Valproate Monotherapy in an SRI-Intolerant OCD Patient

Abstract

Sir: Risperidone, a recently introduced novel antipsychotic, is associated with a low incidence of seizures. During premarketing testing, seizures occurred in 0.3% (9/2607) of risperidone-treated patients (with dosages unrevealed), two in association with hyponatremia.1 To our knowledge, no postmarketing risperidone-associated seizure has been reported. We describe an elderly schizophrenic woman who developed a single seizure after 2 days of coadministration of risperidone, sulfamethoxazole-trimethoprim, and astemizole.Case report. Ms. A, a 64-year-old Chinese schizophrenic woman, had been physically healthy and devoid of any seizure or substance abuse history before this hospitalization. She failed adequate trials of two antipsychotics, sulpiride and flupenthixol. After 7 days of washout, risperidone was started at 1 mg b.i.d. on Day 1. However, a mild urinary tract infection occurred incidentally on the same day. Sulfamethoxazole (400 mg)-trimethoprim (80 mg) was thus coadministered b.i.d. On Day 2, the dosage of risperidone was increased to 2 mg b.i.d. A mild scalp itch appeared, and astemizole 10 mg/day was then prescribed. Surprisingly, 9 hours after taking the initial four doses (1 mg, 1 mg, 2 mg, and 2 mg) of risperidone, she experienced a single, witnessed, 1-minute generalized tonic-clonic seizure with a 5-minute postictal confusion period. Risperidone was discontinued immediately, and astemizole was withdrawn 1 day later. Sulfamethoxazole-trimethoprim was continued for 7 days. A thorough workup, including urine/blood routine, a biochemistry examination, an ECG and a head CT scan, produced negative findings, except bacteriuria and a mild fever. The electroencephalogram results before risperidone therapy and 1 day and 4 months after the seizure were all unremarkable. Her psychotic symptoms (e.g., auditory hallucinations) subsided abruptly after the seizure, but emerged again 15 days later. Consequently, risperidone was restarted at a lower dosage, 0.5 mg h.s., and was titrated over 2 days to 0.5 mg b.i.d. The psychotic symptoms receded on this regimen. She has now been free of seizures for 4 months. Antiseizure medications were not added. Astemizole, a peripherally acting H 1 antagonist, has not been reported to induce seizures in patients. In developing mice, astemizole, in contrast to other centrally acting H 1 antagonists, does not increase the durations of electrically induced seizures. However, among 1121 sulfamethoxazole-trimethoprim-treated inpatients participating in the Boston Collaborative Drug Surveillance Program, none developed seizures.4 Drug-drug interactions have not yet been reported among risperidone, astemizole, and sulfamethoxazole-trimethoprim. Studies to investigate the possibilities of their drug interactions are needed in the future.The initial risperidone dosing schedule of the present case had been used in the North American multicenter studies with the subjects aged 18-65 years. 5,6 Nonetheless, there is a paucity of data relating to the use of risperidone in elderly schizoph...

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