Depression levetiracetam

Levetiracetam Unknown Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 000-3000 mg/day. Start at 1 000 mg/day and titrate upward as indicated by response Half-life Not established 6-8 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding less than 10% Primary elimination route 70% renal 30% hepatic Somnolence, dizziness Depression... 

Levetiracetam Action on synaptic protein SV2A Well absorbed orally not bound to plasma proteins metabolized to 3 inactive metabolites ty2 6-11 h Generalized tonic-clonic seizures, partial seizures, generalized seizures Toxicity Nervousness, dizziness, depression, seizures Interactions Phenobarbital, phenytoin, carbamazepine, primidone... 

A 38-year-old woman took 60 tablets of levetiracetam 500 mg. She vomited 4 hours later, and 2 hours after that was obtunded with respiratory depression. Her levetiracetam serum concentration was 400 pg/ml at 6 hours, 72 pg/ml at 18 hours, and 60 pg/ml at 20.5 hours (target serum concentration 10-37 pg/ml). The half-life was 5.1 hours, similar to the usually reported half-life. She was extubated the next day and recovered without sequelae. 

Comparative studies Levetiracetam versus phenytoin Levetiracetam monotherapy has been compared with phenytoin for postoperative control of glioma-related seizures in a randomized pilot study [181 ]. Over 13 months, 29 patients were randomized in a 2 1 ratio to start levetiracetam within 24 hours of surgery or to continue phenytoin therapy. Similar percentages of patients were seizure-free after 6 months of treatment. Reported adverse effects at 6 months were dizziness (0% levetiracetam, 14% phenytoin), difficulty with coordination (0% versus 29%), depression (7% versus 14%), lack of energy or strength (20% versus 43%), insomnia (40% versus 43%), and mood instability (7% versus 0%). No adverse effect resulted in hospitalization or withdrawal from the study. 

Depression has been described in both elderly epileptic patients [191 ] and a child with epilepsy [192 ], probably caused by levetiracetam. 

A 73-year-old black man with stage 4 kidney disease was given levetiracetam 500 mg bd for treatment of partial seizures. After 5 months he developed new-onset depression, with low mood, weight loss, and fatigue. Levetiracetam was withdrawn and 4 weeks later the depressive symptoms had nearly completely resolved. 

Van de Griend JP, Linnebur SA, Bainbridge JL. Probable levetiracetam-associated depression in the elderly two case reports. Am J Geriatr Pharmacother 2009 7(5) 281-4. 

Observational studies A phase 111 study evaluated the safety and efficacy of levetiracetam in 217 children and adults with primary generalized seizures. The most common adverse effects reported by >10% participants were headache and nasopharyngitis. The most frequent treatment-associated adverse effects were headache (4.6%), dizziness and depression (both 4.1%). Serious adverse effects related to treatment with levetiracetam 4.6% of patients experienced convulsion, atrial fibrillation, epilepsy, depression, psychosis, schizophrenia, suicidal ideation, erythematous rash, and status epilepticus. One patient each discontinued due to the following adverse effects arrhythmia, convulsions, tremor, aggression, depression, psychosis, and exanthem. One patient with worsening of comorbid schizophrenia committed suicide it had been 43 days since he had last taken levetiracetam at the time [87 -]. 

A patient without any history of psychiatric disorder was reported to develop acute onset major depression with a near fatal suicide attempt after starting levetiracetam. The authors suggest that psychiatric evaluation and assessment of risk factors for suicidal behaviors may be indicated in treating patients with epilepsy with levetiracetam [95 ]. 

Kaufman KR, Bisen V, Zimmerman A, Tobia A, Mani R, Wong S. Apparent dose-dependent levetiracetam-induced de novo major depression with suicidal behavior. Epilepsy Behav Case Reports 2013 1 110-2. 

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