levetiracetam and Alcoholism

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

Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers.. In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16.. No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001).. This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.

Topics: Adult; Affect; Aged; Alcoholism; Anticonvulsants; Anxiety; Breath Tests; Delayed-Action Preparations; Depression; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Patient Compliance; Piracetam; Quality of Life; Socioeconomic Factors; Treatment Outcome

Levetiracetam (Keppra) is a commonly prescribed anticonvulsant that has been shown to attenuate alcohol consumption in an open-label study of treatment-seeking, alcohol-dependent subjects.. Here we performed a 42-day placebo-controlled, double-blind, randomized crossover trial to evaluate the effects of levetiracetam on moderate to heavy drinkers receiving either a low (500-1000 g/d) or a moderate (1000-2000 g/d) dose. Electronic diaries were used to monitor daily ethanol intake.. Across the entire group, there was no effect of levetiracetam on drinking irrespective of dose, treatment order, family history, ethnicity, sex, or adverse effects. However, a median split of the data based on the number of drinks consumed while taking placebo revealed that levetiracetam significantly increased drinking in the lower drinking subjects (n = 23, P = 0.05, t = 2.07) while having no effect on drinking in the higher half (n = 23, P = 0.75, t = 0.32). Preliminary stratification based on common polymorphisms associated with alcoholism and impulsivity indicated that subjects with alcoholism-associated alleles may drink even more while taking levetiracetam.. Our data suggest that levetiracetam is not an appropriate treatment for non-treatment seeking alcohol abusers and can, in fact, increase their consumption of alcohol.

Topics: Alcohol Drinking; Alcoholism; Anticonvulsants; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Levetiracetam; Male; Piracetam

Antiepileptics have been shown to reduce alcohol intake or to prevent relapse in patients with alcoholism.. To investigate if the new antiepileptic levetiracetam (LEV) prevents relapse after detoxification compared with placebo in patients with alcohol dependence.. Two hundred one patients were included in the prospective, randomized, double-blind, multicenter, placebo-controlled trial. After detoxification treatment and a screening period of 7 days, patients were randomized to treatment with LEV or placebo. Medication was administered in a fixed-dose schedule for 16 weeks. Primary outcome parameters were the overall rate and time to relapse with heavy drinking. Secondary outcome parameters were time to the first drink, craving, adherence, tolerability, and safety data (mean corpuscular volume, serum alanine aminotransferase, serum aspartate aminotransferase, γ-glutamyltransferase).. The rate of relapse and the time to relapse did not differ significantly between both groups, but less patients treated with LEV terminated treatment early compared with patients receiving placebo. Tolerability and safety data were similar in the LEV group compared with placebo.. Our data do not support a significant effect of LEV on relapse prevention in patients with alcohol dependence during the first 16 weeks of abstinence.

Topics: Adolescent; Adult; Aged; Alcoholism; Anticonvulsants; Behavior, Addictive; Female; Humans; Levetiracetam; Male; Medication Adherence; Middle Aged; Piracetam; Secondary Prevention

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

The aim of this open-label pilot study was to assess the efficacy and safety of the novel anticonvulsant agent, levetiracetam, for the treatment of alcohol dependence. A maximal dose of 2000 mg was administered daily for 10 weeks to alcohol dependent subjects (n = 20). Mean reported ethanol intake declined significantly from 5.3 to 1.7 standard drinks per day. Levetiracetam was well tolerated by most subjects.

Topics: Alcoholism; Anticonvulsants; Brain; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Receptors, AMPA; Receptors, GABA-A; Receptors, Glycine

Alcohol dependence is frequently associated with anxiety disorders. The exact nature of the relationship between alcohol dependence and anxiety disorders is unknown, but emerging evidence suggests that in a majority of cases, the anxiety disorder is independent of the alcohol use disorder. There is pre-clinical and clinical evidence that levetiracetam, a newer generation anticonvulsant medication, may be efficacious in the treatment of co-occurring alcohol use and anxiety disorders.. In an open label clinical trial, three patients with alcohol dependence and a co-morbid anxiety disorder were treated with levetiracetam in doses up to 1500 mg twice daily for up to 8 weeks.. All three participants reported reductions in alcohol consumption and anxiety symptoms during the study period. Levetiracetam was generally well tolerated.. This study suggests that levetiracetam deserves further study in the treatment of alcohol dependence and co-occurring anxiety disorders.

Topics: Adult; Alcohol Drinking; Alcoholism; Anxiety Disorders; Diagnosis, Dual (Psychiatry); Female; Humans; Levetiracetam; Male; Middle Aged; Nootropic Agents; Piracetam

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

Topics: Aged; Alcoholism; Anticonvulsants; Autoantibodies; Cognition Disorders; Epilepsy, Generalized; Humans; Levetiracetam; Limbic Encephalitis; Magnetic Resonance Imaging; Male; Neurosyphilis; Piracetam; Thiamine; Vitamins

Levetiracetam exhibited 2 promising results in preclinical studies as well as in treating alcohol withdrawal in humans. Two open-label trials suggested that levetiracetam may be efficient in alcohol-related disorder.. The study by Fertig and colleagues (2012) examines the effects of levetiracetam using a double-blind, placebo-controlled design including 130 participants. Fertig and colleagues' study included alcohol-dependent participants drinking heavily. Double-blind medication was dispensed for 16 weeks, with a target dose of 2,000 mg per day from week 5 to week 14, and then tapered.. The results are negative both on the primary and on the secondary outcomes, except from lower alcohol-related consequences in the levetiracetam extended-release (XR) group, and a trend for a lower quality of life in the levetiracetam XR group. These last 2 results would have been nonsignificant after controlling for multiple testing.. By conducting a state-of-the-art randomized-controlled clinical trial with negative results, Fertig and colleagues have filled an important gap in the existing literature.

Topics: Alcoholism; Anticonvulsants; Baclofen; Double-Blind Method; GABA Agonists; Humans; Levetiracetam; Piracetam; Quality of Life; Randomized Controlled Trials as Topic

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

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