Deutetrabenazine was developed in an effort to create an effective, longer-acting, safer medication for reducing chorea.įirst-HD is a completed phase III randomized, double-blind, placebo-controlled trial of deutetrabenazine in 90 HD patients with chorea. This reduces the impact of CYP2D6 variants on drug metabolism, and can potentially reduce limiting peak dose side-effects while maintaining efficacy level. The deuterium atoms at key positions in the molecule prolong plasma half-life and reduce metabolic variability relative to the nondeuterated metabolites from TBZ ( Sampaio et al., 2014). Testa, in Handbook of Clinical Neurology, 2017 Deutetrabenazineĭeutetrabenazine is a novel molecule that contains six deuterium atoms instead of six hydrogen atoms in specific positions in the TBZ molecule and retains the intrinsic pharmacologic activity of TBZ. Recent trials 1 involving intrathecal administration of IONIS-HTT Rx, an antisense oligonucleotide designed to inhibit HTT messenger RNA and thereby reduce concentration of mutant huntingtin in patients with early Huntington disease, have shown dose-dependent reductions in concentration of mutant huntingtin without serious side effects.Īnindita Deb.
ĭepression with suicidal ideation is common may improve with tricyclic antidepressants or SSRIs.Īmantadine (up to 300 to 400 mg divided tid).Neuroleptics, typical or atypical, can be used for symptomatic management of neuropsychiatric issues and chorea at low doses (e.g., haloperidol 1 to 10 mg/day). Both drugs are expensive and have no effect on disease progression. Deutetrabenazine appears to have a lower incidence of neuropsychiatric adverse effects than tetrabenazine. Side effects include parkinsonism and severe depression. They are both a reversible inhibitor of the vesicle monoamine transporter type 2 (VMAT-2), inhibiting primarily dopamine and to a lesser degree serotonin and norepinephrine. Tetrabenazine and deutetrabenazine are both approved by the FDA for the symptomatic treatment of chorea seen in Huntington disease. Chorea does not need to be treated unless it is disabling.
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