Treatment of essential tremor: a systematic review of evidence and recommendations from the Italian Movement Disorders Association

Abstract

Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. It often causes embarrassment and more rarely serious disability, requiring treatment. To assess the current state of knowledge on ET therapy and produce recommendations based on the analysis of evidence the authors reviewed the literature regarding pharmacologic and surgical therapies, providing a quality assessment of the studies and the strength of recommendations for each treatment. A committee of experts selected clinical-based questions to guide the search. A systematic literature review was performed to identify all the studies conducted on patients with ET published until September 2010. Articles were classified according to GRADE evidence profile, a system for grading the quality of evidence and the strength of recommendation based on the quality of the studies. The quality of evidence was often rated as "low" or "very low" for the studies analyzed. Propranolol, long-acting propranolol, primidone, and topiramate are recommended as first-line therapy, with restrictions for their side effects. Arotinolol, sotalol, ICI 118.551 and LI 32.468 (experimental drugs), zonisamide, gabapentin, alprazolam, clozapine, and olanzapine are recommended as a second-line treatment. Botulinum toxin type A and thalamic deep-brain stimulation are recommended for refractory ET. The results highlight the need of well-designed direct comparison trials aimed at evaluating relative effectiveness and safety of the drugs currently used in clinical practice. Furthermore, additional controlled clinical trials are required to define other possible treatment strategies for ameliorating the management of ET.

Apomorphine enhances harmaline-induced tremor in rats

“…Previously, Costall et al [18] reported similar effects of dopamine agonists with respect to the tremor induced by harmine (a harmaline metabolite). However, these latter results cast doubt on the usefulness of b-carboline models to screen drugs for ET, due to the lack of any data clearly showing the clinical effectiveness of dopamine agonists [1]. In contrast, the therapeutic effect of atypical neuroleptics in ET is well established [1].…”

“…However, these latter results cast doubt on the usefulness of b-carboline models to screen drugs for ET, due to the lack of any data clearly showing the clinical effectiveness of dopamine agonists [1]. In contrast, the therapeutic effect of atypical neuroleptics in ET is well established [1].…”

“…ET etiology is often genetic but environmental toxins have been proposed as risk factors. Neuronal mechanisms underlying ET are poorly understood and at present the medication for treatment of ET is unsatisfactory [1].…”

Genetics of essential tremor

“…Furthermore, processes which are under cerebellar controls are abnormal in ET patients such as the presence of intention tremors and oculomotor impairment [9]. The involvement of the cerebellum are also reflected by the high efficiency of deep brain stimulation [9] and gabapentin [10] in reducing tremor, which target the cerebellar outflow and the GABA pathways, respectively.…”

Recent Advances in Essential Tremor

“…Nearly half of the patients either cannot tolerate medications or have refractory, disabling tremor despite medication [31]. Unfortunately there has been no breakthrough development in medical treatment of ET since 4 years, only a few offlabel medications, such as beta blockers or antiepileptics are available for ET.…”