Neurol Sci (2012) 33:1161–1163 DOI 10.1007/s10072-011-0869-9
CASE REPORT
Vulnerability of an epileptic case to psychosis: Sodium valproate with lamotrigine, forced normalization, postictal psychosis or all? A. B. Turan • M. Seferoglu • O. Taskapilioglu I. Bora
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Received: 27 May 2011 / Accepted: 18 November 2011 / Published online: 1 December 2011 Ó Springer-Verlag 2011
Abstract Patients with epilepsy can be considered to be at high risk for developing psychotic disorders. Furthermore, there is association between seizure freedom or the disappearance of the interictal epileptiform events from the EEG record and the occurrence of psychotic symptoms. Also, several newer antiepileptic drugs have been reported to induce psychotic symptoms. We present a patient with epilepsy who developed psychotic symptoms under the treatment of valproic acid (VPA) and lamotrigine (LTG) combination. The mechanism underlying the association between LTG, seizure control and development of psychosis are discussed in the light of the literature.
AEDs may be an alternative mechanism explaining psychosis [2]. We present a patient with epilepsy who experienced psychotic symptoms after receiving valproic acid (VPA) and lamotrigine (LTG) in combination. The contribution of VPA-LTG combination, forced normalization, postictal psychosis or all to the development of psychotic symptoms will be discussed based on our experience with this patient and a few similar case reports in the literature.
Keywords Epilepsy Psychosis Lamotrigine Valproic acid Forced normalization
A 30-year-old male, without history of psychosis, was diagnosed with idiopathic generalized epilepsy at the age of 8. He was being treated on outpatient basis. Upon increased frequency of seizures, he was admitted to our video-EEG monitorization unit where nonconvulsive status epilepticus (SE) was diagnosed (Fig. 1). During SE, he was treated with 40 mg/kg/day VPA intravenously which led to the disappearance of the interictal epileptiform events from the EEG record with a decreased frequency of absence seizures. Then he was started on VPA 1,000 mg/day orally. On day 7 of oral VPA treatment, 25 mg/alternate day LTG was added. After the first dose of LTG, he developed a cold, detached manner with incoherent speech. After the second dose of LTG, he developed psychotic symptoms (paranoid thoughts, agitation, sleep disturbances, confusion) and he was consulted by a psychiatrist. His vital signs and serum electrolytes level were normal. The symptoms of the patient did not meet the DSM-IV criteria for delirium and manic episode and he was diagnosed with ‘psychotic disorder due to a general medical condition’. Oral risperidone 3 mg/day was started. During the VPA-LTG combination, the frequency of his absence seizures decreased.
Introduction Epileptic patients can be considered to be at high risk for developing psychotic disorders [1]. Psychotic symptoms often occur after clusters of seizures and are associated with seizure frequency and severity. Additionally, there is association between seizure freedom or the disappearance of the interictal epileptiform events from the electroencephalography (EEG) record and the occurrence of psychotic symptoms [2]. Psychosis as an adverse event of antiepileptic drug (AED) therapy is generally rare, but several newer AEDs have been reported to induce psychotic symptoms [3]. Forced normalization caused by A. B. Turan (&) M. Seferoglu O. Taskapilioglu I. Bora Department of Neurology, Uludag University Medical Faculty, 16059 Gorukle/Bursa, Turkey e-mail:
[email protected]
Case report
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Fig. 1 EEG, recorded when nonconvulsive status epilepticus was diagnosed
On day 5 of VPA-LTG combination treatment, the severity of psychotic behaviors so increased that he had to be transferred to a psychiatry ward. His antiepileptic treatment was administered as 1,500 mg/day VPA and 25 mg/day LTG. One week after his discharge from neurology ward, LTG dosage was increased to 50 mg/day. After his condition was stabilized, he began to be followed as an outpatient. In view of the fact that the seizures decreased in frequency but were still continuing with LTG-VPA combination, LTG was switched to levatiracetam (LEV) and then zonisamide (ZNS) was administered. Now his seizures are under control with the treatment of 1,500 mg/day VPA, 2,500 mg/day LEV and 300 mg/day ZNS. Although the psychotic symptoms have decreased, inconvenient behaviours, like pointless laughing, still continue.
Discussion We present a patient with epilepsy who developed psychotic symptoms under the treatment of valproic acid (VPA) and lamotrigine (LTG) combination. There are only a few case reports of psychosis treated with LTG [3]. LTG is a broadspectrum AED which may work synergistically when combined with VPA to provide superior seizure control in patients with absence seizures, complex partial seizures, and myoclonic epilepsy. In the study of Brodie et al. [4] LTGVPA combination provided a sustained improvement in seizure frequency in two-thirds of the patients with refractory epilepsy. Brandt et al. [5] described six patients who developed psychotic episodes under treatment with LTG and it is remarkable that two-thirds of these patients had LTG-VPA combination. On the basis of these studies, the onset of psychotic symptoms under treatment with LTG can be associated with an increase in LTG serum levels as a result of either increments in LTG itself, or addition of VPA. A potent combination treatment like LTG and VPA may also cause forced normalization which leads to psychoses.
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Postictal psychosis (PIP) is estimated to account for 25% of cases of psychosis associated with epilepsy. According to the diagnostic criteria for PIP defined by Logsdail and Toone, the beginning of confusion or psychosis has to be within 1 week of the return of apparently normal mental function since last seizure and also there has to be no evidence of drug toxicity [6]. PIP seems to be unlikely in this case because he didn’t meet the Logsdail criteria. The psychotic symptoms of the patient appeared while seizures persisted but decreased in frequency; therefore, alternating psychosis is still likely because it occurred when seizures ceased or were reduced significantly in frequency, often after a change in dose or the introduction of a new AED. But this is very rare and only 3 cases of alternating psychosis were reported in 697 epileptic patients by Schmitz and Wolf [7]. Van der Feltz-Cornelis et al. reported the prevalence of psychotic syndromes in epilepsy as 5.4% and found that the risk of developing psychosis is eighth fold in epilepsy compared to other chronic medical disorders [8]. Their hypothesis was that psychosis in epilepsy should be attributed rather to brain pathology. Our patient had the diagnosis of epilepsy for 22 years, during which such brain pathology could develop. Landolt coined the term forced normalization in his original paper and defined it as follows: ‘‘Forced normalization is the phenomenon characterized by the fact that, with the occurrence of psychotic states, the EEG becomes more normal or entirely normal as compared with previous and subsequent EEG findings’’ [2]. The EEG of our patient, repeated during psychosis, showed the disappearance of the interictal epileptiform events, suggestive of forced normalization. Of course we cannot exclude the possibility of a chance association between psychotic symptoms, LTG and forced normalization. In conclusion, the causes of psychosis in patients with epilepsy are hard-to-solve. We aimed to show that longterm prospective observational studies are needed to go into these unsolvable issues concerning the relationship between AEDs, forced normalization and psychosis.
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Neurol Sci (2012) 33:1161–1163 4. Brodie MJ, Yuen AW (1997) Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group. Epilepsy Res 26(3):423–432 5. Brandt C, Fueratsch N, Boehme V, Kramme C, Pieridou M, Villagran A, Woermann F, Pohlmann-Eden B (2007) Development of psychosis in patients with epilepsy treated with lamotrigine: report of six cases and review of the literature. Epilepsy Behav 11(1):133–139 6. Logsdail SJ, Toone BK (1988) Post-ictal psychoses. A clinical and phenomenological description. Br J Psychiatry 152:246–252
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