Efficacy and Safety of Nicotine-Based Interventions in Parkinson's Disease: A Systematic Review and Meta-Analysis

<jats:p>Background: Nicotine has been proposed as a potential therapeutic agent in Parkinson's disease (PD) based on epidemiologic and preclinical evidence, but clinical findings remain inconsistent. This systematic review and meta-analysis evaluated the efficacy and safety of nicotine-based interventions in PD. Methods: Randomized controlled trials comparing nicotine-based interventions with placebo or control in patients with PD were systematically reviewed. Outcomes included motor severity, activities of daily living, quality of life (QoL), levodopa equivalent daily dose (LEDD), and adverse events. Random-effects meta-analyses were performed, and certainty of evidence was evaluated using the GRADE framework (PROSPERO CRD420261442440). Results: Six randomized trials involving 389 participants were included. Nicotine did not significantly improve motor outcomes (SMD −0.16, 95% CI −0.76 to 0.43), activities of daily living (MD −0.65, 95% CI −1.77 to 0.47), or LEDD (MD −114.40 mg/day, 95% CI −258.82 to 30.02). A small but significant improvement in QoL was observed (SMD −0.26, 95% CI −0.44 to −0.07). Serious adverse events were not significantly increased (RR 1.39, 95% CI 0.56-3.49), whereas overall adverse events were more common with nicotine (RR 1.51, 95% CI 1.23-1.86), particularly gastrointestinal symptoms. Substantial heterogeneity was present for motor outcomes and LEDD. Conclusions: Current evidence does not support the routine use of nicotine as symptomatic therapy for PD. Although a modest improvement in QoL was observed, it was accompanied by a higher burden of adverse events and no significant benefit in motor outcomes. Larger, adequately powered trials are needed.</jats:p>