Potential for Intrathecal Baclofen in Treatment of Essential Tremor

Abstract

Introduction: Essential tremor (ET) is the most common movement disorder of adults, affecting an estimated 7 million Americans. Symptoms of ET range from slightly noticeable to debilitating, with 1 cohort study finding 15% of patients were forced into early retirement. Additionally, depression has also been correlated with the severity of disability of ET. Treatment options include propranolol and primidone. Current treatment options are not very effective, with more than half (56.3%) of patients discontinuing medications because of no changes in symptoms.

Methods: Unfortunately, there is a relative void and controversy in the literature explaining ET pathophysiology; however, the gamma-aminobutyric acid (GABA) hypothesis is the strongest. We conducted a PubMed search on 30 September 2015 with no time constraints using the search terms "essential tremor" and "baclofen," which resulted in a total of 5 articles.

Results: Neurohistopathologic studies have demonstrated decreased GABA-A and GABA-B receptors in the cerebellar cortex of ET patients. GABA, the major inhibitory neurotransmitter in the central nervous system, is proposed to have an inhibitory effect on pacemaker output activity of the cerebello-thalamo-cortical pathway, with lower receptors resulting in decreased inhibition of baseline tremors. Tariq et al showed delayed onset and intensity of tremor with oral administration of R-baclofen in a mouse model of ET.

Conclusion: With a better side-effect profile and success in a physiologically related condition, we propose more clinical trials and research be carried out on intrathecal baclofen as a potential treatment option, especially drug refractory ET, so as to increase the quality of life of this patient population.

Keywords: Baclofen; Essential tremor; Intrathecal baclofen; Literature review; Primidone; Propranolol.