Hyperdopaminergic crises in familial dysautonomia: a randomized trial of carbidopa

Abstract

Objective: The purpose of this study was to determine whether carbidopa (Lodosyn), an inhibitor of dopa-decarboxylase that blocks the synthesis of dopamine outside the brain, is an effective antiemetic in patients with familial dysautonomia (FD) and hyperdopaminergic nausea/retching/vomiting attacks.

Methods: We enrolled 12 patients with FD in an open-label titration and treatment study to assess the safety of carbidopa. We then conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate its antiemetic efficacy.

Results: Previous fundoplication surgery in each patient studied prevented vomiting, but all of the subjects experienced severe cyclical nausea and uncontrollable retching that was refractory to standard treatments. Carbidopa at an average daily dose of 480 mg (range 325-600 mg/day) was well tolerated. In the double-blind phase, patients experienced significantly less nausea and retching while on carbidopa than on placebo (p < 0.03 and p < 0.02, respectively). Twenty-four-hour urinary dopamine excretion was significantly lower while on carbidopa (147 ± 32 µg/gCr) than while on placebo (222 ± 41µg/gCr, p < 0.05).

Conclusions: Carbidopa is a safe and effective antiemetic in patients with FD, likely by reducing the formation of dopamine outside the brain.

Classification of evidence: This study provides Class II evidence that carbidopa is effective in reducing nausea/retching/vomiting in patients with FD.

Figures

Figure 1. Open-label phase

(A) Bar chart shows mean (unadjusted) composite nausea scores at baseline and during the open-label treatment phase. (B) Line graph shows 24-hour dopamine (DA) excretion at baseline and on carbidopa (open-label). (C) Scatterplot shows the significant relationship between nausea scores and dopamine excretion during the open-label phase (y = 0.0199x + 6.9212, R² = 0.19134).

Figure 2. Double-blind phase

Bar charts show change in symptom scores from baseline during the randomized, double-blind, placebo-controlled phase. Greater reduction in scores indicated symptomatic improvement (2-way analysis of variance). *p < 0.01, **p < 0.05, ***p < 0.02.