LAUSR

To the Editor: Levetiracetam is a new antiepileptic that is effective as an adjunctive therapy for refractory partial-onset seizures, primary generalized tonic–clonic seizures, myoclonic seizures of juvenile myoclonic epilepsy,1 and the seizure prophylaxis after brain surgery.2 Several previous studies have reported psychotic symptoms, induced by levetiracetam in patients with underlying epilepsy,3–6 but psychotic symptoms in the prophylactic usage of levetiracetam after brain surgery has not, as yet, been reported. Here, we have reported on a patient who has suffered from visual and auditory hallucinations related to the levetiracetam prophylactic therapy after having brain surgery. A 52-year-old female patient, without any psychiatric history or a history of epilepsy, was admitted to the neurosurgical department for a ruptured cerebral aneurysm of the anterior communicating artery. The brain computed tomography scan showed the diffused subarachnoid hemorrhage with hyperdense blood accumulating in the extracerebral cerebrospinal fluid space. She received external ventricular drainage with an intracranial pressure monitor implantation and left pterional approach by the clipping of the anterior communicating artery aneurysm. For the prevention of a seizure attack, levetiracetam 500 mg per day was administered intravenously for 12 days and then shifted to the oral form twice daily after being prescribed for the prevention of epilepsy. After being given levetiracetam for 24 days, she began experiencing visual and auditory hallucinations 4–5 times a day. During the treatment time after the surgery, the patient’s consciousness was clear. After the hallucinations occurred, laboratory investigations, including a complete blood count, serum electrolyte levels, renal and liver function tests, and urine analysis, were all normal. A brain computed tomography scan at that time also revealed a nearly total resolution of a diffused subarachnoid hemorrhage. The electroencephalography did not show any unusual activity. Hallucinations were provisionally attributed to levetiracetam, and the antiepileptic was replaced by sodium valproate 1200 mg orally daily. Then, the patient recovered from her hallucinations within 48 hours of medication adjustment. Complete recovery from psychotic symptoms after stopping levetiracetam supports this possible adverse drug reaction, from the Naranjo’s algorithm.7 The causality was not certain as there was no rechallenge and the drug level was also unknown as required for the Naranjo’s algorithm. For the patient’s benefit, we did not use a rechallenge, but the temporal sequence of events and the negative diagnostic workup revealed the possibility of levetiracetam-induced psychotic symptoms. Although the mechanisms underlying the levetiracetam-induced psychotic symptoms remain unclear, the fact that levetiracetam partially blocks the N-type high-voltage activated calcium channels1 might well contribute to this adverse event because the animal model indicated that the voltage-sensitive calcium channel blockers can induce a massive increase of basal dopamine extracellular levels.8 To the best of our knowledge, this might be the first case reported on the topic of levetiracetam-related psychotic symptoms after its usage for the prophylactic treatment in a patient after brain surgery without a previous history of epilepsy. The findings about the specific potential side effect also acts as a reminder for the clinicians to monitor the psychotic symptoms related to the prophylactic levetiracetam therapy for patients after brain surgery and provide the clinical strategy accordingly.