levetiracetam and Dyskinesia--Drug-Induced

Levetiracetam, a novel antiepileptic drug, has shown antidyskinetic effects in experimental animal models of Parkinson's disease (PD). The tolerability and efficacy of levetiracetam in reducing the levodopa-induced dyskinesia (LID) in PD patients have not been established. Therefore, this study aims to synthesize evidence from published prospective clinical trials about the efficacy of levetiracetam for the management of LID in PD patients.. We followed the PRISMA statement guidelines during the preparation of this systematic review. A computer literature search of PubMed, EBSCO, Scopus, MEDLINE, and the web of science was carried out. We selected prospective clinical trials assessing the anti-dyskinetic efficacy of levetiracetam for treating LID in patients with PD. The Abnormal Involuntary Movement Scale (AIMS), Clinical Global Impression Score (GCI), UPDRS III, and UPDRS IV were considered as the primary outcome measures; their data were extracted and reviewed.. Our review included seven clinical trials with a total of 150 patients. Of them, three studies were randomized controlled trials, and the remaining were open-label single arm trials. Four studies reported poor tolerability of the levetiracetam with mild anti-dyskinetic effects. Levetiracetam slightly improved the UPDRS-IV and AIMS scores with small effect size. In the remaining three studies, levetiracetam failed to exhibit any anti-dyskinetic effects.. Current evidence does not support the efficacy of the levetiracetam for treating LID in PD patients, however, due to the limited number of published randomized control trials (RCTs), further RCTs are required.

Topics: Anticonvulsants; Antiparkinson Agents; Dyskinesia, Drug-Induced; Humans; Levetiracetam; Levodopa; Parkinson Disease; Treatment Outcome

The efficacy and safety of levetiracetam (LEV), administered for management of levodopa-induced dyskinesias (LID) in Parkinson's disease (PD), was examined using a multicenter, double-blind, placebo-controlled, parallel groups, crossover trial. Because of having a period effect, data after crossover point was excluded from analysis. Levodopa-treated PD participants with LID (n = 38) received LEV 500 mg/day, were assessed, titrated to 1,000 mg/day and reassessed, before and after crossover. The placebo group followed the same routine. Primary efficacy was defined from percent change in "On with LID" time from patient diaries. Secondary efficacy assessment used "On without LID," "Off" time, unified PD rating scale (UPDRS), clinical global impression (CGI), and Goetz dyskinesia scale after levodopa challenge. Safety measures were also performed. On with LID time decreased 37 minutes (95% confidence interval [CI] 0.59, 7.15; P = 0.02) at 500 mg/day, 7.85% 75 minutes (95% CI 3.3, 12.4; P = 0.002) at 1,000 mg/day. On without LID time increased by 46 minutes (95% CI -1.55, -0.03; P = 0.04) at 500 mg/day and 55 minutes (95% CI -10.39, -1.14; P = 0.018) at 1,000 mg/day. UPDRS 32 showed decreased dyskinesia duration mean change 0.35 (95% CI 0.09, 0.5; P = 0.009) at 1,000 mg/day. CGI showed LID decreased by 0.7 (95% CI 0.21, 1.18; P = 0.006) at 1,000 mg/day. Patient diaries and UPDRS show no increase in Off time. This exploratory trial provides evidence that LEV in 1,000 mg/day, slowly titrated, could be useful in improving LID as was assessed with patient diaries, UPDRS, and CGI scales, safely, with minimal side effects.

Topics: Adult; Aged; Aged, 80 and over; Antiparkinson Agents; Cross-Over Studies; Double-Blind Method; Dyskinesia, Drug-Induced; Female; Humans; Levetiracetam; Levodopa; Male; Middle Aged; Parkinson Disease; Piracetam; Treatment Outcome

This randomized double blind, placebo-controlled crossover study investigated the antidyskinetic effects of levetiracetam in Parkinson's disease.. Sixteen participants with levodopa-induced dyskinesia were enrolled. Hourly videotaped dyskinesia assessments scored by the Goetz method and hourly Unified Parkinson's Disease Rating Scale motor subscale scoring were conducted on 1 day at the end of each treatment period.. Dyskinesia was slightly less on placebo (P = .26). Patient diary records also showed less dyskinesia on placebo (P = .10). Parkinsonism was a little worse on levetiracetam, at borderline statistical significance (P = .05).. Levetiracetam was well tolerated at doses up to 2000 mg per day, but we did not detect any antidyskinetic properties.

Topics: Anticonvulsants; Antiparkinson Agents; Cross-Over Studies; Double-Blind Method; Dyskinesia, Drug-Induced; Humans; Levetiracetam; Levodopa; Parkinson Disease; Piracetam; Severity of Illness Index; Time Factors; Video Recording

The goal of this study was to evaluate the efficacy and safety of levetiracetam versus placebo for tardive dyskinesia (TD).. This double-blind, placebo-controlled, randomized study was conducted at the Connecticut Mental Health Center between September 2004 and April 2006. Antipsychotic-treated patients meeting Glazer-Morgenstern criteria for TD were assigned at random to receive levetiracetam 500 mg/day to 3000 mg/day or placebo for 12 weeks. After completion of 12 weeks, patients were permitted to receive open-label levetiracetam for a further 12 weeks. The principal efficacy outcome measure was improvement in the Abnormal Involuntary Movement Scale (AIMS) total score. Safety was assessed with an adverse event scale, psychiatric symptom rating scales, weight, and hematologic tests.. A total of 50 patients were randomly assigned to treatment. AIMS total scores were moderate in severity at baseline. Mixed regression models revealed that AIMS total scores declined 43.5% from baseline in the levetiracetam group compared to 18.7% for placebo (p = .022). Patients continuing levetiracetam in the open-label phase continued to improve, and patients crossed over to open-label levetiracetam improved to a similar degree as those initially assigned. Levetiracetam was well tolerated.. Levetiracetam appeared effective for TD in this study. The mechanisms of its therapeutic effect are unclear but may involve reducing neuronal hypersynchrony in basal ganglia. Future studies should attempt to replicate the current results.. clinicaltrials.gov Identifier: NCT00291213.

Topics: Algorithms; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Administration Schedule; Dyskinesia, Drug-Induced; Female; Humans; Levetiracetam; Male; Middle Aged; Nootropic Agents; Piracetam; Treatment Outcome

Topics: Adult; Aged; Anticonvulsants; Antipsychotic Agents; Dyskinesia, Drug-Induced; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome

Dyskinesia is a movement disorder categorized by involuntary movement of muscle. Although dyskinesia can be brought on by taking medications, it can also be a symptom of a variety of diseases. Antiepileptic drug-induced involuntary movements have been well researched. Rare reports have been made for dyskinesia, a type of dystonia caused by phenytoin. The mechanism of its occurrence must be succinctly studied.. A 53-year-old Asian patient taking phenytoin (100 mg twice daily) experienced symptoms of perioral muscle involuntary movement, impaired speech, and generalized tremors and was admitted to the hospital. Brain magnetic resonance imaging showed significant development of encephalomalacia and porencephaly. The serum phenytoin levels were in the toxic range (33 g/ml). These were suggestive of phenytoin-induced dyskinesia. Levetiracetam and clonazepam were initiated, and the patient showed significant improvement in the symptoms.. This case presented a substantial reference value for the differential diagnosis and treatment prognosis of phenytoin-induced dyskinesia. The phenytoin-induced dyskinesia in this patient was successfully reversed with prompt identification and treatment. According to the case study's findings, such people may benefit from periodic therapeutic drug monitoring.

Topics: Anticonvulsants; Dyskinesia, Drug-Induced; Dystonia; Humans; Levetiracetam; Middle Aged; Phenytoin

Topics: Antipsychotic Agents; Dyskinesia, Drug-Induced; Female; Follow-Up Studies; Humans; Levetiracetam; Middle Aged; Piracetam; Psychotic Disorders; Time Factors; Treatment Outcome

To describe successful treatment of tardive dyskinesia with levetiracetam.. Tardive dyskinesia is a late-onset movement disorder caused by exposure to dopamine receptor blocking agents, most commonly neuroleptics. Metoclopramide is frequently used to treat gastrointestinal dysmotility. It has antidopaminergic properties, and is estimated to be responsible for two-thirds of drug-related movement disorders.. Case report.. A 68-year-old woman presented with a history of intestinal transplantation (12 years ago; short gut syndrome related to bowel resection for rectal carcinoma) and renal transplantation (1 year ago; diabetes). She developed involuntary movements with stereotypic oro-buccal-lingual dyskinesias and right-sided choreiform movements. Her Abnormal Involuntary Movement Scale score (AIMS) score was 27. She has been treated with metoclopramide for gastrointestinal dysmotility for more than 10 years and was diagnosed with tardive dyskinesia. Treatment with levetiracetam 250 mg orally b.i.d. led to a significant improvement of abnormal movements within a week. Her AIMS score decreased to 8.. Tardive dyskinesia may be quite disabling and options include withdrawal of offending medication, or use of tetrabenazine or reserpine. Several reports also suggested improvement of tardive movement disorders with levetiracetam. In our patient, levetiracetam relieved symptoms of tardive dyskinesia and allowed continuous use of metoclopramide. Larger studies are needed to confirm its efficacy.

Topics: Aged; Anticonvulsants; Antiemetics; Dyskinesia, Drug-Induced; Female; Humans; Levetiracetam; Metoclopramide; Piracetam

Topics: Aged; Anticonvulsants; Antiparkinson Agents; Dyskinesia, Drug-Induced; Female; Humans; Levetiracetam; Levodopa; Male; Middle Aged; Parkinson Disease; Piracetam

We evaluated the tolerability and preliminary efficacy of levetiracetam (LEV; Keppra) in reducing levodopa-induced dyskinesias in Parkinson's disease (PD) in an open-label pilot study. Nine PD patients who were experiencing peak-dose dyskinesias for at least 25% of the awake day and were at least moderately disabling were treated with LEV in doses up to 3,000 mg for up to 60 days. The primary outcome measure was the percent of the awake day that patients spent on without dyskinesia or with nontroublesome dyskinesia (good on time). The mean dose of LEV at endpoint was 625+/-277 mg/day. LEV significantly improved percent of the awake day on without dyskinesia or with nontroublesome dyskinesia at endpoint compared to baseline (43% +/- 12% vs. 61% +/- 17%; P=0.02). Percent on time with troublesome dyskinesia decreased from 23% +/- 10% at baseline to 11% +/- 6% at endpoint, although not significantly. There was no significant increase in off time from baseline to endpoint. There was a 56% dropout rate, mostly due to somnolence. In PD patients who experienced peak-dose dyskinesia for at least 25% of the awake day, LEV significantly improved on time without dyskinesia or with nontroublesome dyskinesia.

Topics: Aged; Anticonvulsants; Antiparkinson Agents; Dyskinesia, Drug-Induced; Female; Humans; Levetiracetam; Levodopa; Male; Middle Aged; Parkinson Disease; Pilot Projects; Piracetam

L-3,4 dihydroxyphenylalanine (levodopa)-induced dyskinesia in Parkinson's disease patients is characterized by a mixture of chorea and dystonia. Electrophysiological studies suggest that chorea is associated with abnormal synchronization of firing of basal ganglia neurons while dystonia is not. Levetiracetam is a novel anti-epileptic drug known to exhibit unique desynchronizing properties in contrast to other anti-epileptic drugs. We assessed the anti-dyskinetic efficacy of levetiracetam (13, 30 and 60 mg/kg, p.o.) administered in combination with an individually tailored dose of levodopa (Levodopa/carbidopa, 4:1 ratio, 19+/-1.8 mg/kg, p.o.), in six dyskinetic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaques. Levetiracetam (60 mg/kg) significantly reduced levodopa-induced chorea during the first hour post-treatment but had no effect on dystonia. Levetiracetam, at all doses tested, had no effect on the anti-parkinsonian action of levodopa. These results suggest that levetiracetam may provide a novel therapeutic approach specifically aimed at the choreic form of levodopa-induced dyskinesia.

Topics: Animals; Chorea; Dose-Response Relationship, Drug; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Levetiracetam; Levodopa; Macaca fascicularis; MPTP Poisoning; Piracetam

Topics: Adrenergic alpha-Agonists; Anticonvulsants; Antidepressive Agents; Chronic Disease; Clonidine; Depression; Dyskinesia, Drug-Induced; Female; Humans; Hypotension; Levetiracetam; Lithium Carbonate; Middle Aged; Piracetam