Levetiracetam for Managing Neurologic and Psychiatric Disorders

Muhammad U. Farooq; Archit Bhatt; Arshad Majid; Rishi Gupta; Atul Khasnis; Mounzer Y. Kassab


Am J Health Syst Pharm. 2009;66(6):541-561. 

In This Article

Adverse Effects

Levetiracetam can cause a wide spectrum of behavioral adverse effects. These can occur in up to 16% of treated patients.[100] Patients on levetiracetam therapy can develop hallucinations, apathy, emotional lability, agitation, irritability, and hostility. These adverse effects have been reported in some cases with underlying anxiety and depression that were exacerbated by levetiracetam. These behavioral adverse effects, or so-called "levetiracetam psychosis," are more common in children and in patients with a history of behavioral problems. These psychiatric problems can be the primary reason for discontinuation of the medication.[100,101,102,103,104]

Kossoff et al.[101] described four pediatric cases of epilepsy (ages ranged from 5 to 17 years) with levetiracetam psychosis. These children developed delusions and auditory or visual hallucinations within two days to three months of levetiracetam therapy. The initial dosage of levetiracetam used ranged from 15 to 25 mg/kg/day with a plan to increase the dosage in two weeks. There was no history of psychosis in these children. However, all of the children had a history of cognitive deficits, and some of them also had mild behavioral issues. In all of these children, psychosis was reversible within days of termination of levetiracetam therapy. Slow initiation and increase in the levetiracetam dosage (10 mg/kg/day and increasing over a four-week period to 20 mg/kg/ day) are recommended to avoid these psychiatric complications.[101]

Mula et al.[105] conducted a study to evaluate the prevalence of psychiatric adverse events in 517 patients taking different doses of levetiracetam for different seizure disorders, including cryptogenic partial epilepsy, idiopathic generalized epilepsy, West syndrome, and Lennox-Gastaut syndrome. The mean ± S.D. age of patients with epilepsy with psychiatric adverse effects was 34.6 ± 12.5 years and with epilepsy without psychiatric adverse effects was 36.5 ± 11.5 years. The researchers classified these adverse effects, assessed the clinical relevance and outcomes, and defined the relationship to seizure pattern and frequency. Fifty-three patients (10%) developed psychiatric adverse events including affective disorders (2.5%), psychosis (1.2%), aggressive behavior (3.5%), emotional lability (2.3%), suicidal ideation (0.7%), and other behavioral abnormalities (0.6%) such as agitation, anger, hostile behavior, and personality changes. In contrast to the slow levetiracetam titration as recommended by Kossoff et al.,[101] this study highlighted that the levetiracetam-associated psychiatric adverse effects were not related to the starting dose or titration of levetiracetam. There might be some factors other than initial dose and titration of levetiracetam that are responsible for levetiracetam-associated psychiatric adverse effects.[105] Most of these behavioral problems associated with levetiracetam therapy resolved with discontinuation of medication in clinical trials and were not associated with any long-term disability.

The adverse events that result from oral and i.v. levetiracetam use are the same. In clinical trials, the incidence of adverse effects leading to dosage reduction or discontinuation of drug was 15%. It was similar to the incidence of these adverse effects with placebo (11.6%). The most common adverse effects of levetiracetam included somnolence (15%), asthenia (15%), headache (14%), infection (13%), and dizziness (9%).[106] Some patients experience various behavior abnormalities such as depression (4%) and nervousness (4%). Other adverse effects include agitation, anger, anxiety, emotional lability, hostility, psychosis and suicidal ideation.[106]


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