levetiracetam and Anxiety-Disorders

This report reviews behavioral adverse events occurring among adults receiving levetiracetam (LEV) or placebo who participated in short-term, placebo-controlled studies in epilepsy (1023), cognitive disorders (719), or anxiety disorders (1510) and epilepsy patients (1393) observed in long-term trials. Behavioral events (affective, psychotic, and suicidal symptoms) were significantly more common among epilepsy patients than cognition or anxiety patients treated with LEV for similar durations (P=0.022). Affective symptoms occurring at 1% or more often in epilepsy placebo-controlled trials included depression (3.8% LEV-2.1% placebo), nervousness (3.8%-1.8%), hostility (2.3%-0.9%), anxiety (1.8%-1.1%), and emotional lability (1.7%-0.2%). Patients with cognitive and anxiety disorders had lower incidences of these symptoms. The incidence of behavioral events in LEV-treated epilepsy patients was lower than rates reported for some other antiepileptic drugs. These data support the hypothesis that some feature related to epilepsy is the cause of many behavioral events rather than the addition of a specific antiepileptic drug.

Topics: Anticonvulsants; Anxiety Disorders; Cognition Disorders; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Epilepsy; Follow-Up Studies; Humans; Levetiracetam; Mood Disorders; Outcome Assessment, Health Care; Periodicity; Piracetam; Psychotic Disorders; Randomized Controlled Trials as Topic; Suicide, Attempted

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

Interictal depression is common in patients with epilepsy and it significantly impacts quality of life. Some studies indicate that levetiracetam (LEV) may have mood stabilizing properties.. Twenty-five adults with uncontrolled partial seizures and concomitant depressive symptoms were treated with LEV. Patients were evaluated for depression and anxiety with several psychometric measures, including: Montgomery and Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Zung Self-rating Scale for Depression (Z-SDS), Hamilton Anxiety Rating Scale (HARS), Zung Self-rating Scale for Anxiety (Z-SAS).. Evaluations after 5 weeks and after 3 months of LEV treatment demonstrated significant improvement in depression and anxiety.. This uncontrolled study suggests that treatment with LEV may also improve depression and anxiety in patients with partial seizures. However, the sample of patients is limited and the possibility of a placebo effect cannot be excluded. These findings must be considered preliminary and should be replicated under placebo-controlled conditions.

Topics: Adult; Age Factors; Anticonvulsants; Anxiety Disorders; Depressive Disorder; Dizziness; Epilepsies, Partial; Female; Humans; Levetiracetam; Male; Piracetam; Placebo Effect; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD).. We used proton magnetic resonance spectroscopy (pMRS) to examine whole brain and regional GABA, glutamate and glutamine in patients (N=10) with SAD at baseline compared to a matched group of healthy controls (HC), and changes following 8 weeks of pharmacotherapy with levetiracetam.. For SAD subjects, there were significantly higher whole brain levels of glutamate and glutamine, though no significant differences in GABA. In the thalamus, glutamine was higher and GABA lower for SAD subjects. There was a significant reduction in thalamic glutamine with levetiracetam treatment.. Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam.

Topics: Adolescent; Adult; Aged; Anxiety Disorders; Female; gamma-Aminobutyric Acid; Glutamic Acid; Glutamine; Humans; Levetiracetam; Magnetic Resonance Spectroscopy; Male; Middle Aged; Nootropic Agents; Piracetam

To gather real-world evidence on antiseizure medications (ASMs) treatment patterns and related outcomes in patients with drug-resistant focal epilepsy.. Medical insurance claims from the start of 2014 till the end of 2019 were used. Patient selection criteria included International Classification of Diseases (ICD) codes followed by documented ASM use. Baseline patient demographics along with ASM and rescue medication use patterns and related patient outcome were documented for first (index) ASM regimen. Patients who failed the first regimen and then failed the second regimen were considered drug resistant. Multivariate analyses were performed to identify risks and other characteristics for positive or negative treatment outcomes.. Study cohort consisted of 46 474 patients with a mean age of 47.23 (SD: 16.94). Levetiracetam was the most first-encountered ASM (37.94%). At baseline, 87.14% were treated with ASMs prior to having study-confirmed diagnoses. Mental comorbidities were present in 37.86% of patients. After first-year ASM treatment, 34.61% of patients persisted on their index regimen and 5.91% were seizure-free. Patients failing first ASM regimen numbered 12 868 (27.69%). Drug-resistant patients who failed first and then second ASM regimens numbered 6335 (49.23%). Percentages of patients who had successful second treatment and seizure-free were 21.32 and 3.65, respectively. Initiating patients on lamotrigine or carbamazepine (relative to levetiracetam), baseline use of index ASM, rescue medications, and older age or male gender all lowered the risk for treatment failure. Having higher comorbidity, comorbid mental illness, headache, or neoplasty increased such a risk. Baseline use of index ASM, depressive episode, or anxiety disorder all entailed higher risk of failing second ASM treatment.. Overall, reported findings indicated that patient history at baseline and the early selection of an ASM all influenced treatment outcomes. Findings pointed to the complex nature of ASM treatment in drug-resistant focal epilepsy patients calling for additional research to identify the optimal treatment to achieve beneficial patient outcomes.

Topics: Anxiety Disorders; Drug Resistant Epilepsy; Epilepsies, Partial; Humans; Levetiracetam; Male; Middle Aged; Treatment Failure; Treatment Outcome

Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear.. To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy.. A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018.. Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared.. Antiepileptic drug treatment pattern according to seizure type and comorbidities.. Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]).. Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Topics: Adolescent; Adult; Anticonvulsants; Anxiety Disorders; Comorbidity; Dissociative Disorders; Epilepsies, Partial; Epilepsy, Generalized; Female; Headache Disorders; Humans; Lamotrigine; Levetiracetam; Mental Disorders; Migraine Disorders; Mood Disorders; Oxcarbazepine; Phenytoin; Retrospective Studies; Risk; Teratogens; Topiramate; Valproic Acid; Young Adult

A common side effect of levetiracetam is the onset of neuropsychiatric symptoms such as mood changes including depression, anxiety, agitation, and sometimes psychosis. We performed a retrospective analysis to examine the effect of sleep pattern and chronotype on individual susceptibility to levetiracetam-induced mood changes. We reviewed records of 110 adults with epilepsy presenting to our clinic during a 3-month period, and categorized them into those currently on levetiracetam, and those no longer taking it because of mood-related adverse effects. Patients were administered Morningness-Eveningness Questionnaire (MEQ), Beck's Depression Inventory-II, and Neurological Disorders Depression Inventory in Epilepsy. Using various statistical methods, we analyzed the comparison of these 3 different scales amongst one another and between those subjects who tolerated levetiracetam and those who did not. Of 110 patients, 74 (67%) tolerated levetiracetam and 36 (33%) did not tolerate it because of mood changes with chronotype being a significant determining factor. Of those who tolerated the drug, 62% were intermediate chronotypes and 20.3% and 17.6% were morning and evening chronotypes, respectively. For those intolerant, 86.1% were morning chronotypes, 13.9% were intermediate chronotypes, and none were evening chronotypes (p<0.001). Thirty-two percent of morning chronotypes, 100% of evening chronotypes, and 90.2% of intermediate chronotypes were tolerant of levetiracetam (p<0.001). Chronotype significantly affected toleration of levetiracetam. Chronotype, but not depression, was a significant factor in determining tolerability of mood-altering side effects of levetiracetam, via statistically significant trend for an increasing ability to tolerate levetiracetam as chronotype would shift from morning to intermediate to evening. Additional research may help establish if this is related to possible underreporting of poor mood with evening chronotypes, and morning chronotypes having more stringent sleep schedules, genetic factors, or other reasons.

Topics: Adult; Analysis of Variance; Anticonvulsants; Anxiety Disorders; Circadian Rhythm; Depressive Disorder; Epilepsy; Female; Humans; Incidence; Levetiracetam; Male; Middle Aged; Mood Disorders; Piracetam; Retrospective Studies; Sleep; Surveys and Questionnaires; Young Adult

Anxiety disorders are the most prevalent psychiatric disorders as a group, and despite the effectiveness of currently available treatments for anxiety, many patients (40%-65%) remain symptomatic after initial intervention. Thus, there is a significant need for efficacious pharmacologic agents that are safe and well tolerated and lead patients to remission of symptoms. We present a retrospective analysis that assessed the efficacy and tolerability of adjunctive levetiracetam, a novel anticonvulsant agent, in the treatment of refractory anxiety.. Forty patients with DSM-IV anxiety disorders, who were deemed partial responders or nonresponders to anxiolytic therapy, received adjunctive levetiracetam in a naturalistic fashion during the time period from January 2004 through December 2004. We conducted a retrospective chart review. The primary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) scale and the Clinical Global Impressions-Improvement (CGI-I) scale. Mean change from baseline to endpoint was assessed using 2-tailed paired t tests.. Levetiracetam at a mean +/- SD dose of 1969 +/- 819 mg/day for a mean +/- SD time period of 9.3 +/- 5.1 weeks was generally well tolerated. Patients were markedly ill with a mean +/- SD baseline CGI-S score of 6.2 +/- 0.6. Patients improved significantly, with an endpoint CGI-S score of 4.2 +/- 1.8 (p < .001) and CGI-I score of 2.6 +/- 1.2. Adverse events were generally mild, and only 4 patients discontinued levetiracetam because of side effects.. These preliminary data suggest that levetiracetam may be an effective adjunctive treatment for patients with anxiety disorders who remain symptomatic despite initial anxiolytic therapy.

Topics: Adult; Aged; Anticonvulsants; Anxiety Disorders; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Treatment Outcome

The purpose of this analysis was to compare treatment-emergent adverse events (TEAE) related to use of levetiracetam (LEV) reported by young and elderly patients with anxiety and cognitive disorders, and young epilepsy patients. The LEV database includes reports of TEAE from trials of patients with diagnoses of a cognitive disorder (N=719), an anxiety disorder (N=1510), or localization-related epilepsy (N=1023) who participated in clinical trials lasting up to 16 weeks. Patients were grouped as young (<65 years) or elderly (> or = 65 years). The most common TEAE occurring most frequently in the LEV-treated groups were abdominal pain, asthenia, headache, anorexia, weight loss, dizziness, insomnia, somnolence, and tremor. The only significant differences in TEAE were seen between young and elderly groups with anxiety disorders (>3% higher for LEV than for placebo-treated patients) in headache (5.2% elderly, -0.9% young, P=0.041), and tremor (5.2 and -0.5%, respectively, P=0.022) and between young anxiety patients and young epilepsy patients for somnolence (-0.7 and 5.4%, respectively, P=0.036). For the other TEAEs there was no evidence for consistent differences between young and elderly patients and between patients with different CNS disorders. Overall, LEV was well tolerated by all patient groups. The favorable adverse event profile suggests that LEV might be suitable for use by elderly patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Anticonvulsants; Anxiety Disorders; Central Nervous System Diseases; Cognition Disorders; Epilepsy; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam