

Potential Therapeutic Benefits

Bupropion may provide mild antiparkinsonian effects in some patients, though evidence is limited and mixed 4:

• In a study of 20 patients with idiopathic Parkinson's disease, parkinsonism symptoms lessened by at least 30% in half the patients treated with bupropion 4
• The mechanism is thought to involve indirect dopaminergic agonist activity, without significant anticholinergic or MAO inhibitor effects 4
• Bupropion has been proposed as a first-line treatment for depression in PD patients specifically because of its dopaminergic and noradrenergic activity, which theoretically could address both depressive symptoms and motor deficits 3

Important Caveats and Limitations

Side effects were frequent and dose-limiting in 25% of patients (5 of 20) in the primary efficacy study, suggesting tolerability concerns 4:

• Depression improved in only 5 of 12 patients with comorbid depression and PD, indicating variable antidepressant efficacy in this population 4
• Case reports document successful treatment of depression in PD with bupropion, but no controlled double-blind studies have been conducted, requiring caution when prescribing 5
• One case report described a 78-year-old female whose motor abilities improved on levodopa and depression improved with bupropion after other antidepressants failed 5

Critical Diagnostic Interference

Bupropion causes false-positive results on dopamine transporter imaging (DaTscan/SPECT), potentially leading to misdiagnosis of Parkinson's disease 1, 2:

• A 52-year-old man on 150 mg/day bupropion showed abnormal DAT imaging after the standard 1-week discontinuation, with specific binding ratios indicating apparent nigrostriatal dysfunction 1
• Repeat imaging after 1-month discontinuation normalized completely, with no levodopa response or other features supporting neurodegenerative parkinsonism 1
• A 66-year-old male with MDD and hand tremors showed decreased DAT binding capacity bilaterally on Tc-99m TRODAT-1 SPECT while taking bupropion 150 mg/day, which improved after 14 days of discontinuation 2

Practical Recommendations for Imaging

When dopamine transporter imaging is planned in patients taking bupropion, discontinue the medication for at least one month before scanning 1:

• The standard 1-week washout (5 plasma half-lives) is insufficient to clear bupropion's effects on DAT binding 1
• If imaging results contradict clinical presentation, consider longer medication washout and rescan before initiating anti-Parkinson's medications 1
• All drugs that alter DAT occupancy should be carefully assessed when interpreting dopamine transporter imaging 2

Relationship to Nigrostriatal Dysfunction in Related Conditions

The evidence documents dopaminergic dysfunction in the nigrostriatal pathway in related conditions, providing context 6:

• PET and SPECT scans demonstrate dysfunction in dopaminergic nigrostriatal systems in patients with REM sleep behavior disorder (RBD), which often precedes Parkinson's disease 6
• Decreased striatal dopamine transporters have been documented in patients with RBD, with correlation between decreased striatal binding and severity of motor symptoms 6
• This suggests the nigrostriatal pathway is vulnerable in neurodegenerative conditions, making drug effects on this system clinically relevant 6

Bottom Line for Clinical Practice

Bupropion occupies dopamine transporters in the nigrostriatal pathway but does not cause permanent damage or consistently worsen Parkinsonism 4, 1, 2. The primary clinical concern is diagnostic interference with dopamine transporter imaging, requiring extended medication washout (one month rather than one week) before scanning 1. While bupropion may provide mild symptomatic benefit in some PD patients, the lack of controlled trials and frequent side effects limit its role as a primary antiparkinsonian agent 5, 4.