Efficacy of the long chain alcohol metabolite octanoic acid as an adjunct to standard first line therapy of classical essential tremor

Abstract

Essential tremor (ET) is a common movement disorder resulting in a postural and kinetic tremor that predominantly affects the upper extremities and varies in amplitude across patients. The etiology of ET is unclear; however, three predominant hypotheses exist. The first hypothesis evaluates rhythmical dysfunction originating from the inferior olivary nucleus that is then propagated throughout the brain and ultimately manifests as tremor. The second hypothesis evaluates γ-aminobutyric acid dysfunction as a causal explanation for ET while the third hypothesis evaluates gross cortical and cerebellar changes that result in ET.

The beta-adrenergic blocking medication propranolol and barbiturate primidone are staples for the treatment of this disorder, but often fail to adequately control symptoms. primidone specifically has intolerable side effects for many patients. Ethanol, however, can more effectively treat tremor via a mechanism likely explained by one or more of the aforementioned hypotheses. However, it is not a practical therapeutic option for the treatment of ET primarily as a result of its intoxicating properties among other reasons. Recent attention to the long chain alcohol 1-octanol and its primary metabolite octanoic acid yielded findings of tremorlytic properties, albeit at doses that limit practicality.

This study looks to evaluate octanoic acid as an adjunct to primidone and propranolol for the first time and will attempt to demonstrate that as an adjunct, it can be used at lower, more practical doses.