Tuberous Sclerosis With Psychosis

Letters QTc Prolongation: Possible Association With Risperidone and/or Haloperidol TO THE EDITOR: Prolongation of the electrocardiographic QT interval is an area of concern when prescribing antipsychotic drugs. The QT interval usually is inversely proportional to heart rate and should generally be ⱕ1/2 of an R-R timing. A corrected QT (QTc) of 440 msec or less is considered normal. Values over 500 msec are associated with a substantially increasing risk of dangerous cardiac dysrhythmias. The QTc exhibits high variability with age, gender, metabolic factors, and use of certain medications. Several antipsychotic drugs, such as chlorpromazine, haloperidol, thioridazine, olanzapine, quetiapine, and ziprasidone can induce QTc interval prolongation. The clinical vignette presented here documents a patient with QTc prolongation that was temporally associated with risperidone and haloperidol administration. Case Report Mr. A, a 46-year-old white man with a history of schizophrenia and no past heart disease, was hospitalized secondary to overt psychosis. He had previously been given oral risperidone, 4 mg/day, but outpatient compliance was questioned. On hospital days 1 and 2, he received risperidone, 2 mg/day. Later, when agitated and tachycardic (pulse rate of 124 bpm), 5 mg of haloperidol and 2 mg of lorazepam were adjunctively administered one time. Two hours later, Mr. A remained tachycardic, and an ECG was ordered, revealing sinus tachycardia (111 bpm), with a QTc of 504 msec. No such conduction delay had been noted on an

ECG obtained 4 months earlier. Risperidone and haloperidol were discontinued because of the QT prolongation and replaced with quetiapine, 150 mg/ day. An ECG on day 3 showed sinus tachycardia (133 bpm), with a QTc of 451 msec; an echocardiogram was remarkable only for paradoxical basilar septal motion of the left ventricle. On day 4, an ECG revealed sinus tachycardia (106 bpm) and QTc of 400 msec. Seven subsequent daily tracings demonstrated an absence of tachycardia and QTc intervals below 407 msec. Four serum electrolyte panels, including measures of calcium and magnesium levels, as well as hepatic enzymes, cardiac enzymes, and thyroid function studies produced results within normal limits. Mr. A never reported cardiovascular complaints, and no further signs of cardiac concern were observed. Discussion This presentation illustrates a case of QTc prolongation noted after a patient with no previous cardiac history and a previously normal ECG received risperidone and haloperidol. It is unclear whether risperidone, haloperidol, or a combination of the two was responsible for this concern. Both risperidone and haloperidol can induce QTc prolongation. It is possible that concurrent administration had a synergistic effect. QTc interval prolongation has been reported in two patients after risperidone overdose1,2 and in eight of 380 subjects in a double-blind study.3 There has also been a case of fatal pulseless electrical activity with QTc prolongation documented after initiation of risperidone.4 Haloperidol, similarly, can cause QTc prolongation in dose-response relationships at quantities over 50 mg/day;5 2% of the individuals treated with intrave-

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nous haloperidol had a QTc interval of over 500 msec.6 The ECG is an important tool in detecting cardiac conduction delays. Such monitoring adds a safety factor, especially in cases of antipsychotic drug co-administration. Jayasree J. Nandagopal, M.D. Jeffrey M. Craig, B.S. Steven Lippmann, M.D. Louisville, Ky.

References

1. Brown K, Levy H, Brenner C, Leffler S, Hamburg EL: Overdose of risperidone. Ann Emerg Med 1993; 22:1908–1910 2. Lo Vecchio F, Hamilton RJ, Hoffman RJ: Risperidone overdose (letter). Am J Emerg Med 1996; 14:95–96 3. Package insert: Risperdal (risperidone). Titusville, NJ, Janssen, December 1994 4. Ravin DS, Levenson JW: Fatal cardiac event following initiation of risperidone therapy. Ann Pharmacother 1997; 31:867– 870 5. Lawrence KR, Nasraway SA: Conduction disturbances associated with administration of butyrophenone antipsychotics in the critically ill: a review of the literature. Pharmacotherapy 1997; 17:531–537 6. Sharma ND, Rosman HS, Padhi ID, Tisdale JE: Torsades de pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol 1998; 81:238– 240

Tuberous Sclerosis With Psychosis TO THE EDITOR: Tuberous sclerosis is a neurological disease characterized by the triad of facial adenoma sebaceum, epilepsy, and mental retardation.1 An association with schizophrenia has been documented. (2; 3, pp. 1566– 1571) Our clinical vignette describes a man with tuberous sclerosis who became psychotic but improved when given antipsychotic medication. 521

Letters Case Report Mr. A was a 45-year-old African American man with tuberous sclerosis and tonic-clonic seizures since he was 7 years old. Treatment modalities included medications, a surgical partial corpus callosum and right frontal lobe resection, and vagus nerve stimulation. His epilepsy was stabilized with felbamate, divalproex, chlorazepate, and clonazepam. Mr. A became functional, despite occasional seizures. To decrease his exposure to medication, divalproex had been discontinued 9 months previously. That precipitated a decline in his mental status, with disorganized, isolative ideation and a worsening in ictal frequency. Restarting divalproex did not improve the condition. Five months later, Mr. A experienced visual and auditory hallucinations with paranoid delusions, resulting in his first psychotic episode. An EEG revealed encephalopathy, unchanged from a previous tracing, with background slowing, periods of multifocal slowing, and epileptiform discharges. Brain imaging by coaxial tomogram of the head was normal, except for diffuse atrophy and calcification at the right frontal horn, falx, and dura. Mr. A refused fundoscopic examination; however, an ophthalmological evaluation revealed normal vision with defects of the visual field. Mr. A’s laboratory profile was unremarkable; his felbamate and divalproex blood levels were in the therapeutic range, despite potential drug interactions that could increase both of their concentrations. (3, p. 1648) Before deterioration, Mr. A had been able to read and perform activities of daily living. Now he was paranoid and distractible. Olanzapine, 15 mg/ day, had been given to him with no benefit. Once he was admitted to our 522

facility, risperidone was titrated to 8 mg/day. His thoughts gradually became more organized and improved on this moderately high dose. Mr. A then reported no auditory hallucinations and was less paranoid, with considerable global improvement in mental function. This progress was sustained.

who show psychosis with tuberous sclerosis. Karim Sedky, M.D. Tiffany Hughes, M.D. Kamalullah Yusufzie, M.D. Steven Lippmann, M.D. Philadelphia, Pa. References

Discussion Tuberous sclerosis is characterized by hamartomas affecting much of the body, including the brain (tubers), retina (phakomas), and skin. (3, pp. 1566– 1571; 4) Associated eye signs include iris depigmentation, poliosis, and keratoconus. Hypomelanotic macules, nevi, and ash leaf spots are also observed. Cardiac rhabdomyomas have also been documented. (3, pp. 1566– 1571; 4) Psychosis has been reported in such patients;2 brain tubers, subependymal calcification, giant cell tumors, and retinal phakomas (3, pp. 1566– 1571) might be the cause. Postictal confusion with delirium can occur and could have been present in our case. This illness would be classified as a psychotic disorder because of the medical condition. The literature lacks specific treatment recommendations for psychosis in tuberous sclerosis. Our patient had a good response to high-dose risperidone without side effects. His psychosis diminished during antipsychotic pharmacotherapy, with improvement in personal function and thought processes. Tuberous sclerosis is an uncommon condition and its association with psychosis is even less frequently observed. Since it is a rare presentation, research into therapeutic options is limited. We hope that our clinical experience and the improvements noted might be of help to physicians caring for people

1. Kaufman DM: Clinical Neurology for Psychiatrists. Philadelphia, WB Saunders, 2001, p 329 2. Herket E, Wald RO: Tuberous sclerosis and schizophrenia. Dis Nerv System 1972; 33:439–445 3. Bradley WG, Daroff RB, Fenichel GM, Jankovic J: Neurology in Clinical Practice. Newton, Mass, Butterworth-Heinemann, 1996 4. Adams JH, Duchen LW: Neuropathology. New York, Oxford University Press, 1992, pp 604–610

Trauma in a Nurse After Patient Suicide TO THE EDITOR: The suicide of a patient has a major impact on the medical staff. Most of the literature has reported the responses of psychiatrists and psychotherapists after a patient’s suicide, but few articles have dealt with nurses’ responses,1,2 especially in a nonpsychiatric setting. Furthermore, these works reported nurses’ psychological responses mainly from the point of view of their bereavement and grief reactions.3 In this letter, we describe an oncology nurse who needed a psychiatric consultation because of traumatic symptoms after a patient suicide. Case Report Ms. A, a nurse in her early 20s, had been working in a cancer center hospital. One day, she was on the midnight shift with a recently graduated nurse, Ms. B. Ms. B had been making the regular nursing rounds, when she entered the private room of a male patient in

Psychosomatics 44:6, November-December 2003