levetiracetam and Neuralgia

Antiepileptic drugs have been used in pain management since the 1960s; some have shown efficacy in treating different neuropathic pain conditions. The efficacy of levetiracetam for relief of neuropathic pain has not previously been reviewed.. To assess the analgesic efficacy and adverse events of levetiracetam in chronic neuropathic pain conditions in adults.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6) (via the Cochrane Library), MEDLINE, EMBASE, and two clinical trials databases (ClinicalTrials.gov. and the World Health Organisation Clinical Trials Registry Platform) to 3 July 2014, together with reference lists of retrieved papers and reviews.. We included randomised, double-blind studies of two weeks duration or longer, comparing levetiracetam with placebo or another active treatment in adults with chronic neuropathic pain conditions. Studies had to have a minimum of 10 participants per treatments arm.. Two review authors independently extracted efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction; intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison; 8 to 12 weeks duration; parallel design); second tier evidence from data that failed to meet one or more of these criteria and that we considered at some risk of bias but with at least 200 participants in the comparison; and third tier evidence from data involving fewer than 200 participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both.. We included six studies: five small, cross-over studies with 174 participants, and one parallel group study with 170 participants. Participants were treated with levetiracetam (2000 mg to 3000 mg daily) or placebo for between four and 14 weeks. Each study included participants with a different type of neuropathic pain; central pain due to multiple sclerosis, pain following spinal cord injury, painful polyneuropathy, central post-stroke pain, postherpetic neuralgia, and post-mastectomy pain.None of the included studies provided first or second tier evidence. The evidence was very low quality, downgraded because of the small size of the treatment arms, and because studies reported results using last observation carried forward (LOCF) imputation for withdrawals or using only participants who completed the study according to the protocol, where there were greater than 10% withdrawals. There were insufficient data for a pooled efficacy analysis in particular neuropathic pain conditions, but individual studies did not show any analgesic effect of levetiracetam compared with placebo. We did pool results for any outcome considered substantial pain relief (≥ 50% pain intensity reduction or 'complete' or 'good' responses on the verbal rating scale) for four studies with dichotomous data; response rates across different types of neuropathic pain was similar with levetiracetam (10%) and placebo (12%), with no statistical difference (risk ratio 0.9; 95% confidence interval (CI) 0.4 to1.7).We pooled data across different conditions for adverse events and withdrawals. Based on very limited data, significantly more participants experienced an adverse event with levetiracetam than with placebo (number needed to treat for an additional harmful event (NNH) 8.0 (95% CI 4.6 to 32)). There were significantly more adverse event withdrawals with levetiracetam (NNH 9.7 (6.7 to 18)).. The amount of evidence for levetiracetam in neuropathic pain conditions was very small and potentially biased because of the methods of analysis used in the studies. There was no indication that levetiracetam was effective in reducing neuropathic pain, but it was associated with an increase in participants who experienced adverse events and who withdrew due to adverse events.

Topics: Adult; Analgesics; Chronic Disease; Humans; Levetiracetam; Neuralgia; Piracetam; Randomized Controlled Trials as Topic

Central post-stroke pain (CPSP) is a severe chronic neuropathic pain condition defined as a spontaneous pain or allodynia corresponding to a vascular lesion. It usually evolves weeks after stroke, and can distinctively impair the quality of life. Treatment is complex and mostly unsatisfactory. We hypothesized that the anti-epileptic drug levetiracetam (LEV) improves CPSP compared with placebo. The purpose of this study was to examine the efficacy and tolerability of LEV in patients with CPSP.. In a double-blind, placebo-controlled, crossover study design patients with CPSP lasting at least 3 months and a pain score ≥ 4 on the 11-point Likert scale were treated over two 8-week periods with a maximum dose up to 3000 mg LEV or placebo. Primary endpoint was a median pain lowering ≥ 2 in the final treatment week compared with the last baseline week. Secondary outcome measures comprised additional pain ratings, depression, sleep quality, quality of life and patients' global impression of change.. Of 42 patients, 33 [61.5 years (40-76); 38% women] completed the study. Side effects and withdrawals were more frequent in the LEV (n = 5) group than in the placebo group (n = 1). Patients treated with LEV did not show any improvement of pain or changes in secondary outcome parameters compared with placebo.. LEV is not effective in treatment for CPSP. The mode of action of LEV does not exert an analgesic effect in chronic CPSP.

Topics: Adult; Aged; Anticonvulsants; Cross-Over Studies; Double-Blind Method; Female; Humans; Levetiracetam; Male; Middle Aged; Neuralgia; Pain Measurement; Piracetam; Placebos; Stroke

Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signalling in the pain pathway. The aim of this study was to test the analgesic effect of levetiracetam in central pain in multiple sclerosis. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with multiple sclerosis, symptoms and signs complying with central neuropathic pain and pain symptoms for more than 6 months, as well as pain intensity of more than 4 on a 0 to 10-point numeric rating scale were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale. Eighty-nine patients were screened for participation and 30 patients entered the study. Twenty-seven patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.4 vs. placebo 2.1, p = 0.169), total pain intensity (levetiracetam 5.3 vs. placebo 5.7, p = 0.147) or any of the other outcome measures (p = 0.086-0.715) in the total sample of patients. However, there was significant reduction of pain, increased pain relief and/or more favourable pain relief with levetiracetam than with placebo in patients with lancinating or without touch-evoked pain (p = 0.025-0.046). This study found no effect of the anticonvulsant levetiracetam in non-selected patients with central pain in multiple sclerosis, but an effect in subgroups with specific pain symptoms was indicated.

Topics: Adult; Analgesics; Anticonvulsants; Chronic Pain; Cross-Over Studies; Female; Humans; Hyperalgesia; Levetiracetam; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Pain Threshold; Patient Satisfaction; Piracetam; Placebos; Treatment Failure

Levetiracetam is an anticonvulsant which is assumed to act by modulating neurotransmitter release via binding to the vesicle protein SV2A. This could have an impact on signaling in the nociceptive system, and a pilot study indicated relief of neuropathic pain with levetiracetam.. The aim of this study was to test the analgesic effect of levetiracetam in painful polyneuropathy.. This was a randomized, double-blind, placebo-controlled, cross-over trial with levetiracetam 3000 mg/day versus placebo (6-week treatment periods). Patients with diagnosed polyneuropathy and symptoms for more than 6 months, age between 20 and 80 years, pain intensity of more than 4 on a 0-10-point numeric rating scale, and pain at least 4 days a week were included in the study. The primary outcome measure was pain relief at the end of each treatment period as measured on a 6-point verbal scale.. Ninety-three patients were screened for participation and 39 patients entered the study. Thirty-five patients were included in the data analysis. There were no differences in the ratings of pain relief (levetiracetam 2.29 versus placebo 2.28, p=0.979), total pain intensity (levetiracetam 5.5 versus placebo 5.3, p=0.293) or any of the other outcome measures (p=0.147-1.00).. This study indicates that the anticonvulsant levetiracetam has no clinically relevant effect on painful polyneuropathy.

Topics: Adult; Aged; Anticonvulsants; Cross-Over Studies; Double-Blind Method; Female; Humans; Levetiracetam; Male; Middle Aged; Neuralgia; Pain Measurement; Piracetam; Polyneuropathies; Treatment Outcome

Central neuropathic pain (CNP) is a prevalent and distressing symptom in patients with multiple sclerosis (MS). The anticonvulsant levetiracetam (LEV) has been shown to be efficacious in some types of CNP, but its efficacy in MS-related CNP has not been confirmed.. To investigate the tolerability and potential effects of LEV against CNP in MS subjects, we performed a single-center, prospective, randomized, single-blind, placebo-controlled study in twenty patients with MS and CNP. Outcomes before and during the 3-month study were assessed using validated measures of pain, depression, disability and quality of life.. The medication was well tolerated and analysis revealed a significant difference between the LEV and placebo arm in all study outcomes related to pain (mean pain intensity score, mean pain difference, percentage of patients with a clinically significant pain reduction). Furthermore, the individual quality of life rating improved in treated patients, showing a significant correlation with pain reduction.. These findings suggest that further studies with larger samples of patients be carried out in order to confirm the efficacy of LEV in MS-related CNP population.

Topics: Adult; Analgesics; Anticonvulsants; Depression; Disability Evaluation; Female; Humans; Levetiracetam; Male; Middle Aged; Multiple Sclerosis; Neuralgia; Pain Measurement; Pilot Projects; Piracetam; Quality of Life; Surveys and Questionnaires; Treatment Outcome; Young Adult

The aim of this randomized, double-blind, placebo-controlled, cross-over study was to test whether levetiracetam relieves the postmastectomy pain syndrome (PMPS).. Postmastectomy pain syndrome was defined as pain of neuropathic character located in the area of the surgery and/or the ipsilateral arm. The inclusion criteria were: age more than 18 years, characteristic symptoms corresponding to PMPS more than 6 months after surgery for breast cancer, pain duration more than 3 months, peripheral nerve lesions confirmed by abnormal neurological and quantitative sensory tests, intensity of pain more than 4 on a numeric rating scale from 0 to 10 and pain present at least 4 days a week.. Forty-nine patients were screened for participation and 27 patients were included in the study. Twenty-five patients completed two treatment phases of 4 weeks duration with levetiracetam (3000 mg/day) and placebo. There was no difference in the rating of pain relief between treatment with levetiracetam (P = 0.83) and placebo nor when adjusted for possible period effect (P = 0.60). Analysis defining response as pain relief more than 4 on an eleven-point numeric rating scale showed no significant difference between treatment with levetiracetam and placebo (P = 1.00).. Levetiracetam apparently does not relieve peripheral neuropathic pain in PMPS.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Double-Blind Method; Female; Humans; Levetiracetam; Mastectomy; Middle Aged; Neuralgia; Pain, Postoperative; Piracetam

Levetiracetam is a new antiepileptic drug. There is only limited experience with levetiracetam in clinical neuropathic pain.. To test the analgesic effect of levetiracetam in a human experimental pain model in order to obtain preclinical evidence for its potential effect in neuropathic pain.. Sixteen healthy volunteers completed a randomized, double-blind, cross-over trial with a single oral dose of 1500 mg levetiracetam against placebo. Pain tests included pain detection and tolerance to single electrical stimulation and temporal pain summation threshold to repetitive electrical stimulation (3 Hz) of the sural nerve.. Levetiracetam significantly increased the pain tolerance thresholds (p=0.04), and the pain detection thresholds tended to be increased (p=0.06), whereas levetiracetam had no effect on temporal pain summation thresholds (p=0.30).. Levetiracetam has an analgesic effect in the electrical sural nerve stimulation pain model, but it did not increase temporal pain summation threshold. Levetiracetam may still be effective in clinical neuropathic pain.

Topics: Adult; Anticonvulsants; Cross-Over Studies; Double-Blind Method; Electric Stimulation; Female; Humans; Levetiracetam; Male; Neuralgia; Pain Threshold; Piracetam; Reaction Time; Sural Nerve

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

Topics: Anticonvulsants; Diabetic Neuropathies; Humans; Levetiracetam; Neuralgia; Piracetam; Quality of Life; Symptom Assessment; Treatment Failure

Pharmacological treatment is the first that should be taken into account in dealing with neuropathic pain, antiepileptic drugs being one of the leading options. Levetiracetam is a state of the art antiepileptic drug that has displayed antinociceptive activity in experimental models of pain and clinical effectiveness as an analgesic in series of patients with neuropathic pain.. To analyse the effectiveness of levetiracetam as an analgesic in the treatment of neuropathic pain by means of a systematic review of the literature.. The Medline/PubMed database was used in the study and the search criteria included three fundamental elements: levetiracetam, neuropathic pain and patients. The studies identified were those published before 31st January 2011. The selected studies were submitted to a quality analysis according to the Physiotherapy Evidence Database scale (0-10).. Three series of cases, two open non-controlled pilot studies and four randomised clinical trials (RCT) were selected. Only the RCT met acceptable quality criteria. The aetiology of the neuropathic pain was different in each of the RCT analysed. Levetiracetam proved to be effective in the treatment of neuropathic pain in the studies with a low level of methodological quality (case series and pilot studies) and in one RCT aimed at patients with central neuropathic pain due to multiple sclerosis.. Few clinical trials with a high level of methodological quality have been conducted to evaluate the effectiveness of levetiracetam in the treatment of neuropathic pain and most of those that have been carried out do not show any benefit in comparison to the use of a placebo.

Topics: Anticonvulsants; Clinical Trials as Topic; Humans; Levetiracetam; Neuralgia; Piracetam; PubMed; Review Literature as Topic; Treatment Outcome

Chemical modifications of dimiracetam, a bicyclic analogue of the nootropic drug piracetam, afforded a small set of novel derivatives that were investigated in in vivo models of neuropathic pain. Compounds 5, 7 and 8 displayed a very promising antihyperalgesic profile in rat models of neuropathic pain induced by both chronic constriction injury of the sciatic nerve and streptozotocin. The compounds completely reverted the reduction of pain threshold evaluated by the paw pressure test. Importantly these derivatives did not induce any behavioural impairment as evaluated by the rotarod test. These results suggest that compounds 5, 7 and 8 might represent novel and well-tolerated therapeutic agents for the relief of neuropathic pain.

Topics: Animals; Behavior, Animal; Disease Models, Animal; Imidazoles; Neuralgia; Pain Threshold; Pyrroles; Rats; Structure-Activity Relationship