Management of Clozapine-Induced Fever in a Child

Abstract

“Marie,” an 11-year-old African American girl of Caribbean descent with no previous psychiatric history, premorbid developmental impairments, or significant family psychiatric history, was admitted at the National Institute of Mental Health (NIMH) for participation in a longitudinal study of individuals with childhood-onset schizophrenia. She was reported to be a normally developing straight-A student who, not long before the onset of symptoms, had won a spelling bee. At age 10 years 3 months, after a brief trip to her father’s country of origin to attend a family funeral, she began to decompensate both emotionally and behaviorally. She had traveled to the region multiple times before, had not received any prophylactic medications or vaccines before the trip, and had no known sick contacts or exposures. Over the next 13 months, Marie progressively deteriorated psychiatrically. Through a detailed review of the records, discussions with her outpatient providers, and multiple interviews with both parents, it was found that the patient’s initial presentation was thought to be attributable to a major depressive episode with psychotic features, particularly given the context of the death of a close relative. Marie exhibited diminished emotional expression, avolition, alogia, and asociality. She subsequently received multiple antidepressant treatment trials, which were ineffective as she continued to deteriorate. Soon after her initial symptoms arose, she began to discuss paranoia and delusions and respond to internal stimuli, and she became increasingly disorganized. Antipsychotics were added to her regimen, without appreciable benefit. Although Marie’s symptoms did not fit clearly into a diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) (1), her providers, struggling with the severity and character of her symptoms, administered several trials of antibiotics, again with no effect. Over the following several months, she had numerous inpatient psychiatric admissions for physical aggression and psychosis, the longest of which lasted 3 months. During her admissions and the periods that followed, combinations of antidepressants, maximally dosed, and antipsychotics, minimally dosed, were administered with no effect. MRI and lumbar puncture were performed. The MRI was unremarkable. Results of the lumbar puncture suggested the possibility of an elevated intracranial pressure; the records were unclear, and on direct communication the providers could recall no further specifics. A repeat lumbar puncture was performed, and the results were normal. Nevertheless, apparently because of the patient’s lack of response to other treatments, she had received treatment with acetazolamide, which made no difference to her symptoms. Lumbar puncture was repeated at NIMH several months after the discontinuation of the acetazolamide and while the patient was symptomatic, and the results were again within normal limits. Subsequently, Marie’s providers discontinued antipsychotic and antidepressant prescriptions, instead providing as-need doses of clonazepam and directing her to emergency departments for agitation whenever her parents could not manage, and they referred her to NIMH for participation in the childhood-onset schizophrenia study. Since 1991, patients meeting DSM-IV criteria for schizophrenia with an onset of psychosis before age 13 have been recruited nationally for participation in a longitudinal study of individuals with childhood-onset schizophrenia conducted at NIMH. The protocol includes screening, evaluation, diagnosis, treatment optimization, and followup phases. Patients and first-degree relatives are interviewed over a period of 3 days for current and lifetime psychiatric disorders. Extended inpatient evaluation lasts up to 4 months and includes initial observation, medication taper, medication-free observation, and stabilization/ treatmentoptimizationphases. Beforeadefinitivediagnosis is made, medical causes for a patient’s presentation are aggressively explored, often with the aid of consulting specialties, and without limitation. Once diagnosed, the patient enters the treatment optimization phase and is given appropriate clinical treatment until stabilized. Longitudinal outpatient follow-ups are offered every 2 years for subsequent evaluation, and more frequently if indicated (2). Marie was screened by the childhood-onset schizophrenia team at NIMH. The patient and her parents were interviewed individually and as a group over a 3-day period using both clinical and structured interviews. The