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Objective To determine whether adding orally disintegrating selegiline (ODS) while decreasing dopamine agonist (DA) dosages would reduce DA-related adverse effects (AEs) of excessive daytime sleepiness (EDS), pedal edema, hallucinations, and impulse control disorders (ICDs) without compromising efficacy in Parkinson disease (PD) patients. Methods This was a 12-week open-label study of 60 PD patients with motor fluctuations and DA-related AEs of EDS, pedal edema, hallucinations, and ICDs. Orally disintegrating selegiline was initiated at 1.25 mg once daily, and down titration of the DA was started with a goal of a 50% reduction by 1 week. At week 6, ODS was increased to 2.5 mg, and further reductions of the DA were allowed if the AEs were not resolved. Results The addition of ODS allowed a reduction in the mean daily dose of pramipexole from 2.3 to 0.5 mg and immediate-release ropinirole from 11.2 to 2.9 mg. Most subjects reported a reduction or resolution of DA-related AEs; 94% with EDS (n = 50), 73% with pedal edema (n = 26), 86% with hallucinations (n = 15), and 84% with ICDs (n = 25). Mean activities of daily living and motor scores from the Unified Parkinson's Disease Rating Scale as well as quality-of-life scores were significantly improved without an increase in daily "off" time. The most common AEs, most of which resolved after titration, were worsening of PD, nausea/vomiting, dyskinesia, increased off time, body aches, insomnia, orthostatic hypotension, and increased anxiety and depression. Conclusions In most subjects, the addition of ODS with decreasing dosages of DAs substantially reduced EDS, pedal edema, hallucinations, and ICDs without compromising efficacy.

Objective: To determine if levetiracetam is efficacious in the treatment of essential tremor. Methods: Fifteen patients (3 women), aged 35 to 83 years, with essential tremor were studied in a double-blind, placebo-controlled crossover trial of levetiracetam. During the 2 treatment periods, levetiracetam or placebo was titrated from 500 to 3000 mg/d during a 5-week titration phase, as tolerated, and the maximum tolerated dosage was then maintained for 4 weeks. There was a 3-week washout phase between the 2 treatment periods. Patients were assessed with the Fahn-Tolosa-Marin tremor rating scale (TRS), and tremor in the spiral and line drawings of 7 patients was quantified with a computerized digitizing tablet. Changes in other antitremor medications (10 patients) were not permitted during the study. Results: The planned enrollment of 45 patients was stopped when an interim analysis of the first 15 patients revealed no efficacy. One patient failed to achieve the 3000-mg/d dosage of levetiracetam. Three patients dropped out of the study due to lack of efficacy and other side effects. The analysis of TRS data with these three patients excluded and after imputing their missing data (last value carried forward) revealed a statistically insignificant trend for all TRS and tablet measures to be worse when patients were taking levetiracetam. There was no period effect or treatment-period interaction for any measure of tremor. The results were the same for the 5 patients taking no other antitremor medications. Conclusions: Levetiracetam is not beneficial in the treatment of essential tremor.

Objectives: This open-label study was performed to evaluate the efficacy and tolerability of levetiracetam for levodopa-induced dyskinesia and its effect on motor functioning and quality of life in Parkinson disease (PD) patients. Methods: PD patients with moderate to severe dyskinesia were enrolled in the study. PD medications were unchanged during the study, and levetiracetam was slowly titrated up to a maximum dosage of 3000 mg/d over a 2-month period. Results: There were 9 patients with a mean age of 65 years and mean disease duration of 13 years. Forty-four percent of the subjects withdrew before the end of the study due to adverse events, primarily worsening of PD symptoms and sleepiness. Of the remaining 5 subjects, 1 subject continued levetiracetam after the study with mild improvement in dyskinesia and 4 discontinued levetiracetam due to worsening of PD symptoms and sleepiness. Conclusions: Levetiracetam is not well tolerated in PD patients with levodopa-induced dyskinesia resulting in worsening of PD symptoms, intolerable somnolence, and worsening of dyskinesia in most patients.

Objectives This study was performed to determine if conversion from sustained release carbidopa/levodopa (SR-CL) with or without entacapone to carbidopa/levodopa/entacapone (CLE; Stalevo) improves motor functioning and quality of life in Parkinson disease (PD) patients and to assess patient tolerance and drug preference. Methods PD patients reporting suboptimal symptom control with SR-CL were converted to CLE. The basic conversion was 1 SR-CL 25/100 to 1 25/100/200 CLE and 1 SR-CL 50/200 to 1 37.5/150/200 CLE with additional changes as necessary. Results There were 62 patients with an average age of 68 years and an average disease duration of 11 years. CLE was preferred by 42 patients and SR-CL was preferred by 20 patients. In those that preferred CLE, Unified Parkinson Disease Rating Scale (UPDRS) mentation and motor subscores, Parkinson Disease Questionnaire-39 (PDQ-39) quality-of-life activities of daily living (ADL) and bodily discomfort subscores, and Epworth Sleepiness Scale (ESS) scores were significantly improved. There were no significant changes in any measures in the group that preferred SR-CL. Common adverse effects in the group that preferred CLE included nausea, vomiting, increased dyskinesia or off time, dizziness, and somnolence. The most common adverse events in the group preferring SR-CL were increased off time or dyskinesia, nausea, and vomiting. Conclusions A majority of patients suboptimally controlled on SR-CL can be successfully converted to CLE with improvements in motor function, quality of life, and sleepiness. Older patients, with longer disease duration not previously exposed to entacapone, may better tolerate CLE after the addition of entacapone.

We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.