The Role Of Antipsychotics In Treatment Of Huntington’s Disease

As until now still no available treatment can cure HD thus treatment solely based on symptomatic management of behavioural, psychiatric disturbances and motor disorder. So far there is no internationally recognized golden standard of care for HD. The only treatment approved by FDA is Tetrabenazine (TBZ) which acts as a reversible and selective depletion of monoamines such as dopamine, serotonin, norepinephrine and histamine from the nerve terminal. It is a fine-line treatment for HD (Tatiana Yero, 2008; Unti, Mazzucchi, Palermo, Bonuccelli & Ceravolo, 2016) in treatment of choreic-athetosis movements which provides great efficacy with little and tolerable adverse effect.

Unfortunately, at this point of time the drug is not available in Malaysia. Although how dopamine system give rise to psychopathology of HD still remain unclear. The emergence of involuntary movement in which responded to anti-dopamine drug gave rise to the hypothesis that there might be several DA receptors being overstimulated in the subcortical layer in individual suffered from HD. Other neurotransmitter for instance glutamate is another potential therapeutic target for treatment in HD. As the disease progress, more dopaminergic terminals become degenerated thus explain the decline of responsivity of antipsychotic to HD patient in the later stages of the disease.

A retrospective analysis on 2128 HD patients (Unti, Mazzucchi, Palermo, Bonuccelli & Ceravolo, 2016) revealed that few antipsychotics and antidepressants are commonly prescribed by clinicians in European countries in reference to their cultural influences in drug choices. Among the antipsychotics prescribed were ( 13% Tiapride, 12 % Olanzapine, 8% Risperidone, 8% TBZ, 6% Sulpiride, 6% Haloperidol), the antidepressants were (15% Citalopram, 9% Paroxetine, 8% Sertraline). Clinicians tend to choose atypical antipsychotics in treatment of HD in order to reduce risk of the adverse effect, however the study by (Unti, Mazzucchi, Palermo, Bonuccelli & Ceravolo, 2016) revealed that atypical antipsychotics are not superior than the typical antipsychotic in term of treatment efficacy. Moreover atypical antipsychotic might predisposed the individual to more metabolic adverse effect later. Therefore the choice of treatment should be in reference to the individual’s age, comorbidities, clinical phenotype and staging of disease. Adopted from Huntington's Disease Society of America. (2014).

Caregiver Guide for Mid to Late Stage Huntington’s Disease: For Long-Term Care Facilities and In-Home Care Agencies. Typical antipsychotic such as Haloperidol could be the drug of choice in the presence of significant chorea. There were few retrospective studies and small open-label studies with the used of psychometric assessment tool that measure the involuntary movement revealed the usefulness of Haloperidol to control involuntary movements without worsening of the motor performance. The improvement in abnormal movements is > 30% observed with the oral doses of Haloperidol range from 1. 5-10mg/day in an open pilot study for 10 patients.

In another study on 13 HD (single-blind) with daily dose titrated up to 80mg/day significantly reduced the severity of choreic-athetosis movement without causing ataxia and affect the gait pattern. Overstimulation of Dopamine released that acts on D2 receptor could promote the toxicity of mutant Htt on striatal neurons and Haloperidol was believed could reduce the vulnerability of striatal cells to the mutant Htt thus explained how haloperidol plays a role in treatment of HD. Fluphenazine (Caine and Shoulson,1983) reported one HD patient with auditory and tactile hallucination as well as paranoid delusion Risperidone Olanzapine.