Psychosomatics 41:63-65, February 2000
© 2000 The Academy of Psychosomatic Medicine
QT Interval Prolongation Associated With Quetiapine (Seroquel) Overdose
Prashant Gajwani, M.D.,
Leopoldo Pozuelo, M.D., and
George E. Tesar, M.D.
Received June 3, 1999; accepted June 14, 1999. From the Department of Psychology and Psychiatry, Cleveland Clinic Foundation (CCF), 9500 Euclid Avenue, Cleveland, OH 44195. Address correspondence and reprint requests to Dr. Tesar, Department of Psychiatry and Psychology, CCF, 9500 Euclid Avenue, Cleveland, OH 44195.
Key Words: Antipsychotics • Quetiapine • QT Interval
Haloperidol and other typical antipsychotics are known to cause cardiac conduction abnormalities, including QTc interval prolongation on an electrocardiogram (ECG).1–4 Newer antipsychotics, such as olanzapine, risperidol, and quetiapine, have a reputation for cardiovascular safety.5–10 We report a case of quetiapine overdose that was associated with clinically significant QT interval prolongation.
Case Report
A 19-year-old, single, Caucasian man with a history of paranoid schizophrenia and past suicide attempts was found by his parents in a lethargic state. He had vomited after ingesting about 50 200-mg tablets of quetiapine (Seroquel). The emergency medical service team found the patient comatose, hypotensive, and tachycardiac and notified the aeromedical transport team, who assigned the patient a Glasgow Coma Scale (GCS) score of 6 (range: 3–15, with 15 being fully alert and oriented). The patient was intubated, and intravenous saline was started. He was transported to our facility via helicopter. On arrival in the emergency department (ED), his blood pressure was 180/83, pulse was 138, and rectal temperature was 36.3°C. Pupils were 3 mm, equal, and reacted sluggishly to light; extremities were flaccid; and his GCS score had dropped to 3. The rest of the physical examination was normal. With an FIO2 (forced inpiratory oxygen) of 100%, his arterial blood gas analysis revealed a pH of 7.34; PO2 (partial pressure of oxygen): 547; pCO2 (partial pressure of carbon dioxide): 2–42; HCO3 (bicarbonate): 23; potassium: 3.3 (rechecked 3 hours later, potassium was 4.1); glucose: 137; calcium: 8.3; and magnesium: 1.7. Blood toxicology screening was negative for tricyclics, acetaminophen, salicylates, and alcohol. Other medications he had been prescribed included clonazepam and fluvoxamine; there was no indication that he had ingested anything other than quetiapine in the drug overdose.
About 2 hours postingestion, the QTc was 581 msec (Figures 1 and 2). The patient was given activated charcoal in the ED and transferred to the medical intensive care unit. Rapid improvement in neurological status was evident 5.5 hours postingestion, indicated by a GCS of 7. Magnesium supplementation was administered 14 hours postingestion, when the QTc was 710 msec. At 19 hours postingestion, the GCS was 11. He was extubated 24 hours after the overdose. At 27 hours, blood pressure was stable and the QTc had returned to 440 ms. Persistent tachycardia resolved by the third day.
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FIGURE 2. Electrocardiogram of MrA, 11:38 P.M., September 4, 1998 Note: QTc (ms)=710 msec; QRS=104 msec; QT=562 msec; VR=96 bpm
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During the hospitalization, the patient complained of intermittent chest pain. ECG and cardiac enzymes revealed no evidence of myocardial insufficiency or infarction. The patient was transferred to the inpatient psychiatric unit, where he admitted to ingesting 48 tablets of quetiapine (9,600 mg) 72 hours earlier. He was discharged home on quetiapine after 5 days of psychiatric inpatient hospitalization, as he had demonstrated treatment refractoriness to other antipsychotics.
DISCUSSION
We present a case of QTc prolongation with quetiapine overdose. To our knowledge, this is the first case of QTc prolongation reported with quetiapine use. Our patient was also taking fluvoxamine, which is an inhibitor of P4503A4. Quetiapine is also metabolized by this enzyme; therefore, combined use with fluvoxamine could have resulted in an increased plasma concentration of quetiapine. Electrolyte imbalance is another possible potentiating factor.
Two cases of quetiapine overdose have been reported in the literature. The amounts consumed were 9,600 mg and 10,000 mg, respectively. In one case, hypokalemia associated with first-degree heart block was observed; in the second case, no cardiac conduction abnormality was reported.5,6 In our case, the low serum potassium and low-normal magnesium level may have contributed to the QT prolongation. However, the serum potassium was 4.1 when remeasured, and it is unlikely that either of these factors alone caused the prolongation of QTc. Other predisposing factors that must be considered (e.g., congenital prolonged QT syndrome, other conduction disease) were not present.
Antipsychotics can affect cardiac conduction through either anticholinergic or quinidine-like properties. A high prevalence of QTc prolongation has been reported in patients treated with antipsychotics, compared with a control group.3 Underlying cardiac disease appears to be a predisposing factor in the development of QTc prolongation and Torsades de pointes in patients treated with typical antipsychotics medication.4
The mechanism by which quetiapine may have caused QTc prolongation is not known. Atypical antipsychotics, such as clozapine, sertindole, risperidone, and olanzapine, can prolong QT interval in perfused feline heart in a concentration-dependent manner attributable to an effect on cardiac potassium channels that resemble those of humans.12
Our case suggests that it is important to identify pretreatment cardiac conduction abnormalities and other risk factors associated with QT interval prolongation when prescribing quetiapine, especially in high dosage or during concomitant use of fluvoxamine or other P4503A4 inhibitors. The authors would recommend checking a baseline ECG before starting treatment.
REFERENCES
- Tan Hl, Hou CJY, Lauer MR, et al: Electrophysiologic mechanisms of long QT interval syndromes and Torsades de pointes. Ann Intern Med 1995; 122:701–704[Abstract/Free Full Text]
- Liberatore MA, Robinson DS: Torsade de pointes: a mechanism for sudden death associated with neuroleptic drug therapy? J Clin Psychopharmacol 1984; 4:143–146[Medline]
- Warner JP, Barnes TRE, Henry JA: Electrocardiographic changes in patients receiving neuroleptic medication. Acta Psychiatr Scand 1996; 93:311–313[Medline]
- Metzger E, Friedman R: Prolongation of corrected QT and Torsades de pointes cardiac arrhythmia associated with haloperidol in the medically ill. J Clin Psychopharmacol 1993; 13:128–132[Medline]
- Harmon T, Krenzelok E: Rapid loss of consciousness from acute quetiapine overdose (abstract 155). J Toxicol 1997; 35:546
- Nudelman E, Vinuela LM, Cohen CI: Safety in overdose of quetiapine: a case report (letter). J Clin Psychiatry 1998; 59:433 [Medline]
- Seroquel (Quetiapine fumerate) tablet: Professional information brochure. Zeneca Pharmaceuticals
- Fogel J, Diaz JE: Olanzapine overdose (letter). Ann Emerg Med 1998; 32:275–276
- Elian AA: Fatal overdose of olanzapine. Forensic Sci Int 1998; 91:231–235[CrossRef][Medline]
- Seroquel: a putative atypical antipsychotic drug with serotonin- and dopamine-receptor antagonist properties: preclinical and early clinical trials in schizophrenia (ACADEMIC HIGHLIGHTS). J Clin Psychiatry 1995; 56:438–445[Medline]
- Arvanitis LA, Miller BG, and the Seroquel Trial 13 Study Group: Multiple fixed doses of "Seroquel" (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry 1997; 42:233–246[CrossRef][Medline]
- Drici MD, Wang WX, Liu XK, et al: Prolongation of QT interval in isolated feline heart by antipsychotic drugs. J Psychopharmacol 1998; 18:477–481
- Braunwald E: Heart Disease, 5th Edition. Philadelphia, PA, WB Saunders, 1996
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