Letters to the Editor
Antipsychotic-Induced QTc Interval Prolongation
Case Report
Mr X is an African male, aged 45 years, with a history of chronic paranoid schizophrenia and cocaine abuse. He was admitted to the VAMC psychiatric inpatient unit owing to exacerbation of psychotic symptoms. Mr X was experiencing command auditory hallucinations, directing him to kill himself, along with paranoia, thought insertion, thought broadcasting, and thought withdrawal. During the week prior to admission, Mr X had relapsed to using cocaine, and psychotic symptoms had been worsening, despite treatment with intramuscular haloperidol. On admission, his evaluation comprised a detailed psychiatric, medical, substance abuse, and psychosocial history as well as the relevant laboratory studies. He had a white blood cell count of 6.6; hemoglobin count, 14.7; hematocrit count, 44.8; and platelet count, 285 000. Electrocardiogram on admission revealed QTc interval of 428 milliseconds. Admission vital signs were the following: temperature 97.7, pulse 75, respirations 20, blood pressure 115/74.
We noted that Mr X, who had been sober and involved in substance abuse treatment prior to the week before admission, had failed at least 2 trials of typical and atypical neuroleptics. In light of the history and severity of symptoms, we decided a trial of clozapine would be the most appropriate course of treatment. Haloperidol was discontinued. Mr X was started on 25 mg daily of clozapine, with the dosage gradually increased to 150 mg in 2 weeks. Electrocardiogram (EKG) and laboratory values were monitored regularly. Within 14 days of clozapine treatment, QTc interval had increased to 472 milliseconds, and the patient was tachycardic, with heart rate over 100 beats per minute. At this point, an internal medicine consult was obtained. The recommendation was to immediately discontinue clozapine because of the risk for potentially fatal arrhythmia, such as torsade de pointes. Thus clozapine, which had so far been effective in controlling psychotic symptoms, was discontinued. Quetiapine was initiated the next day, and monitoring of vital signs, laboratory values, and EKG was continued. Over the next 3 days, the QTc interval returned to baseline of 428 milliseconds and remained at baseline throughout the patients hospitalization. Vital signs also remained stable with heart rate returning to baseline level. To treat Mr Xs psychosis effectively, quetiapine dosage was titrated to the maximum recommended daily dosage of 800 mg. Mr X tolerated quetiapine well and was safely discharged from the hospital in 2 weeks time. He continues in outpatient treatment and remains stable.
Drug-induced QTc prolongation, though not very common, is potentially fatal. Usually, multiple risk factors need to be present to precipitate arrhythmia, including drug use, such as cocaine (1). In contrast, substance abuse is common among schizophrenia patients, with up to 50% meeting criteria for comorbid substance abuse or dependence. Cocaine abuse is especially problematic because it complicates psychosis and has been shown to prolong QT and QTc intervals and to lead to lethal arrhythmias (2). As our case shows, comorbid cocaine abuse can increase the risk of antipsychotic-induced cardiotoxicity. Though clozapine pharmacotherapy remains an important option for patients with treatment resistant schizophrenia, with other treatment resistant psychotic disorders, and (or) with severe tardive dyskinesia, other treatment options such as quetiapine can be highly effective (3), as shown in our case. Patient safety depends on careful screening for risk factors associated with QT/QTc interval prolongation, especially comorbid substance abuse; close monitoring once antipsychotic treatment is initiated; and appropriate follow-up treatment, both for the primary psychotic disorder and for comorbid substance abuse.
References
1. Roe CM., Odell KW, Henderson RR. Concomitant use of antipsychotics and drugs that may prolong the QT interval. J Clin Psychopharmacol 2003;23:197200.
2. Chakko S, Sepulveda S, Kessler KM., Sotomayor MC, Mash DC, Prineas RJ, and others. Frequency and type of electrocardiographic abnormalities in cocaine abusers. Am J Cardiol 1994;74:7103.
3. Warner B, Hoffman P. Investigation of the potential of clozapine to cause torsade de pointes. Adverse Drug Reaction Toxicology Review 2002;21:189203.
Vijay Dewan, MD, FRCPC
Barbara Ann Roth, MD
Omaha, Nebraska
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