Short‐term continuous infusion of apomorphine hydrochloride for treatment of Huntington's chorea: A double blind, randomized cross‐over trial

Abstract

We evaluated tolerability and the efficacy of continuous infusion of apomorphine hydrochloride on involuntary movements and mood disorder in Huntington's disease (HD) patients in a pilot, single center, double-blind, randomized, crossover, and controlled versus placebo study. Nine patients with a molecular diagnosis of HD were screened for response to acute apomorphine injection. Four of them, not ameliorating at the acute test, were discontinued. Five patients, responding to acute apomorphine, received continuous infusion of either apomorphine or placebo for 5 days. After 2 days of washout, the alternative treatment was administered. Primary endpoint measures were scores of the Unified Huntington's Disease Rating Scale (UHDRS "motor section") and of the Abnormal Involuntary Movement Scale (AIMS). Secondary endpoint measures were the Hamilton Depression Rating Scale (HAD) score and safety parameters. Both UHDRS and AIMS scores significantly decreased in all patients after apomorphine. The beneficial effect of apomorphine was recorded throughout the 5 treatment days. The HAD score did not change after infusion of either treatment. No serious adverse events were reported by either group during the study. Our results suggest that continuous infusion of apomorphine might be considered for the treatment of involuntary movements in some HD patients.

Rating scales for behavioral symptoms in Huntington's disease: Critique and recommendations

“…It was originally developed for hospital inpatients suffering from affective disorder, which explains the emphasis on melancholic and physical symptoms of depression. The HAM‐D has been used in many studies in HD to assess depressive symptoms, including clinical trials . It has been shown to correlate with the “depressed mood” item of the UHDRS ( r = 0.917) .…”

Treatment of Huntington's Disease

“…At this dose, sedation becomes a potential adverse effect. In a few short-term studies (hours), there is evidence that dopamine agonists may reduce the motor signs of HD, vaguely defined as "abnormal involuntary movements" in 2 of the studies and a reduction in the UHDRS total motor score and abnormal involuntary movement scale (AIMS) with apomorphine infusion [100][101][102]. Although the pharmacological rationale for using dopamine agonists in the treatment of chorea is not clear, presumably they act by activating the presynaptic dopamine receptors leading to decreased dopamine turnover.…”

Rating Scales for Motor Symptoms and Signs in Huntington's Disease: Critique and Recommendations

“…No clinimetric data on reliability or validity of the AIMS are available in HD. The AIMS has been used in several clinical trials targeting the treatment of chorea in HD and has been shown to be sensitive to change after treatment …”