levetiracetam and Depressive-Disorder

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

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

Corticosteroid excess is associated with impairment in declarative memory and hippocampal changes. In animals, phenytoin blocks the effects of stress on memory and hippocampal histology. Levetiracetam also shows neuroprotective properties in some animal models. This report examines whether levetiracetam prevents mood or cognitive changes secondary to prescription corticosteroids.. Thirty outpatients given systemic corticosteroid therapy for asthma were randomized to either levetiracetam (1500 mg/day) or placebo given concurrently with the corticosteroids. Mood was assessed with the Hamilton rating scale for depression (HRSD), Young mania rating scale (YMRS) and activation (ACT) subscale of the internal state scale, declarative memory with the Rey auditory verbal learning test (RAVLT), and attention and executive functioning with the Stroop color and word test at baseline and after approximately 7 days of corticosteroid plus levetiracetam or placebo therapy.. Levetiracetam and placebo groups showed significant improvement from baseline to exit on RAVLT total words recalled with a non-significant change on other outcomes. No significant between-group differences were found. Initial prednisone dose showed a significant correlation with change in some cognitive domains.. Levetiracetam was well tolerated when combined with prednisone. Significant between-group differences in mood and cognition were not found.

Topics: Adolescent; Adult; Affect; Aged; Anti-Inflammatory Agents; Antidepressive Agents; Asthma; Cognition; Depressive Disorder; Double-Blind Method; Drug Administration Schedule; Female; Humans; Levetiracetam; Male; Memory; Middle Aged; Neuropsychological Tests; Piracetam; Prednisone; Surveys and Questionnaires

Topics: Adolescent; Anticonvulsants; Antidepressive Agents, Second-Generation; Bupropion; Depressive Disorder; Drug Overdose; Electrocardiography; Female; Follow-Up Studies; Humans; Levetiracetam; Myoclonus; Suicide, Attempted; Tachycardia

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

Epilepsy is one of the major neurological disorders frequently associated with psychiatric disorders such as depression. The predisposition of tryptophan metabolism towards kynurenine pathway has been reported as one of the plausible reasons for association of depression in epilepsy. Hence, this study was envisaged to evaluate the dose dependent inhibition of indoleamine 2,3-dioxygenase (IDO) enzyme employing quercetin (screened employing in vitro method) with levetiracetam for combined management of epilepsy and comorbid depression. Kindling was induced in male swiss albino mice by administration of pentylenetetrazole subconvulsive doses (35 mg/kg, i.p.) at an interval of 48 ± 2 h. Kindled animals were treated with vehicle, levetiracetam (40 mg/kg/day i.p.) levetiracetam in combination with different doses of quercetin (10 mg/kg; 20 mg/kg; 40 mg/kg)/day/p.o. for 15 days. Except naïve, all the groups were challenged with pentylenetetrazole (35 mg/kg i.p.) on day 5, 10, and 15 to evaluate the seizure severity score. Depression was evaluated in all experimental groups using the tail suspension and sucrose preference test on days 1, 5, 10 and 15, 2 h after pentylenetetrazole challenge. Results suggested that vehicle treated kindled animals were significantly associated with depression. Chronic levetiracetam treatment significantly reduced seizure severity score, but further worsened the associated depression. Quercetin supplementation with levetiracetam dose dependently ameliorated depression associated with epilepsy. Neurochemical and biochemical findings also supported the behavioural findings of the study. Thus, our results suggested that supplementation of quercetin with levetiracetam could be explored further for combined treatment of epilepsy and comorbid depression.

Topics: Animals; Anticonvulsants; Behavior, Animal; Brain; Combined Modality Therapy; Convulsants; Depression; Depressive Disorder; Disease Models, Animal; Epilepsy; Levetiracetam; Male; Mice; Pentylenetetrazole; Piracetam; Quercetin