The study aimed to identify peripheral neuropathy (PN) in Parkinson’s disease (PD) or Parkinsonism syndrome patients on long-term carbidopa/levodopa compared to those not on carbidopa/levodopa therapy. 

Carbidopa/levodopa is the primary therapeutic option for PD, but its long-term consequences remain poorly defined in the literature. PD patients are predisposed to developing PN due to the pathophysiology of the disease. Chronic carbidopa/levodopa therapy may exacerbate PN, but its association still remains unclear. 

This retrospective study extracted de-identified data from 203 patients evaluated at a neurology clinic between 2011-2025 with diagnoses of PD or Parkinsonism syndromes (mean age 68.6 years; 76.8% PD, 23.2% Parkinsonism). Patient’s on carbidopa/levodopa were included if they had been treated with it for ≥ 2 years with no prior use. Patients with history of PN or comorbidities inducing PN were excluded.  

A logistic regression analysis was performed to determine the effects of age, sex, diagnosis (PD vs Parkinsonism), and carbidopa/levodopa exposure on the probability of having peripheral neuropathy. Among the participants, those on carbidopa/Levodopa were 11.32 (95% CI: 2.60-49.27, p=0.001) more likely of having peripheral neuropathy compared to those who are not while controlling for Parkinson/Parkinsonism. There were no statistically significant associations found with respect to age (OR=1.04, 95 CI% 0.99-1.08, p=0.117) and sex (OR=0.88, 95 CI% 0.46-1.69, p=0.707).

Chronic carbidopa/levodopa therapy is significantly associated with PD/Parkinsonism patients and PN development. This finding reinforces the importance of identifying risk factors contributing to PN in this patient population. Levodopa use can induce B-vitamin deficiency (B12, B9, B6) worsening PN development. Clinicians can alter medical management to include routine monitoring of vitamin panels and related metabolites (methylmalonic acid, homocysteine). This can increase early detection of reversible deficiencies through supplementation and reduce PN burden and improve patient outcomes.