levetiracetam and Bipolar-Disorder

Topics: Anticonvulsants; Bipolar Disorder; Humans; Levetiracetam

The anticonvulsants valproate and carbamazepine have efficacy in treating acute mania, but their efficacy in treating acute bipolar depression and preventing mood episodes remains uncertain. Despite this, and given their utility and widespread use, both are widely accepted as standard treatments for bipolar disorder. All the newer anticonvulsants that have become available during the last decade have been or are being assessed to determine their efficacy in the treatment of various phases of bipolar disorder. Among the newer anticonvulsants, some appear to have efficacy in treating core bipolar symptoms, while others have efficacy in treating psychiatric comorbidity such as substance abuse or an anxiety disorder. Lamotrigine is the most widely studied and is effective in treating and preventing bipolar depression, and it is the only anticonvulsant approved by the U.S. Food and Drug Administration as a maintenance treatment for bipolar disorder. Other newer anticonvulsants, levetiracetam, oxcarbazepine, phenytoin, and zonisamide offer promise, but further studies are required before they can be recommended for routine use to treat bipolar disorder. Gabapentin and topiramate do not appear to have efficacy in treating acute mania, but their utility in bipolar depression and prevention of mood episodes has not been studied in double-blind trials. Pregabalin has utility in treating generalized anxiety disorder, but it has not been studied in bipolar disorder. Given the success of lamotrigine in treating bipolar disorder, further double-blind controlled trials of the newer anticonvulsants in treating bipolar disorder are warranted. This article summarizes current evidence from trials of anticonvulsants in bipolar disorder and makes recommendations for their clinical use.

Topics: Acetates; Amines; Anticonvulsants; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Depressive Disorder; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Isoxazoles; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Phenytoin; Piracetam; Pregabalin; Tiagabine; Topiramate; Treatment Outcome; Triazines; Zonisamide

Unsatisfactory responses to bipolar disorder treatments have necessitated novel therapeutic approaches. Evidence of levetiracetam's effectiveness in mania was reported in previous studies. This study evaluated its efficacy, safety and tolerability as an adjunct to quetiapine in mania. Forty-four patients with Young Mania Rating Scale (YMRS) score ≥20 entered and were randomized to receive levetiracetam plus quetiapine or placebo plus quetiapine for 6 weeks. Patients were assessed using the YMRS and Beck Scale for Suicidal Ideations (BSSI) at baseline and weeks 2, 4 and 6. Changes in the scores, remission rates and response to treatment were compared between the groups. Forty patients completed the trial. The general linear model (GLM) repeated measures demonstrated a significant effect for time × treatment interaction on the YMRS score during the trial (P = 0.04). A greater reduction in YMRS scores was seen in the levetiracetam group compared with the placebo group from baseline to week 4 (P = 0.045). Response to treatment was significantly better in the levetiracetam group (P = 0.046). No significant effect for time × treatment interaction on BSSI score was seen in GLM repeated measures. Finally, there was no significant difference in the frequency of adverse events. Adjunctive levetiracetam is effective, safe and well-tolerated in patients with mania. Further high-quality, large-scale trials are recommended.

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Double-Blind Method; Humans; Levetiracetam; Mania; Psychiatric Status Rating Scales; Quetiapine Fumarate; Treatment Outcome

Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania.. A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study.. Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition.. Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Double-Blind Method; Female; Humans; Levetiracetam; Lithium; Male; Mania; Psychiatric Status Rating Scales; Treatment Outcome

To study the efficacy of adjunctive levetiracetam therapy compared with placebo in the treatment of subjects with depression with bipolar disorder.. This double-blind, placebo-controlled clinical trial randomly assigned outpatients with bipolar disorder type I and type II who were experiencing a major depressive episode (Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version criteria) to treatment with either placebo or adjunctive levetiracetam (up to 2,500 mg/d flexibly dosed) for 6 weeks. The subjects were recruited from October 2005 to June 2008. The primary efficacy measure was mean change from baseline to week 6 in the Hamilton Depression Rating Scale (21-item). Secondary efficacy assessments included the Montgomery-Åsberg Depression Rating Scale, the Beck Depression Inventory, the Clinical Global Impressions-Bipolar Version scale, the Hamilton Anxiety Rating Scale, and the Young Mania Rating Scale.. Of 42 subjects randomly assigned to placebo or drug, 32 received at least 1 postbaseline assessment and thus were included in the analysis. The mean (SD) levetiracetam daily dose at endpoint evaluation was 1,132 (425) mg/d. There was no significant difference in the mean change from baseline to week 6 in the Hamilton Depression Rating Scale scores for levetiracetam compared with placebo. There were no significant differences in any of the secondary outcome measures.. Levetiracetam adjunctive therapy was not superior to placebo in the short-term treatment of subjects with depression with bipolar disorder in the population studied.. Clinicaltrials.gov Identifier: NCT00566150.

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Double-Blind Method; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome

Topics: Anticonvulsants; Bipolar Disorder; Drug Therapy, Combination; Humans; Levetiracetam; Piracetam; Psychiatric Status Rating Scales; Valproic Acid

Topics: Aged; Alzheimer Disease; Bipolar Disorder; Female; Humans; Levetiracetam; Male; Nootropic Agents; Pilot Projects; Piracetam; Psychiatric Status Rating Scales

Levetiracetam is a recently approved, well-tolerated anticonvulsant with a unique mechanism of action yielding efficacy in treatment-refractory seizure disorders and positive effects in an animal model of mania. Given the effectiveness of a range of other anticonvulsants in bipolar disorder, we sought to evaluate levetiracetam in patients with treatment-resistant illness.. Thirty-four patients received 500 to 1000 mg of levetiracetam titrated to a target dose of 2000 mg/day (maximum dose = 3000 mg/day) as open, adjunctive treatment for clinically significant symptoms of depression (N = 13), mania (N = 7), or cycling (N = 14) despite ongoing treatment with mood stabilizers. Inventory for Depressive Symptomatology-Clinician version (IDS-C), Young Mania Rating Scale (YMRS), and Clinical Global Impressions scale for use in Bipolar Illness ratings were completed at each visit for 8 weeks, and partial responders were offered continuation treatment. Data were collected from July 2001 to December 2002.. Five of 16 (31%; 13 depressed, 3 cycling) patients with initial depressive symptoms met the criterion for remission (IDS-C score of < or = 13) at last observation. All of these patients were less severely ill at baseline, whereas none of those more severely depressed at baseline responded. The majority of the 16 patients (7 manic, 9 cycling) with manic symptoms at baseline showed improvement in the YMRS in the first 2 weeks. While 7 of the 16 (44%) patients met the criterion for manic response and remission at last observation, 4 showed intervening periods of moderate to marked exacerbation. Levetiracetam was weight neutral.. Other pilot trials should explore possible areas of psychotropic action of levetiracetam prior to the conduct of more controlled clinical trials.

Topics: Adult; Ambulatory Care; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Levetiracetam; Longitudinal Studies; Male; Pilot Projects; Piracetam; Polyvinyls; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Pilot Projects; Piracetam

Levetiracetam is a novel antiepileptic drug with a broad spectrum of efficacy in epilepsy. We have tested the antimanic properties of the drug as an add-on to haloperidol in an open trial.. After giving informed written consent, 10 bipolar I acutely manic (DSM-IV) inpatients were investigated in an on-off-on study design. All patients were treated with 5 to 10 mg/day of haloperidol, depending on tolerability, throughout the investigation. Levetiracetam (up to 4000 mg/day) was added until day 14, then discontinued and reintroduced at day 21. The psychopathologic changes were assessed with the Young Mania Rating Scale (YMRS).. After a mean decrease of the YMRS scores from 29.6 to 17.2 during the first "on" phase, manic symptoms worsened during the "off" period (YMRS score 20.9) and ameliorated again during the second "on" phase, with a decrease of the mean YMRS score to 14.7 at the end of the study. The mean dose of levetiracetam was 3125 mg/day. At day 14, only 2 (20%) of 10 patients were responders (defined as a decrease in YMRS scores of 50%) compared with 7 (70%) of 10 responders at the end of the study at day 28.. The results from this open on-off-on add-on study suggest that levetiracetam exhibited additional antimanic effects. Controlled studies are clearly required.

Topics: Acute Disease; Adult; Anticonvulsants; Bipolar Disorder; Diagnostic and Statistical Manual of Mental Disorders; Drug Administration Schedule; Drug Tolerance; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Research Design

Topics: Antimanic Agents; Bipolar Disorder; Deep Brain Stimulation; Electroencephalography; Humans; Levetiracetam; Valproic Acid

Hyperactive intracellular calcium ion (Ca) signaling in peripheral cells has been a reliable finding in bipolar disorder. Some established mood stabilizing medications, such as lithium and carbamazepine, have been found to normalize elevated intracellular Ca concentrations ([Ca]i) in platelets and lymphocytes from bipolar disorder patients, and some medications the primary effect of which is to attenuate increased [Ca]i have been reported to have mood stabilizing properties.Hyperactive intracellular Ca signaling has also been implicated in epilepsy, and some anticonvulsants have calcium antagonist properties. This study demonstrated that levetiracetam, an anticonvulsant that has been shown to block N and P/Q-type calcium channels in animal studies does not alter elevated [Ca]i in blood platelets of patients with bipolar disorder. Review of published clinical trials revealed no controlled evidence of efficacy as a mood stabilizer.This study underscores the possibility that pharmacologic actions of a medication in animals and normal subjects may not necessarily predict its pharmacologic or clinical effects in actual patients. Effects of treatments on pathophysiology that is demonstrated in clinical subtypes may be more likely to predict effectiveness in those subtypes than choosing medications based on structural similarities to established treatments.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Calcium; Calcium Channel Blockers; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam

Topics: Acute Disease; Adolescent; Anticonvulsants; Bipolar Disorder; Dose-Response Relationship, Drug; Female; Humans; Levetiracetam; Piracetam; Psychiatric Status Rating Scales; Remission Induction; Treatment Outcome

Topics: Aged; Anticonvulsants; Antimanic Agents; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Pilot Projects; Piracetam; Psychiatric Status Rating Scales; Treatment Outcome

Bipolar patients with early-onset, comorbid substance abuse, rapid cycling, and mixed episodes are difficult to treat and frequently require rational polypharmacy. When polypharmacy is unsuccessful, the clinician must consider the off-label use of newer psychotropics. Levetiracetam is a novel anticonvulsant with antikindling, inhibitory, and neuroprotective properties that is effective in an animal model of mania. This case report describes a patient with treatment-resistant rapid cycling bipolar disorder who failed 15 psychotropics, individually or in various combinations (maximum of 6), but ultimately responded to levetiracetam monotherapy and remained without bipolar features during 1 year of maintenance treatment, excluding 1 week during which the patient was medicine noncompliant. Further, methylphenidate used to treat comorbid attention deficit disorder did not precipitate manic features. Levetiracetam should be further studied for its potential use in the treatment of bipolar disorders.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Female; Humans; Levetiracetam; MEDLINE; Piracetam; Review Literature as Topic; Treatment Outcome

Levetiracetam (LEV) is a novel anticonvulsant that is currently investigated in bipolar disorder. It may be useful in the treatment of refractory and complicated cases, in which conventional mood stabilizers are not effective. We report two cases of rapid cycling bipolar disorder in which the add-on of LEV to a conventional treatment regimen improved symptoms of depression, as well as those of mania/mixed mania, and disrupted the severe rapid cycling pattern.

Topics: Antidepressive Agents; Antimanic Agents; Bipolar Disorder; Drug Therapy, Combination; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Valproic Acid

Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations.. A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae.. In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Drug Overdose; Female; Half-Life; Humans; Levetiracetam; Neurologic Examination; Piracetam; Poisoning; Respiration, Artificial; Respiratory Insufficiency; Suicide, Attempted

Topics: Acute Disease; Adult; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Levetiracetam; Male; Piracetam; Psychiatric Status Rating Scales; Treatment Outcome