Current therapeutic options for Huntington's disease: Good clinical practice versus evidence‐based approaches?

Abstract

Therapeutic decision-making in Huntington's disease (HD) is often guided by clinical experience, because of the limited empirical evidence available. The only medication for HD that has met the regulatory hurdle for approval is tetrabenazine, indicated for the treatment of chorea. However, its use has limitations, and in the setting of specific contraindications or comorbidities the treatment of choice for chorea is still the multipurpose antipsychotics. For the management of psychiatric disturbances, selective serotonin reuptake inhibitors (SSRIs) and mood stabilizers are often used, although empirical evidence is lacking. Finally, no known effective treatment is available for cognitive dysfunction in HD. We discuss the limited evidence available and current expert opinion on medical treatment of the dominant motor, psychiatric, and cognitive features of HD. This follows a brief introduction on the general principles of HD management and on evidence-based medicine in relation to clinical practice.

Compromised Dopaminergic Encoding of Reward Accompanying Suppressed Willingness to Overcome High Effort Costs Is a Prominent Prodromal Characteristic of the Q175 Mouse Model of Huntington's Disease

“…4A). We therefore further assessed how dopamine encodes behavior during the final eight completed trials of each animal's PR session (Wanat et al, 2010). As mice reached their individual breakpoint, reward-evoked dopamine release differed between Q175 and WT mice and across trials (Fig.…”

“…These nonmotor symptoms severely impact daily functioning and quality of life for HD patients and caregivers (Hamilton et al, 2003;Papoutsi et al, 2014), but are poorly understood and insufReceived Jan. 13, 2016; revised March 10, 2016; accepted March 15, 2016. Author contributions: D.P.C.…”

“…Psychiatric deficits in Huntington's disease (HD) appear early during a prodromal stage that precedes motor deficits (eg, chorea) by a decade or more (Paulsen et al, 2008;Epping et al, 2016). These nonmotor symptoms severely impact daily functioning and quality of life for HD patients and caregivers (Hamilton et al, 2003;Papoutsi et al, 2014), but are poorly understood and insuf-ficiently treated (Frank, 2014).…”

“…These nonmotor symptoms severely impact daily functioning and quality of life for HD patients and caregivers (Hamilton et al, 2003;Papoutsi et al, 2014), but are poorly understood and insuf-ficiently treated (Frank, 2014). Whereas striatal medium spiny neuron (MSN) degeneration represents the canonical, histopathological hallmark of HD (Reiner et al, 1988;Vonsattel and DiFiglia, 1998), altered dopamine input onto striatal MSNs is also implicated (Klawans et al, 1970;Spokes, 1980) and may promote early psychiatric impairments .…”

“…Whereas striatal medium spiny neuron (MSN) degeneration represents the canonical, histopathological hallmark of HD (Reiner et al, 1988; Vonsattel and DiFiglia, 1998), altered dopamine input onto striatal MSNs is also implicated (Klawans et al, 1970; Spokes, 1980) and may promote early psychiatric impairments . However, the functional nature of dopaminergic deficits and their behavioral relevance in HD remains controversial as estimates of extracellular dopamine levels in HD patients and animal models have been inconsistent (Cepeda et al, 2014;Schwab et al, 2015). Addressing this question is particularly important because the only FDA-approved pharmaceutical treatment option for HD targets chorea and is confined to agents that inhibit the vesicular monoamine transporter-2 (VMAT-2) to disrupt extracellular dopamine release (Venuto et al, 2012).…”