Correspondence RISPERIDONEOVERDOSE To the Editor:--Risperidone is a benzisoxazole derivative avail- able for the treatment of schizophrenia and other psychotic disorders. The drug is a serotonin type 2 receptor antagonist (similar to clozapine), and dopamine type 2 receptor antagonist (similar to haloperidol). It is also an antagonist at the alpha- adrenergic and histamine H1 receptors. 1,z The mechanism of its antipsychotic action is unknown. Risperidone has two distinct advantages over traditional antipsychotic medications. First, as a serotonin antagonist, it treats the "negative" symptoms of psycho- sis (apathy, withdrawal, and unresponsiveness) as well as the "positive" symptoms (hallucinations). The second advantage is its low incidence of extrapyramidal side effects.l-4 In one previous case of an apparent overdose in the literature, electrocardiogram (ECG) abnormalities (prolonged QT and wid- ened QRS) and electrolyte abnormalities (hypokalemia and hypona- tremia) developed) In addition, the package insert reports an unpublished case involving an estimated overdose of 36 mg that was associated with a seizure. 4 However, no medical history or possible concurrent ingestions are mentioned in this report or available by the drug company. In addition, there are two cases of risperidone-induced neuroleptic malignant syndrome associated with prior use of sulpride in the elderly. 4 The following case report of apparent acute ingestion is presented to help define the clinical signs and symptoms of its toxicity. Report of a Case. A 2l-year-old woman stated that she had taken 60 2-rag tablets of risperidone 2 hours before presentation. It was confirmed that she filled this prescription on the day of admission. She had a history of psychosis and depression, with 4 previous suicide attempts and she had been on risperidone for the 2 months prior to presentation. The patient denied alcohol use, concurrent ingestions, other medications, or diuretic abuse. On presentation she complained of somnolence and dry mouth. Physical examination found a lethargic woman who was oriented to person, place, and time. Her weight was 80 kg. Vital signs were: blood pressure, 118/68 mm Hg without orthostatic changes; heart rate, 98 beats/rain; temperature, 36.5°C rectally; and respirations, 18 breaths/rain. The patient's skin was dry, and urinary catheteriza- tion revealed 150 mL of urine. No other abnormalities were noted. The patient was placed on an ECG monitor. Large-bore orogas- tric tube lavage was not performed. The patient received 50 mg of activated charcoal by nasogastric tube every 2 hours, for a total of 3 doses and an initial dose of 8 oz magnesium citrate. An ECG on arrival showed normal sinus rhythm at 99 beats/rain. The QRS duration was 80 ms, with an axis of 42 degrees, and the terminal 40 ms was in the left axis. The initial corrected QT interval (QTc) was 400 ms. Initial laboratory evaluation included serum chemistries, complete blood count, creatine kinase, routine urinalysis, and serum toxicologic evaluation. Abnormalities included a potassium of 3.4 mEq/L, chloride of 114 mEq/L, HCO3 of 16 retool/L, magnesium of 1.5 mg/dL, and calcium of 8.9 mg/dL. The serum toxicological screens showed no acetaminophen, alcohol, salicy- fates, benzodiazepine, barbiturates, or tricyclic antidepressants. The tricyclic antidepressant screen was evaluated using an Abbott ADX/TDX (Abbott, North Chicago, IL) via fluorescent immunoas- say. A risperidone level was not available. Approximately 4 hours after arrival the patient received a 2-g magnesium sulfate intrave- nous infusion to correct the magnesium level. A repeat ECG demonstrated a QTc corrected to her baseline of 380 ms immedi- ately after magnesium infusion. The patient then received 40 mEq potassium chloride intravenously: Eight hours into her emergency department course her repeat electrolyte levels were normal. A review of her old chart documented normal serum chemistries and ECG 3 weeks prior to this ingestion. Her somnolence and dry mouth resolved spontaneously. She was uneventfullymonitored for 24 hours and transferred to the psychiatric service. Risperidone is a new agent with serotonin and dopamine receptor activity used in the treatment of various psychotic behaviors. One previous report described a patient who presented without serious clinical side effects but with various ECG abnormali- ties including a QRS interval of 112 ms and QTc prolongation of 565 ms. The patient also had laboratory data significant for a sodium of 125 mEq/L and a potassium level of 2.9 mEq/L. The magnesium level was unknown. The patient's ECG and laboratory data were corrected with sodium and potassium replacement. Risperidone levels were not available. The patient was monitored and observed to be without further toxicity for 24 hours. 5 Our patient was a 21-year-old woman who ingested a similar quantity (120 mg) of risperidone. She developed minor cardiac and electrolyte abnormalities. Her QTc dispersion was approximately 20 ms as compared with her baseline. The patients' magnesium was replaced and her borderline prolonged QT~ resolved. She also received potassium supplementation. She received repeated doses of activated charcoal until her laboratory and physical abnormali- ties returned to baseline. Unlike previous reports, this case did exclude tricyclic antidepressant overdose by serum toxicology. Adverse reactions with this drug include extrapyramidal reac- tions thought to be secondary to dopamine antagonism. It may produce postural hypotension, as might be expected from the alpha-adrenergic antagonism, but this effect is slight, occurs initial/y, and tends to be more pronounced in the elderly?,3 A case of an alleged overdose of risperidone is discussed. Little is known about the toxicity of risperidone in acute overdose, its affinity for serotonin type 2 receptors without harmful hematologic effects makes it a safe replacement for clozapine, and it will soon gain widespread use for the treatment of schizophrenia and other psychotic disorders. Because of this, risperidone overdoses will become increasingly more common. The clinician caring for these patients should be vigilant for the possibility of seizure (unpublishedobservation, Janssen Pharmaceu- ticals), hypotension, tachycardia, sedation, and extrapyramidal symptoms. Furthermore, electrolyte (including magnesium) and ECG abnormalities (prolonged QT interval) may be seen. Our treatment in this case was mainly supportive, with correction of electrolyte abnormalities. No general conclusions about the toxic- ity of risperidone in the overdose setting are supported by this case report. However, evidence is mounting that toxicity includes CNS depression and cardiac and electrolyte abnormalities. The clinical course of this patient was benign except for ECG and electrolyte abnormalities. FRANK LO VECCH[O, DO Emergency Medicine Residency Mr. Sinai School of Medicine Integrated Residency in Emergency Medicine Beth Israel Medical Center and Elmhurst Hospital Center RICHARD J. HAMILTON, MD ROBERT J. HOVVMAN, MD Medical Toxicology Fellowship Program New York City Poison Center Departments of Surgery and Emergency Medicine New York University School of Medicine References 1. Leysen JE, Gommeren W, Eens A, et al: Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther 1988;247: 661-670 95