levetiracetam and Peripheral-Nervous-System-Diseases

Oxcarbazepine, topiramate, zonisamide, and levetiracetam are the antiepileptic drugs (AEDs) most recently approved by the US Food and Drug Administration. Based on the experience with carbamazepine, gabapentin, and lamotrigine, these newer AEDs are being investigated for the management of neuropathic pain.. This article reviews preclinical and clinical data on the efficacy and tolerability of these 4 AEDs in the management of neuropathic pain, as well as the pharmacokinetics, drug-interaction potential, adverse effects, and dosing of these agents, with an emphasis on their use in older individuals.. Relevant studies were identified through a MEDLINE search of the Englidh-language literature published between 1986 and May 2003, a review of the reference lists of identified articles, and abstracts from the annual meetings of the American Academy of Neurology (1986-2002) and the 2003 Annual Meeting of the American Pain Society. Search terms were oxcarbazepine, topiramate, zonisamide, and levetiracetam.. Oxcarbazepine and topiramate have been effective in animal models of neuropathic pain. Thirty-four publications on the efficacy and tolerability of the 4 agents were identified (25 case reports/case series, 6 randomized parallel-group studies, and 3 randomized crossover studies). The 9 randomized studies were restricted to oxcarbazepine and topiramate, and 23 (68%) publications were available in abstract form only. These preliminary data suggest that the 4 newer AEDs may be useful in a wide variety of neuropathic pain syndromes; however, additional data, including full-length peer-reviewed reports, are necessary before their true analgesic potential in neuropathic pain can be determined. All 4 agents have pharmacodynamic interactions with other psychotherapeutic drugs, potentiating adverse central nervous system events such as sedation. With the exception of levetiracetam, these drugs also have pharmacokinetic interactions with other drugs, although to a somewhat lesser extent than carbamazepine. These agents have some unique adverse effects not frequently monitored by clinicians, such as hyponatremia, nephrolithiasis, acute myopia with secondary angle-closure glaucoma, and weight loss.. Based on preliminary data, oxcarbazepine, topiramate, zonisamide, and levetiracetam may be useful in the treatment of a wide variety of neuropathic pain syndromes, although full publication of the results of controlled trials is awaited. These agents are associated with specific adverse effects not commonly monitored by clinicians. Of the 4, levetiracetam appears to be easiest to use (ie, no need for dose adjustment in organ dysfunction, no need for laboratory monitoring) and best tolerated, and has not been associated with the unique toxicities seen with oxcarbazepine, topiramate, and zonisamide. The ultimate role of these agents in the therapeutic armamentarium against pain requires further research and experience. In the interim, these 4 agents should be used to treat neuropathic pain in the elderly only when carbamazepine, gabapentin, or lamotrigine cannot be used or when the response to the aforementioned agents is suboptimal.

Topics: Aged; Analgesics, Non-Narcotic; Animals; Carbamazepine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Fructose; Humans; Isoxazoles; Levetiracetam; Oxcarbazepine; Pain; Peripheral Nervous System Diseases; Piracetam; Topiramate; Zonisamide

Certain types of pain associated with cancer may be difficult to treat with standard therapies, often resulting in intractable pain and suffering for the patient. The use of an opioid as analgesic monotherapy can lead to poorly controlled pain as well as multiple side effects. Non-opioid adjunctive analgesics, such as antidepressants and antiepileptic drugs (AEDs) often improve both pain control, and side effect prevalence. Levetiracetam is an AED with unique mechanisms of action that may have analgesic properties in various pain syndromes. Seven patients with neoplasms involving neural structures (four invading the brachial plexus, and three the lumbosacral plexus) had severe pain of 8 to 9 out of 10 on a visual analog scale (VAS), despite the use of parenteral opioids and various adjunctive therapies. These patients were treated with oral levetiracetam titrated over days to two weeks, depending on the location of pain, drug response, and tolerance to tapering of opioid analgesics. Opioid and adjunctive analgesic use and VAS scores were recorded periodically. The maximum levetiracetam dose ranged from 500 mg to 1500 mg BID. All patients experienced pain control improvement after the addition of levetiracetam, with VAS scores decreasing from 8-9 out of 10 to 0-3 out of 10 within two to 14 days of therapy initiation. Overall opioid use decreased by at least an estimated 70%, without drug related adverse events. In this small series of patients, levetiracetam effectively and safely improved pain relief in patients with neoplastic plexopathies previously resistant to standard analgesic approaches.

Topics: Adult; Aged; Analgesics, Opioid; Anticonvulsants; Brachial Plexus Neuropathies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Levetiracetam; Lumbosacral Plexus; Male; Middle Aged; Neoplasms; Pain; Peripheral Nervous System Diseases; Piracetam

The purpose of this study was to assess, in rats, the antinociceptive effects of levetiracetam (i.p.), a novel antiepileptic drug, in acute pain tests and in two models of human neuropathic pain. Levetiracetam and carbamazepine contrasted morphine by an absence of effect in the tail flick and hot plate tests. In normal rats, carbamazepine failed to modify the vocalisation thresholds to paw pressure whereas levetiracetam slightly increased this threshold only at the highest dose (540 mg/kg) for 30 min. In the sciatic nerve with chronic constriction injury model, the highest dose of levetiracetam (540 mg/kg) and carbamazepine (30 mg/kg) reversed the hyperalgesia. In streptozocin-induced diabetic rats, levetiracetam dose-dependently increased the vocalization threshold from 17 to 120 mg/kg reaching a similar effect as 10 mg/kg of carbamazepine. These results indicate that levetiracetam induces an antihyperalgesic effect in two models of human neuropathic pain, suggesting a therapeutic potential in neuropathic pain patients.

Topics: Acute Disease; Analgesics; Animals; Carbamazepine; Chronic Disease; Constriction, Pathologic; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hyperalgesia; Injections, Intraperitoneal; Levetiracetam; Male; Morphine; Pain; Pain Measurement; Peripheral Nervous System Diseases; Piracetam; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Vocalization, Animal

Topics: Acetaminophen; Acetates; Amines; Analgesics; Animals; Cyclohexanecarboxylic Acids; Disease Models, Animal; Drug Delivery Systems; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Levetiracetam; Nitrates; Pain; Peripheral Nervous System Diseases; Piracetam; Pregabalin; Topiramate