levetiracetam and Fatigue

Many clinical interventions are trialled to manage medical complications following Traumatic Brain Injury (TBI). However, published evidence for the effects of those clinical interventions is limited. This article is an overview of common complications and their management from published systematic reviews in TBI.. A health science electronic database search for published systematic reviews for management of common complications in TBI was conducted in the last decade till 31st January 2021. Methodological quality and evidence were critically appraised using the Grading of Recommendations, Assessment, Development and Evaluations and Revised-Assessment of Multiple Systematic review tools. Overall, only six systematic reviews complied with search criteria, these evaluated fatigue, spasticity and post traumatic seizures (29 RCTs, 13 cohort studies, n = 5639 participants). No systematic reviews for other common TBI-related complications met criteria for this review. The included reviews varied from 'moderate to high' in methodological quality. The findings suggest beneficial treatment effect of anti-epileptic drugs (phenytoin/levetiracetam) compared with placebo in reducing early seizure incidence, but no significant benefit of phenytoin over levetiracetam, valproate, or neuroprotective agent for early or late posttraumatic seizures. There was 'limited' evidence for spasticity-related interventions, and 'insufficient' evidence of cardiorespiratory training on fatigue levels.. Despite the high prevalence and associated functional impact of TBI-related complications, there is limited evidence to guide treating clinicians for management of common TBI complications. More robust studies are needed to build evidence in this population.

Topics: Brain Injuries, Traumatic; Fatigue; Humans; Levetiracetam; Phenytoin; Seizures; Systematic Reviews as Topic

Cognitive impairment and seizures are common in our aging population. Anticonvulsant treatment is problematic due to sedation, cognitive slowing, and behavioral changes. Levetiracetam has favorable pharmacokinetics, good efficacy in elderly individuals, a favorable side effect profile, and lacks major drug interactions. We conducted a prospective, uncontrolled, phase 4, open label, 12-week study of levetiracetam to better profile its efficacy, safety, and impact on cognitive/behavioral status in 24 cognitively impaired, elderly individuals. In total, 69% were seizure free for the duration of the study; the remaining participants had satisfactory seizure control. Fatigue was the most common side effect (5 participants). Significant overall improvements were observed for the Folstein's Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive. No significant changes were seen in behavioral or functional measures. Levetiracetam is an effective antiepileptic drug in elderly individuals with cognitive impairment. At 3 months, participants who remained on levetiracetam showed excellent cognitive tolerability.

Topics: Aged; Aged, 80 and over; Aging; Anticonvulsants; Cognition; Cognition Disorders; Disease-Free Survival; Fatigue; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Psychiatric Status Rating Scales; Seizures; Severity of Illness Index; Treatment Outcome

The objectives of this pilot trial were to assess the potential efficacy and safety of levetiracetam for the treatment of hot flashes, a major cause of morbidity among breast cancer survivors.. Women, aged 18 years or more, with a history of breast cancer or those who wished to avoid estrogen because of a perceived increased risk of breast cancer, who were experiencing bothersome hot flashes (more than or equal to 14 times per week, for more than or equal to 1 month before study entry), were included. During the baseline week, general demographic characteristics, hot flash information, and quality of life data were obtained. At the beginning of week 2, patients were started on levetiracetam for a total of 4 weeks. Information about hot flashes, quality of life, and toxicity were collected during these 4 weeks and compared with the baseline week.. After treatment with levetiracetam for 4 weeks (N = 19), mean hot flash scores (frequency times mean severity) were reduced by 57%, and mean hot flash frequencies were reduced by 53%, compared to the baseline week; both these reductions were greater than what would be expected with a placebo (20-25% reduction). There were significant improvements in abnormal sweating (p = 0.004), hot flash distress (p = 0.0002), and satisfaction of hot flash control (p = 0.0001), when comparing data from the fourth week of treatment to the baseline week. Twenty-nine percent of the subjects did not complete the study because of treatment-related adverse events, with the most frequently reported side effects being somnolence, fatigue, and dizziness, usually with mild to moderate intensity.. The results of this pilot trial suggest that levetiracetam might be an effective therapy for the treatment of hot flashes. Further data are needed to test this hypothesis, evaluating the efficacy and toxicity of this agent.

Topics: Breast Neoplasms; Dizziness; Fatigue; Female; Hot Flashes; Humans; Levetiracetam; Middle Aged; Nootropic Agents; Patient Satisfaction; Pilot Projects; Piracetam; Quality of Life; Severity of Illness Index; Sleep Stages

This multicenter, open-label study evaluated the short-term tolerability of intravenously (IV)-infused levetiracetam (LEV; 500-1,500 mg/100 ml, 15 min, b.i.d.) as a substitute for the same oral dose.. The study consisted of screening, 4-day IV LEV and 1-7 days of follow-up, and was conducted in 25 adults with partial-onset seizures receiving adjunctive oral LEV.. During the 4-day IV LEV, 11 (44%) subjects experienced at least one treatment-emergent adverse event (TEAE), with headache and fatigue being the most frequently reported. Five (20%) subjects experienced TEAEs considered to be related to the study drug. The tolerability profile was consistent with that of oral LEV, with all events judged mild or moderate in severity, no discontinuations, and no serious AEs or deaths reported. No AE related to seizure worsening was reported during IV LEV or brief follow-up.. LEV IV appears to be a well-tolerated, practical alternative in patients with partial-onset seizures temporarily unable to take the drug orally.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anticonvulsants; Drug Administration Schedule; Drug Therapy, Combination; Epilepsies, Partial; Fatigue; Female; Follow-Up Studies; Headache; Humans; Infusions, Intravenous; Levetiracetam; Male; Middle Aged; Piracetam; Treatment Outcome

The primary objective of this placebo-controlled study was to evaluate the safety and tolerability of levetiracetam (LEV) administered intravenously (IV) at higher doses and/or at a faster infusion rate than proposed. The secondary objective was to assess LEV pharmacokinetics.. Single ascending doses of LEV administered by IV infusion (2,000, 3,000, 4,000 mg over 15 min; 1,500, 2,000, 2,500 mg over 5 min) were evaluated in 48 healthy subjects in a randomized, single-blind, placebo-controlled study.. All randomized subjects completed the study. Adverse events reported after IV administration of LEV (

Topics: Administration, Oral; Adult; Anticonvulsants; Area Under Curve; Blood Pressure; Disorders of Excessive Somnolence; Dizziness; Dose-Response Relationship, Drug; Epilepsy; Fatigue; Female; Half-Life; Headache; Heart Rate; Humans; Infusions, Intravenous; Levetiracetam; Male; Piracetam; Placebos; Single-Blind Method; Time Factors

Topics: Analgesics, Non-Narcotic; Calcium Channel Blockers; Fatigue; Female; Herpes Zoster; Humans; Levetiracetam; Male; Neuralgia; Pilot Projects; Piracetam; Prospective Studies; Receptors, GABA; Receptors, Glycine; Treatment Outcome

To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy.. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed.. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009).. One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood.

Topics: Adult; Anticonvulsants; Epilepsy; Fatigue; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

In patients taking antiepileptic drugs (AEDs) for epilepsy, adverse effects (AEs) often lead to unfavorable quality of life, impaired adherence, and, eventually, discontinuation of pharmacological treatment. In a true-to-life sample of subjects from our academic epilepsy outpatient clinic, we aimed to identify predictors for overall high AE burden and for specific AEs focusing on patients on monotherapy.. All patients ≥16years of age with epilepsy for ≥12months were routinely asked to complete the Liverpool Adverse Event Profile (LAEP) just before their appointment. Demographic, epilepsy, and treatment variables were derived from our comprehensive outpatient database.. Out of 841 patients, 438 (61% female, mean age: 44.7±17.1years) on monotherapy were included in this study. Levetiracetam (n=151), lamotrigine (n=167), valproic acid (n=73), or controlled-release carbamazepine (n=47) were the most commonly used antiepileptic drugs (AEDs). Independent predictors for general high AE burden (LAEP score≥45) were duration of epilepsy, lack of 12-month seizure freedom, and partial epilepsy, but none of the four individual AEDs. The most frequent LAEP-defined specific AEs were sleepiness, difficulty concentrating, tiredness, and memory problems. The three most frequent independent predictors for each of the 19 AEs were lack of 12-month seizure freedom (13/19 AEs), individual AED (7/19 AEs), and partial epilepsy (6/19 AEs). Levetiracetam was independently associated with anger/aggression, nervousness/agitation, upset stomach, depression, and sleep disturbance; lamotrigine with nervousness/agitation, upset stomach, and difficulty concentrating; and valproic acid with upset stomach and shaky hands.. Individual AEDs independently predicted some specific AEs, but not overall high AE burden. Our findings may help to characterize patients with epilepsy who are at high risk for specific AEs. Dose reduction or change to another AED may reduce LAEP score and potential nonadherence.

Topics: Adult; Aged; Anticonvulsants; Anxiety; Carbamazepine; Depression; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Fatigue; Female; Humans; Lamotrigine; Levetiracetam; Male; Middle Aged; Piracetam; Quality of Life; Triazines; Valproic Acid; Young Adult

Levetiracetam is a frequently used drug in the therapy of partial onset, myoclonic and generalized tonic-clonic seizures. The main route of elimination is via the kidneys, which eliminate 66% of the unchanged drug as well as 24% as inactive metabolite that stems from enzymatic hydrolysis. Therefore dose adjustments are needed in patients with chronic kidney disease stage 5 D, i.e. patients undergoing dialysis treatment. In this patient population a dose reduction by 50% is recommended, so that patients receive 250-750 mg every 12 hours. However "dialysis" can be performed in using different modalities and treatment intensities. For most of the drugs pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis are not available. This is the first report on levetiracetam pharmacokinetics in a peritoneal dialysis patient.. A 73-y-old Caucasian male (height: 160 cm, weight 93 kg, BMI 36.3 kg/m2) was admitted with a Glasgow Coma Scale of 10. Due to diabetic and hypertensive nephropathy he was undergoing peritoneal dialysis for two years. Eight weeks prior he was put on levetiracetam 500 mg twice daily for suspected partial seizures with secondary generalization. According to the patient's wife, levetiracetam lead to fatigue and somnolence leading to trauma with fracture of the metatarsal bone. Indeed, even 24 hours after discontinuation of levetiracetam blood level was still 29.8 mg/l (therapeutic range: 12 - 46 mg/l). Fatigue and stupor had disappeared five days after discontinuation of the levetiracepam. A single dose pharamockinetic after re-exposure showed an increased half life of 18.4 hours (normal half life 7 hours) and levetiracetam content in the peritoneal dialysate. Both half-life and dialysate content might help to guide dosing in this patient population.. If levetiracetam is used in peritoneal dialysis patients it should be regularly monitored to avoid supratherapeutic levels that could lead to severe sequelae.

Topics: Aged; Anticonvulsants; Fatigue; Humans; Levetiracetam; Male; Metabolic Clearance Rate; Peritoneal Dialysis; Piracetam; Renal Insufficiency, Chronic; Seizures; Treatment Outcome