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Nonepileptic Hallucinations in Use of Levetiracetam

TO THE EDITOR: Levetiracetam (LEV), a new antiepileptic drug with a novel mechanism of action, shows safe and proven efficacy in partial epilepsy. LEV has become widely used as add-on therapy in patients with epileptic disorders. It is mainly prescribed in outpatient epilepsy or neurology clinics. However, its favorable pharmacokinetic profile, lack of known pharmacologic interactions, good tolerability, and possibility of fast titration suggest that it may be a very useful drug in hospitalized patients, as well.¹ Several neuropsychological symptoms may develop during antiepileptic drug treatment; however, there are few reports in the literature regarding the association of LEV with psychosis.^2–4 To our knowledge, this is the first report of levetiracetam-induced hallucinations in a subject without underlying neurological disease.

Case Report

"Ms. A" is a 28-year old healthy woman with no psychiatric history, diagnosed with possible complex partial seizures in 2006 and treated with Keppra 500 mg twice daily for 2 months. Because of its lack of efficacy, she was hospitalized for 24-hour video and EEG monitoring for questionable seizures, versus panic attacks. The Keppra dosage had been increased progressively over 2 weeks, to 1,500 mg AM and 1,000 mg HS. After the dose increase, she described experiencing visual and tactile hallucinations of a large insect resembling a beetle resting on her forehead. During 24-hour monitoring, she reported the hallucinations. There were independent episodes of anxiety associated with strong heartbeats lasting 2–3 minutes without any alteration of consciousness, confusion, or behavioral changes. None of the episodes were associated with any EEG or ECG change, and the EEG remained normal throughout the 5-day testing. Physical examination was unremarkable, and laboratory results, including urinalysis, CBC, liver function test, and kidney function, were within normal limits. Urine drug screen was negative, and she denied any alcohol use. The brain MRI was normal.

Keppra was discontinued, and the hallucinations resolved shortly afterward, with no need for antipsychotics. The patient was diagnosed as having panic attacks. She was started on a selective serotonin reuptake inhibitor (SSRI), but then opted for no-treatment and did well.

Discussion

We think it can be safely assumed that our patient had levetiracetam-induced visual and tactile hallucinations. She also suffered from panic attacks that preceded the start of levetiracetam treatment; these were incorrectly diagnosed as partial seizures.

With the rapid release of new antiepileptic medications onto the market, drug information regarding side effects and benefits are often limited because of lack of experience with a sufficient number of patients. Controlled clinical trials have reported a wide margin of tolerability, with infrequent and mild adverse events for levetiracetam.⁵ During long-term treatment, behavioral disturbance was noted in 2% of patients. Clinical studies have indicated a higher prevalence of psychiatric adverse events, ranging between 13.5% and 16%,⁶ and prevalence rates of levetiracetam-induced psychosis range from <1% to 1.4%.⁴ Data about psychosis are available only as case reports.^2–4 Risk factors for the development of psychosis are previous history of status epilepticus, previous psychiatric history, add-on therapy, and rapid titration when there is an underlying neurological disease.⁶

The lack of EEG change during hallucinations in our patient makes epileptic seizures a highly unlikely cause.⁷ Further evidence against the hallucinations being caused by seizures is the fact that the symptoms resolved as the drug was discontinued.

This observation is important because it demonstrates that hallucinations can have multiple causes, even when there is an otherwise normal mental status. Psychotic symptoms arising during initiation or titration of pharmacotherapy in patients should not be automatically attributed to a neurological disorder, and abnormal perceptual experiences should be monitored in future studies. Until then, clinicians need to be aware of this possible complication associated with levetiracetam.

REFERENCES

1. Falip M, Carreno M, Amaro S, et al: Use of levetiracetam in hospitalized patients. Epilepsia 2006; 47:2186–2218[CrossRef][Medline]
2. Kossoff EH, Bergey GK, Freeman JM, et al: Levetiracetam psychosis in children with epilepsy. Epilepsia 2001; 12:1611–1613
3. Youroukos S, Lazopoulou D, Michelakou D, et al: Acute psychosis associated with levetiracetam. Epileptic Disorders 2003; 2:117–119
4. Bayerlein K, Frieling H, Beyer B, et al: Drug-induced psychosis after long-term treatment with levetiracetam. Can J Psychiatry 2004; 49:868[Medline]
5. Privitera M: Efficacy of levetiracetam: a review of three pivotal clinical trials. Epilepsia 2001; 42:31–35
6. Mula M, Trimble MR, Yuen A, et al: Psychiatric adverse events during levetiracetam therapy. Neurology 2003; 5:704–706
7. Manford M, Andermann F: Complex visual hallucinations: clinical and neurobiological insights. Brain 1998; 121:1819–1840[Abstract/Free Full Text]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Evcimen, H. Articles by Jenssen, S. Search for Related Content PubMed Citation Articles by Evcimen, H. Articles by Jenssen, S. Anticonvulsants

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