10:249â266. 3. Kulaksizoglu IB, Polat A: Quetiapine for mania with Wilson's disease. Psychoso- matics 2003; 44:438â439. Oxcarbazepine-Induced. Leukopenia.
LETTERS MRI did not reveal any abnormality. A slit lamp examination done by the ophthalmologist revealed bilateral Kayser-Flescher rings, and she was started on D-penicillamine, 750 mg/day. Since there was a progressive deterioration in her liver function, a liver transplant was advised by the gastroenterologist. Due to the pending investigations of the patient, the liver transplant was planned at a later date and her mother gave consent for partial liver donation. During this period, she developed insomnia, increased talkativeness and increased activity. She had no past or family history of psychiatric illness. The patient was transferred to psychiatry for management of these behavioral problems. Her mental status examination revealed overfamiliarity, distractibility, euphoric affect, increased psychomotor activity, and delusions of grandiosity with poor insight and judgment. She was started on a regimen of tablet haloperidol, 10 mg per day, in divided doses along with tablet promethazine, 15 mg, in divided doses. The dose of haloperidol was increased to 20 mg in divided doses after which she had significant extrapyramidal symptoms. Therefore the dosage was decreased to 10 mg per day; on reevaluation after 1 week her symptoms had decreased considerably. She was discharged and prescribed haloperidol, 7.5 mg per day, in divided doses and advised to have close follow-up. The patient is well maintained on a regimen of haloperidol, 7.5 mg/day on follow-up. Mood stabilizers like sodium valproate and carbamazepine were not started because of poor hepatic function and because elevated fasting blood glucose levels made atypicals a poor choice in this woman. Considering the possibility of renal tubular acidosis in Wilson’s disease and a history of polyuria, treatment
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with lithium carbonate was also withheld.1 Patients with Wilson’s disease are exquisitely sensitive to extrapyramidal side effects, and the dose titration should be gradual if typical antipsychotics are used, and they should be started at a lower dose.2 There are no specific guidelines regarding the treatment of neuropsychiatric manifestations in Wilson’s disease. Medications for psychosis and mania that have been used include quetiapine, clozapine and haloperidol, as well as ECT.1,3 There is a paucity of literature available regarding the treatment options in psychiatrically ill patients with Wilson’s disease. Multisystem involvement in Wilson’s disease can make the traditional medications difficult to use in these patients, and treatment regimens may need to be individualized. Sunny T. Varghese, M.B.B.S., M.D. Assistant Professor, Department of Psychiatry Dinesh Narayanan, M.B.B.S., D.P.M., M.D. Professor, Department of Psychiatry Deepa Dinesh Medical Student, Department of Psychiatry, Amrita Institute of Medical Sciences and Research Centre, Cochin, Kerala, India
References
1. Ala A, Walker AP, Ashkan K, et al: Wilson’s disease. Lancet 2007; 369:397–408 2. Lauterbach EC, Cummings JL, Duffy J, et al: Neuropsychiatric correlates and treatment of lenticulostriatal diseases: a review of the literature and overview of research opportunities in Huntington’s, Wilson’s, and Fahr’s diseases. A report of the ANPA Committee on Research. American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci 1998; 10:249–266 3. Kulaksizoglu IB, Polat A: Quetiapine for mania with Wilson’s disease. Psychosomatics 2003; 44:438–439
Oxcarbazepine-Induced Leukopenia To the Editor: Leukopenia is a well known adverse effect in epileptic patients treated with carbamazepine, but it has rarely been described with oxcarbazepine, particularly in adults. We describe a patient who developed reversible leukopenia with hyponatremia taking oxcarbazepine at high dosages. Case Report A 38-year-old man with partial epilepsy was admitted to our institute 1 year after starting treatment with oxcarbazepine in adjunctive therapy (previously he only assumed levetiracetam, 3000 mg/day, and clonazepam, 4 mg/day). Up to 1 week before admission, the patient had been taking a stable regimen of oxcarbazepine, 1800 mg/day, levetiracetam, 2000 mg/day, and clonazepam, 4 mg/day. Due to the occurrence of new partial seizures with secondary generalization, oxcarbazepine was quickly increased to 2400 mg/day. Except for epilepsy, the patient’s clinical history and physical examination were normal. At the admission, routine laboratory tests showed no relevant abnormalities except for hyponatremia (125 mmol/liter) and leukopenia (2800/mm3, 50% neutrophils). Laboratory tests for infectious diseases were negative. We proceeded with a scheduled tapering of oxcarbazepine, decreasing the dosage to 1800 mg/day and infusing lorazepam, 8 mg/day. Levetiracetam and clonazepam were continued. WBC count, 48 and 76 hours after reduction of oxcarbazepine, was 3100/mm3 and 3800/ mm3, respectively, with a parallel increase of sodium levels (128 and 131.6 mmol/liter). One week later oxcarbazepine dosage was in-
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LETTERS creased again to 2400 mg/day, and after 2 more days both WBC count and sodium values decreased (3200/mm3 and 125 mmol/liter, respectively). We decided to discontinue oxcarbazepine at a faster rate and replace it with topiramate (50 mg/day for 3 days, then slowly increased up to 200 mg b.i.d). Two days later, WBC count was 3800/ mm3 and 4 days later WBC count was 4800, with parallel normalization of sodium levels. A blood test performed a week later confirmed the normalization of sodium and WBC levels, and the patient was discharged with satisfactory seizure control. Discussion Oxcarbazepine is generally assumed to be safe with regard to the risk for adverse hematopoietic effects.1 Recently, pancytopenia associated with the introduction of oxcarbazepine was reported in an adult white woman.2 Isolated leukopenia has rarely been reported in children3 and never in adults. In
our patient we found a narrow correlation between the drug and leukopenia. During oxcarbazepine treatment at high dosages, the patient presented a significant reduction in WBC count, associated with low sodium level. Even if the patient’s treatment also included levetiracetam and clonazepam, a likely relationship had been postulated between the patient’s leukopenia and the increasing doses of oxcarbazepine, considering its structural analogies with carbamazepine. The complete normalization of WBC count after discontinuation of the drug confirmed our hypothesis. Sodium levels showed the same trend. Our experience confirms the possible association between oxcarbazepine and the development of blood dyscrasias. Besides pancytopenia and isolated thrombocytopenia,4 oxcarbazepine can also induce isolated leukopenia; this affect appears dosage-related and fully reversible after discontinuation of the drug. Therefore the adverse effects can occur in every moment of treat-
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ment and not only at its inception. In order to increase its safety, our study suggests that a careful evaluation of full blood count should be done during treatment with oxcarbazepine. Antonio Milia, M.D. Giuseppina Pilia, M.D. Maria Giuseppina Mascia, M.D. Jessica Moller, M.D. Eleonora Cocco, M.D. Maria Giovanna Marrosu, M.D. Institute of Neurology, University of Cagliari, Italy References
1. Hitiris N, Brodie MJ: Modern antiepileptic drugs: guidelines and beyond. Curr Opin Neurol 2006; 19:175–180 2. Calamaras MR, Stowe ZN, Newport DJ: Pancytopenia associated with the introduction of oxcarbazepine. J Clin Psychopharmacol 2007; 27:217–218 3. Serdaroglu G, Kurul S, Tutuncuoglu S, et al: Oxcarbazepine in the treatment of childhood epilepsy. Pediatr Neurol 2003; 28:37–41 4. Mahumud J, Mathews M, Verma S, et al: Oxcarbazepine-induced thrombocytopenia. Psychosomatics 2006; 47:73–74
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