Effect of Amantadine in Essential Tremor: A Randomized, Placebo-Controlled Trial Alexandre Gironell, MD, Jaime Kulisevsky, MD, * Berta Pascual-Sedano, MD, and David Flamarich, PhD Movement Disorders Unit, Department of Neurology, Sant Pau Hospital, Autonomous University of Barcelona, Catalonia, Spain Abstract: There is a need for new medication for essential tremor (ET). Preliminary evidence suggests that amantadine may be effective in the treatment of ET. We studied the effects of amantadine in a double-blind, cross-over, placebo-controlled trial in ET patients. Sixteen patients with ET received amanta- dine 100 mg b.i.d. and placebo for 15 days, with a 1-week wash-out period between treatments. Major evaluation out- comes consisted of a tremor clinical rating scale, acceleromet- ric recordings, and a self-reported disability scale obtained before drug intake and on study days 1 and 15 of each treatment period. A two-way repeated measures analysis of variance (treatment, time) was applied. Any P value  0.05 was con- sidered significant. On day 15, amantadine did not demonstrate any significant efficacy in reducing tremor with respect to baseline in any tremor measures. An increase in postural tremor as an adverse effect of amantadine was referred by 37.5% of patients. Results from the present trial indicate amantadine at 100 mg b.i.d. is not effective as a treatment for ET. © 2005 Movement Disorder Society Key words: amantadine; essential tremor; accelerometry Essential tremor (ET) is one of the most common movement disorders and is characterized by tremor dur- ing the maintenance of posture and active movement. 1,2 Drug treatment for ET remains poor and often unsatisfac- tory. 3 The efficacy of primidone and beta-adrenergic antag- onists, such as propranolol, has been demonstrated, 4–6 but many patients, particularly the elderly, do not benefit from these drugs because of contraindications, adverse reactions, and failure to achieve adequate tremor control. Amantadine, originally used in the treatment and pro- phylaxis of influenza, has also proved beneficial in neu- rological conditions, including drug-induced Parkinson- ism, Parkinson’s disease, traumatic head injury, dementia, multiple sclerosis, and cocaine withdrawal. 7–14 The pos- sible efficacy of amantadine in ET is based on four uncontrolled studies, the latest conducted in 1986. 15–18 No controlled studies exploring this hypothesis have been published to date. We explored the effects of aman- tadine in ET with a double-blind, cross-over, placebo- controlled design using both subjective (clinical scales) and objective (accelerometric recordings) measures. PATIENTS AND METHODS Included in the study were 16 patients (7 male, 9 female; mean age, 71.4 years; range, 60 to 79 years; mean tremor duration, 12.2 years; range, 4 to 26 years) diagnosed of ET at the Sant Pau Neurology Department Movement Disorders Unit and suffering moderate (suf- ficient to cause mechanical or social disability) to severe ET, according to a previous sample size calculation. Diagnosis of ET was established using consensus criteria on the basis of chronic (i.e., longer than 5 years), per- sistent (although the amplitude may fluctuate), bilateral (although it may be asymmetrical) postural tremor with or without kinetic tremor involving hands or forearms (although tremor of other body parts may be present in addition to upper limb tremor), with no other neurolog- ical abnormalities related to systemic or other neurolog- ical disease (with the exception of the presence of tremor, cogwheeling, and Froment’s sign) and no other explanation for tremor (e.g., the presence of known causes of enhanced physiological tremor, concurrent or recent exposure to drugs known to cause tremor, or the presence of drug withdrawal state). 19 Moreover, all the *Correspondence to: Dr. Jaime Kulisevsky, Movement Disorders Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Av. S.A.Ma Claret 167, 08025 Barcelona, Catalonia, Spain. E-mail: jkulisevsky@santpau.es Received 24 February 2005; Revised 11 April 2005; Accepted 17 April 2005 Published online 14 October 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20676 Movement Disorders Vol. 21, No. 4, 2006, pp. 441– 445 © 2005 Movement Disorder Society 441