levetiracetam and Substance-Withdrawal-Syndrome

We describe a subset of patients with toxin-related precipitants of seizures/status epilepticus enrolled in the Established Status Epilepticus Treatment Trial (ESETT).. The ESETT was a prospective, double-blinded, adaptive trial evaluating levetiracetam, valproate, and fosphenytoin as second-line agents in benzodiazepine-refractory status epilepticus in adults and children. The primary outcome was the absence of seizures and improvement in the level of consciousness 1 hour after study drug administration. In this post hoc analysis, the safety and efficacy of second-line agents in a subset of patients with toxin-related seizures are described.. A total of 249 adults and 229 children were enrolled in the ESETT. Toxin-related seizures occurred in 29 (11.6%) adults and 1 child (0.4%). In adults, men were more likely to have toxin-related seizures than women (25 of 145, 17.2% versus 4 of 104, 3.9%). The most common toxin-related precipitants were alcohol withdrawal and cocaine, 11(37%) of 30 patients each. Cocaine was used with other substances by most patients 10 (91%) of 11, most commonly with an opioid 7 (64%) of 11. For alcohol withdrawal-related seizures, treatment successes with levetiracetam, valproate, and fosphenytoin were 3 (100%) of 3, 3 (50%) of 6, and 1 (50%) of 2, respectively. For cocaine-related seizures, treatment success was 1 (14%) of 7 for levetiracetam, 0 (0%) of 1 for valproate, and 1 (33%) of 3 for fosphenytoin. One patient who used cocaine and an opioid received fosphenytoin and developed life-threatening hypotension.. In the ESETT, approximately 1 in 10 adult patients with status epilepticus presented with a toxin-related seizure. Alcohol withdrawal and cocaine/opioid use were the most common toxin-related precipitants. Toxin-related benzodiazepine-refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of the patients.

Topics: Adult; Alcoholism; Analgesics, Opioid; Anticonvulsants; Benzodiazepines; Child; Cocaine; Female; Humans; Levetiracetam; Male; Phenytoin; Prospective Studies; Seizures; Status Epilepticus; Substance Withdrawal Syndrome; Valproic Acid

Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS.. One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale.. Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups.. Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Topics: Adult; Alcoholism; Anticonvulsants; Diazepam; Double-Blind Method; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Prospective Studies; Severity of Illness Index; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Adult; Alcoholism; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Male; Middle Aged; Nootropic Agents; Pilot Projects; Piracetam; Substance Withdrawal Syndrome

Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety.. The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV.. A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher's exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha=0.05).. The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p=0.28).. The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.

Topics: Adult; Anticonvulsants; Dibenzazepines; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Female; Humans; Levetiracetam; Male; Mental Disorders; Middle Aged; Psychiatric Status Rating Scales; Retrospective Studies; Seizures; Substance Withdrawal Syndrome; Treatment Outcome; Voltage-Gated Sodium Channel Blockers

Transient lesions of the splenium of the corpus callosum are characterized by MRI findings. The lesions are very rare, but significant from a clinical standpoint as differential diagnoses include serious conditions such as encephalitis, meningitis, and neuroleptic malignant syndrome. In addition, it is reported that some are attributed to the withdrawal of antiepileptic drugs. Here, we present a case of transient lesions of the splenium of the corpus callosum following rapid withdrawal of levetiracetam alone. To the best of our knowledge, this is the first report of such a case. Moreover, it is reported that cases of incidental transient lesions of the splenium of the corpus callosum are detected in Japan more often than in other countries, and as a result are prone to over-triage. Taking this into consideration, in the event of transient lesions of the splenium of the corpus callosum, the utmost attention must be paid to clinical symptoms and history relating to any of the aforementioned serious conditions.

Topics: Adolescent; Anticonvulsants; Corpus Callosum; Female; Humans; Levetiracetam; Magnetic Resonance Imaging; Piracetam; Substance Withdrawal Syndrome

Benzodiazepines are often considered the standard of care for managing symptoms of acute alcohol withdrawal syndrome. Because of potential adverse effects, other agents have been evaluated in this patient population. Previous studies have produced mixed results on the efficacy of levetiracetam in alcohol withdrawal.. The objective of this study was to determine whether adjunctive levetiracetam reduces the amount of symptom-triggered benzodiazepines required by patients experiencing symptoms of alcohol withdrawal.. We conducted a retrospective chart review of patients who experienced symptoms of alcohol withdrawal while hospitalized. The outcomes of patients who received adjunctive levetiracetam were compared with those of patients who received only the standard of care (control group).. Two hundred fifty patients (125 in each cohort) were included. No significant differences were found in the benzodiazepine requirements of the 2 cohorts. The control group required a median average daily dose of 2.0 mg of lorazepam (range, 0.1-17 mg/d) compared with the levetiracetam group, which required a median average daily dose of 1.3 mg of lorazepam (range, 0.0-53.5 mg/d) (P = 0.09). The patients in the control group required a median total of 6 mg of lorazepam during their hospitalization compared with a median total of 5.5 mg in the levetiracetam group. Both cohorts had a median length of stay of 3 days, although those in the levetiracetam group had a shorter length of intensive care unit stay and spent less time mechanically ventilated.. The adjunctive use of levetiracetam does not significantly reduce the benzodiazepine requirements of patients experiencing symptoms of alcohol withdrawal in the inpatient setting.

Topics: Adult; Alcoholism; Anticonvulsants; Benzodiazepines; Cohort Studies; Drug Therapy, Combination; Female; Hospitalization; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Substance Withdrawal Syndrome

Many recent researches have confirmed the effectiveness of antiepileptic drugs in preventing alcohol dependency, whereas our previous study showed that repeated treatment with topiramate, a new antiepileptic drug, was effective in increasing the plasma levels of beta-endorphin (an endogenous opioid peptide) in rats. It is well documented that in humans a genetic deficit of beta-endorphin is often associated with alcohol addiction as alcohol consumption elevates the level of this peptide. The aim of the present study is multifaceted: to investigate the effect of repeated treatment of levetiracetam (50 or 100mg/kg b.w., twice daily) on voluntary alcohol intake in alcohol preferring rats (Warsaw High Preferring; WHP) and to assess changes in plasma beta-endorphin levels while alcohol is available and when it is not available for an extended period of time. We observed a noticeable increase in the levels of beta-endorphin in rats with free access to alcohol whether in a prolonged levetiracetam-treated or vehicle-treated group. However, in the levetiracetam group, a voluntary intake of alcohol diminished in comparison with both the pretreatment period and in comparison with the vehicle-treated rats. A similar increase in the plasma beta-endorphin levels was observed in levetiracetam-treated rats that did not have access to ethanol. This finding lets us to believe that levetiracetam may be a promising medication in treatment of alcohol dependency as its application leads to the increase in the beta-endorphin concentration and ultimately results in reducing deficiency of this peptide.

Topics: Alcohol Drinking; Alcoholism; Animals; Anticonvulsants; beta-Endorphin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Ethanol; Female; Humans; Levetiracetam; Piracetam; Rats; Rats, Inbred Strains; Self Administration; Substance Withdrawal Syndrome

Optimal pharmacotherapy of the alcohol withdrawal syndrome (AWS) in outpatient settings is still a matter of discussion. The aim of this evaluation was to examine the efficacy and tolerability of a combination of levetiracetam and tiapride for outpatient alcohol detoxification.. This was an open-label evaluation. After screening eligibility for outpatient detoxification, 9 alcohol-dependent patients received levetiracetam and tiapride in a flexible dosage regimen up to 2500 and 300 mg/d, respectively, for a maximum of 7 days. Severity of alcohol withdrawal was assessed daily using the Alcohol Withdrawal Syndrome Scale (AWSS).. All patients completed the treatment successfully. The mean initial doses of levetiracetam and tiapride were 2166.7 and 300 mg/d, respectively. AWS as indicated by the AWSS score decreased clearly over 5 days. The combination of levetiracetam and tiapride was well tolerated. Neither treatment discontinuations because of side effects of the medication nor serious medical complications were observed during the detoxification.. The results of this evaluation provide first evidence that the combination of levetiracetam and tiapride might be an effective and safe treatment option for mild to moderate AWS in outpatient settings. Further randomized controlled trials are warranted to confirm these preliminary results.

Topics: Adult; Aged; Alcoholism; Dopamine Antagonists; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Nootropic Agents; Outpatients; Piracetam; Substance Withdrawal Syndrome; Tiapamil Hydrochloride; Treatment Outcome; Young Adult

A drug holiday seems to produce seizure interval prolongation (SIP) after reinstitution of antiepileptic drugs (AEDs). This effect was demonstrated mainly with carbamazepine. We evaluated SIP with newer AEDs and tested the relationship of SIP to history of AED tolerance.. We prospectively studied patients with refractory epilepsy admitted to the Vanderbilt epilepsy monitoring unit (EMU) over a period of 12 months. We included only patients on levetiracetam, lamotrigine, or oxcarbazepine who had their AEDs withdrawn on admission and reinstituted without change upon discharge. We defined SIP as the interval from EMU discharge to first seizure minus the interval between the last two seizures before EMU admission.. A total of 43 patients completed the study; 15 were on monotherapy. SIP was greater than zero in this patient group (p < 0.0001), with a mean prolongation of 19.4 +/- 28.0 days. The average SIP was higher (p = 0.01) in patients on monotherapy (29.7 +/- 23.8 days) than patients on polytherapy (13.9 +/- 29.0 days). SIP tended to be greater in patients with a prior history of AED tolerance (25.7 +/- 36.8 days) compared to patient with no prior history of AED tolerance (14.0 +/- 16.3 days).. SIP does occur after brief AED withdrawal. This effect is greater in patients on monotherapy and tends to be larger in patients with a history of AED tolerance. The SIP effect may be related to the phenomenon of tolerance, clinically seen as resistance to AED therapeutic effect.

Topics: Adult; Anticonvulsants; Carbamazepine; Drug Administration Schedule; Drug Resistance; Drug Tolerance; Electroencephalography; Epilepsy; Female; Follow-Up Studies; Humans; Lamotrigine; Levetiracetam; Male; Oxcarbazepine; Piracetam; Severity of Illness Index; Substance Withdrawal Syndrome; Treatment Outcome; Triazines

Anticonvulsant drugs are increasingly being used for alcohol detoxification in in- and outpatient settings. The aim of this study was to examine the efficacy, medical safety and mid-term outcome of levetiracetam, a drug with no marked liver toxicity, for outpatient alcohol detoxification.. This was an open-label observational study. After screening eligibility for outpatient alcohol detoxification, patients were seen daily for 5 days and received levetiracetam in a flexible dosage regime between 500 and 4 000 mg/d for a maximum of 7 days. Diazepam was used as a rescue medication. The severity of alcohol withdrawal was evaluated daily using the ALCOHOL WITHDRAWAL SYNDROME SCALE (AWSS). Mid-term treatment outcome was assessed at a 6-month follow-up.. A total number of 131 consecutively admitted alcohol-dependent patients received an outpatient detoxification treatment, 122 (93.1%) completed the programme successfully. The mean initial dose of levetiracetam was 1 850 mg/d. Alcohol withdrawal syndrome as indicated by the AWSS score decreased clearly over 5 days. Overall, the medication was well tolerated. There was no treatment discontinuations due to side effects of levetiracetam. No serious medical complications, especially seizures or deliria, were observed during the detoxification. At the 6-month follow-up, 57 patients (43.5%) were still abstinent. Patients with previous detoxifications had a significant higher risk for relapse (HR=1.88; p=0.016; CI 95%: 1.12-3.14) than patients without previous treatments.. The findings of this study provide some evidence that levetiracetam is an efficacious and safe treatment option for outpatient alcohol detoxification. Further randomised, controlled trials including mid- and long-term follow-ups are needed to confirm these findings.

Topics: Adolescent; Adult; Aged; Alcohol Drinking; Alcoholism; Ambulatory Care; Anticonvulsants; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Psychotherapy; Recurrence; Substance Withdrawal Syndrome; Temperance; Treatment Outcome; Young Adult

This case is the first report of a patient who had phenobarbital (PB) withdrawal seizures after having been seizure-free for 3 years following temporal lobe surgery. The patient had been taking PB for 14 years when a gradual taper of PB was started. When PB was at 60 mg/d, a titration of lamotrigine (LTG) was started. However, typical complex seizures occurred when the patient was on PB 60 mg/d, along with LTG 25mg/d. PB was increased back to 90 mg/d and levetiracetam (LEV) was titrated. Seizures appeared when the patient was on PB 30 mg/d and LEV 750 mg BID and continued for 3 weeks after PB was stopped and the patient was on LEV 1,000 mg BID. For the following 6 months, her aura frequency remained elevated in comparison to her baseline aura of two auras per month for the previous year before the start of the PB taper. She was followed for 24 months after her last PB withdrawal seizure. During the last 8 months, her aura frequency returned to her baseline. As suggested by animal studies, the PB withdrawal seizures and increase in aura frequency in this patient may be explained by changes in her levels of GABA(A) receptor subunits.

Topics: Anticonvulsants; Data Collection; Female; Humans; Lamotrigine; Levetiracetam; Middle Aged; Phenobarbital; Piracetam; Seizures; Substance Withdrawal Syndrome; Time Factors; Triazines

Some antiepileptic drugs have been used with success to counteract withdrawal symptoms following chronic use of sedatives, hypnotics or alcohol. We evaluated the potential of levetiracetam (Keppra), a new antiepileptic drug, to prevent benzodiazepine withdrawal in an animal model sensitive to the anxiogenic effect resulting from drug cessation. The effects of levetiracetam (17 and 54 mg/kg) given intraperitoneally (i.p.) were determined on anxiety induced in female NMRI mice by withdrawal from 21 days of chronic administration of chlordiazepoxide. Administration of chlordiazepoxide was i.p. twice daily, in increments of 2 mg/kg, from 10 up to 40 mg/kg. Anxiety was evaluated using an elevated plus-maze test 24-h after chlordiazepoxide withdrawal. Discontinuation of chronic chlordiazepoxide induced a significant anxiogenic profile in the plus-maze test mainly characterised by a decrease in open arm exploration. This effect was dose-dependently prevented by administration of levetiracetam during the withdrawal period. The highest dose tested (54 mg/kg) induced statistically significant effects on all variables recorded but had no effect upon plus-maze exploration in normal mice. This suggests that the observed effects are dependent upon the level of stress or anxiety of the animals. These results support potential efficacy of levetiracetam in the benzodiazepine withdrawal syndrome.

Topics: Analysis of Variance; Animals; Anti-Anxiety Agents; Anticonvulsants; Anxiety; Chlordiazepoxide; Dose-Response Relationship, Drug; Female; Levetiracetam; Maze Learning; Mice; Mice, Inbred Strains; Piracetam; Substance Withdrawal Syndrome

Levetiracetam (LEV) is an interesting novel antiepileptic drug with proven efficacy in both animal models and patients with partial epilepsy. To study whether the efficacy of the drug changes during chronic treatment, we evaluated the anticonvulsant activity of LEV during prolonged daily administration in amygdala-kindled rats.. On the basis of the anticonvulsant potency and duration of action after acute doses, LEV was administered in fully kindled rats three times daily at 108 mg/kg i.p. for 3 weeks. For the study of anticonvulsant efficacy, the afterdischarge threshold was determined before, during, and after the drug treatment period. To determine whether the pharmacokinetics of the drug change during prolonged treatment, LEV levels were repeatedly determined in plasma during the treatment period.. LEV markedly increased the afterdischarge threshold and decreased the seizure severity and duration after initial dosing, but a marked loss of anticonvulsant efficacy developed during chronic treatment. This loss of efficacy was not due to alterations in drug elimination, indicating the development of functional tolerance to LEV during repeated administration. After the termination of treatment, no withdrawal signs (e.g., changes in behavior, body temperature, body weight, or seizure threshold) were observed.. The data demonstrate that chronic administration of LEV leads to a significant reduction in anticonvulsant efficacy in the kindling model of temporal lobe epilepsy. Whether this experimental observation has clinical relevance must await monotherapy trials with long-term follow-up of patients who initially responded to LEV.

Topics: Amygdala; Animals; Anticonvulsants; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Tolerance; Epilepsy, Temporal Lobe; Female; Kindling, Neurologic; Levetiracetam; Piracetam; Rats; Rats, Wistar; Substance Withdrawal Syndrome