Effect of levetiracetam on cognitive functions and quality of life: A one-year follow-up study

Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona Spain.
Epileptic disorders: international epilepsy journal with videotape (Impact Factor: 0.95). 01/2009; 10(4):297-305. DOI: 10.1684/epd.2008.0227
Source: PubMed


The purpose of the study was to assess changes in cognitive functions and quality of life in patients with epilepsy over one year of treatment with levetiracetam (LEV) as add-on therapy.
Thirty-two patients (16 women; 16 men) who received LEV as an add-on treatment were included, and 27 completed the one-year follow-up period. Extensive neuropsychological assessments, together with a quality-of-life questionnaire were administered at baseline and at one, three, six and twelve months after beginning the add-on treatment. Patients received LEV starting with 500 mg/day in the first week, increasing by a further 500 mg/day per week until a target dose of 2 000 mg/day was reached by the end of the first month.
At the one-year follow-up, a significant improvement was observed in measurements of prospective memory, working memory, motor functions, verbal fluency, attention and quality of life. Performance for neuropsychological and quality-of-life tests was not affected by external variables such as seizure reduction or changes in previous anti-epileptic treatment. Slight changes between patients were observed, but these were not clinically significant.The limited sample size and the lack of a control group should be mentioned as limitations of the study. No control group was evaluated as in our clinical practice it was difficult to establish a comparable group of patients. Changes in the different variables were assessed by comparing baseline information with follow-up results.Despite the study limitations, we consider that the one-year treatment period provides valuable information regarding the drug's long-term effects in this setting.
Results of the present study suggest that long-term LEV treatment as add-on therapy does not interfere with cognitive function and improves quality of life.

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    • "On the other hand, LEV as a member of the pyrrolidine class of drugs, may improve cognition via enhancing higher integrative mechanisms of the brain.80,81 In fact, LEV has been shown to improve a range of cognitive abilities, including visual short-term memory,82 working memory,83 motor functions,83 psychomotor speed and concentration,72,84 and fluid intelligence.85 Comparative data are scarce – while one small comparative study showed no difference in cognitive outcomes in patients with epilepsy treated with LEV versus PHT, the authors recognized the lack of power to detect such a difference (n=10; participants taking concurrently various AEDs including PHT, CBZ, and/or VPA).86 "
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    ABSTRACT: Traumatic brain injury (TBI) leads to many undesired problems and complications, including immediate and long-term seizures/epilepsy, changes in mood, behavioral, and personality problems, cognitive and motor deficits, movement disorders, and sleep problems. Clinicians involved in the treatment of patients with acute TBI need to be aware of a number of issues, including the incidence and prevalence of early seizures and post-traumatic epilepsy (PTE), comorbidities associated with seizures and anticonvulsant therapies, and factors that can contribute to their emergence. While strong scientific evidence for early seizure prevention in TBI is available for phenytoin (PHT), other antiepileptic medications, eg, levetiracetam (LEV), are also being utilized in clinical settings. The use of PHT has its drawbacks, including cognitive side effects and effects on function recovery. Rates of recovery after TBI are expected to plateau after a certain period of time. Nevertheless, some patients continue to improve while others deteriorate without any clear contributing factors. Thus, one must ask, 'Are there any actions that can be taken to decrease the chance of post-traumatic seizures and epilepsy while minimizing potential short- and long-term effects of anticonvulsants?' While the answer is 'probably,' more evidence is needed to replace PHT with LEV on a permanent basis. Some have proposed studies to address this issue, while others look toward different options, including other anticonvulsants (eg, perampanel or other AMPA antagonists), or less established treatments (eg, ketamine). In this review, we focus on a comparison of the use of PHT versus LEV in the acute TBI setting and summarize the clinical aspects of seizure prevention in humans with appropriate, but general, references to the animal literature.
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    ABSTRACT: Antiepileptic drugs (AEDs) have been available for many years; yet, new members of this class continue to be identified and developed due to the limitations of existing drugs, which include a propensity for cognitive impairment. However, there is little preclinical information about the cognitive effects they produce, which clinically include deficits in attention and slowing of reaction time. The purpose of this study was to profile two first-generation AEDs, phenytoin and valproate, and three second-generation AEDs, levetiracetam, pregabalin and lacosamide. Initially, each drug was examined across a range of well characterised preclinical seizure tests, and then each drug was evaluated in the five-choice serial reaction time test (5-CSRTT) based on efficacious doses from the seizure tests. Each AED was tested for anti-seizure efficacy in either (1) the maximal electroshock seizure test, (2) s.c. PTZ seizure test, (3) amygdala-kindled seizures and (4) the genetic absence epilepsy rat of Strasbourg model of absence seizures. On completion of these studies, each drug was tested in rats trained to asymptotic performance in the 5-CSRTT (0.5 s SD, 5 s ITI, 100 trials). Male rats were used in all studies. Each AED was active in at least one of the seizure tests, although only valproate was active in each test. In the 5-CSRT test, all drugs with the exception of levetiracetam, significantly slowed reaction time and increased omissions. Variable effects were seen on accuracy. The effect on omissions was reversed by increasing stimulus duration from 0.5 to 5 s, supporting a drug-induced attention deficit. Levetiracetam had no negative effect on performance; indeed, reaction time was slightly increased (i.e. faster). These results highlight somewhat similar effects of phenytoin, valproate, pregabalin and lacosamide on attention and reaction time, and comparison to efficacious doses from the seizure tests support the view that there may be a better separation with the newer AEDs. Levetiracetam had no detrimental effect in the 5-CSRTT, which may be consistent with clinical experience where the drug is considered to be well tolerated amongst the AED class.
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    ABSTRACT: A previously healthy 26 years old right-handed mansustained a penetrating brain injury (PBI) from gunshotwound to the head. The bullet entered the right parietooccipitaljunction, traveled diagonally through the occipitalpole and ended in the left fronto-temporal lobe. Hedeveloped right hemiparesis and global aphasia. He wasenrolled in speech therapy (ST), and was started onlevetiracetam (LEV) 500 mg twice daily (BID) for seizureprophylaxis, then LEV was increased to 750mg BID.After 8 days on LEV 750 mg BID the patient pronouncedthe names of his children and answered questionsappropriately with verbal “yes” and “no”. At discharge,FIM scores in comprehension, expression, memory, andsocial interaction had all improved from 2 to 4. He wasable to respond verbally at the 1-3 word level with 50%accuracy and had shown improvement in auditorycomprehension and verbal expression. The patient waskept on LEV 750 mg BID for 7 months. He had 50outpatient ST sessions. At 9 months, he was able to reada paragraph he had written, and used a paper guide toscan lines. His comprehension of the written languageimproved to the sentence level, and his moneymanagement skills improved to modified independent.Conclusions: LEV appears to improve aphasia andcognitive outcomes of PBI patients treated with ST. Largeprospective randomized trials are needed to confirm thisclinical observation and to establish treatment protocolsfor PBI-induced aphasia that will incorporate ST and LEV.
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