Levodopa‐induced orthostatic hypotension in parkinsonism: A red flag of autonomic failure

Background and purpose: Levodopa (LD) is the main treatment for parkinsonism, but its use may be limited by a potential hypotensive effect.Methods: We evaluated the cardiovascular effect of LD performing head-up tilt test (HUTT) before and 60 min after 100/25 mg LD/dopa-decarboxylase inhibitor (pre-LD vs. post-LD HUTT) in 164 patients with parkinsonism on chronic LD treatment. Features predictive of LD-induced orthostatic hypotension (OH) were assessed by logistic regression analysis.Results: Basal supine blood pressure (BP) and heart rate (HR) decreased after LD. During post-LD HUTT, BP drop and HR increase were significantly greater than at pre-LD HUTT. Thirty-eight percent of patients had OH at post-LD HUTT compared to 22% of patients presenting OH at pre-LD HUTT (p < 0.001). Risk factors for LD-induced/worsened OH were pre-LD OH (odds ratio [OR] = 36, 95% confidence interval [CI] = 10-131), absence of overshoot at Valsalva maneuver (OR = 9, 95% CI = 4-20), and pathological Valsalva ratio (OR = 6, 95% CI = 2-15).Conclusions: LD administration caused/worsened hypotension in both supine and orthostatic conditions. Patients with cardiovascular autonomic failure had a higher risk of developing LD-induced OH. In clinical practice, LD-induced OH could represent a red flag for cardiovascular autonomic failure.