Schizophrenia Research 125 (2011) 302–303

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Schizophrenia Research

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Letter to the Editors

Third degree heart block followingintramuscular ziprasidone

Dear Editors,

The second generation antipsychotic ziprasidone is well-tolerated and efficacious in the treatment of adults withschizophrenia (Bentley et al., 2008) and bipolar disorder(Brook et al., 2000) and is available for intramuscular use inthe management of acute agitation associated with schizo-phrenia (Daniel et al., 1999; Geodon® (ziprasidone) [packageinsert], 2010). However, accumulating evidence suggests thatziprasidone is associated with prolongation of the QT interval(Geodon® (ziprasidone) [package insert], 2010). Nonetheless,there has been considerable debate surrounding the clinicalsignificance of QTc prolongation induced by ziprasidoneadministration (Glassman, 2005). To this end, reports of cardiacadverse events which are clearly linked to ziprasidone remainscarce and are these reports are often complicated by theadministration of multiple concomitant medications (Keck etal., 2003). Herein, we report a case of bradycardia with third-degree atrioventricular block (complete heart block) andsubsequent pulseless electrical activity following a singleintramuscular dose of ziprasidone in an elderly patient.

Ms. A is a 70-year-old, African-American female with ahistory of paranoid schizophrenia, dementia due to multipleetiologies (dementia of the Alzheimer's type and vasculardementia) and hypertension. She presented to the psychiatricemergency department with persecutory delusions andauditory hallucinations, and had refused to take any medica-tions for several weeks. She was admitted to the inpatientpsychiatric service and on the second day of the hospitaliza-tion, became acutely agitated and physically struck a staffmember. Intramuscular ziprasidone (20 mg) was adminis-tered; however, within 45 min of this injection, Ms. A lostconsciousness. At that time, she was pulseless and hypoten-sive and her physical examination was remarkable for absentpulses and signs of poor perfusion (e.g. pale oral mucosa andpoor capillary refill). Electrocardiographic monitoring dem-onstrated bradycardia (30–40 beats per minute) with a third-degree heart block. Cardiopulmonary resuscitation wasbegun, intravenous access was established, and atropineand epinephrine were administered intravenously (1 mg and10 mg, respectively) according to Advanced Cardiac LifeSupport protocol. Upon transfer to the intensive care unit,transcutaneous pacing was initiated in conjunction with brief

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ionotropic support (norepinephrine infusion, 5 μg/min)Complete blood counts (including hemoglobin and hemato-crit), liver function tests and serum electrolytes were alwithin normal limits with the exception of mild hypokalemia(3 mEq/L, normal range 3.5–5 mEq/L). Serially-obtainedserum troponin measurements did not suggest acute myo-cardial ischemia or infarction. Chest radiographs demonstrat-ed a normal cardiomediastinal silhouette and no evidence ofacute cardiopulmonary disease. Transthoracic echocardiog-raphy revealed normal left ventricular systolic function(60%), no ventricular wall motion abnormalities, normaatrial and ventricular sizes and no pericardial effusion waspresent. Moreover, administration of agitated saline did notreveal echocardiogrpahic evidence of an intracardiac shuntWithin 36 h, Ms. A had spontaneously converted to a normasinus rhythm, with a heart rate which was consistently in the90 s and a blood pressure of 130/70 mm Hg and she no longerrequired any inotropic support. Subsequent serially-obtainedelectrocardiograms did not demonstrate atrioventricularblock and revealed a normal QTc between 420 and 450.

This case demonstrates a potentially life-threatening sideeffect of ziprasidone which has been rarely reported in theliterature, and to our knowledge, has never been reported in apatient treated with ziprasidone as monotherapy. TheNaranjo adverse event score (Naranjo et al., 1981) for thisparticular event (7) is consistent with a probable likelihood ofthe patient's third-degree atrioventricular block being asso-ciated with ziprasidone. Although pre-treatment, baselinelaboratory and electrocardiographic data are unavailable, it islikely that a number of clinical and psychopharmacologicfactors may have influenced this reaction. Specificallyziprasidone was administered parenterally which has beenassociated with higher peak concentrations as compared tooral administration (Geodon® (ziprasidone) [package insert]2010). In addition, the patient's advanced age, history ofhypertension, and even history of schizophrenia may havepredisposed Ms. A to develop cardiac disease. To this endpatients with schizophrenia may be at increased risk forcardiovascular disease, including atherosclerosis and suddendeath, andmay bemore likely to make lifestyle choices whichpredispose to cardiovascular disease (e.g. smoking, sedentarylife style, etc.) (Strom et al., 2008). Importantly, theatrioventricular block and subsequent hemodynamic col-lapsewhich occurred following intramuscular ziprasidone inthis patient who was not receiving any concomitantmedications provides evidence which supports the potentialink between QTc prolongation and a life-threateningarrhythmia. Clinicians should remain vigilant with regard

303Letter to the Editors

to the possibility that ziprasidone could precipitate seriousarrhythmias.

Role of Funding SourceNo funding source.

ContributorsDr. Tambyraja was involved in the clinical care of the patient described

herein. Both authors prepared and edited this report.

Conflict of InterestDr. Tambyraja reports no conflicts of interest. Dr. Strawn has received

research support from the American Academy of Child & AdolescentPsychiatry; honoraria from the American Academy of Child & AdolescentPsychiatry; and travel awards from the Anxiety Disorders Association ofAmerica and the American Psychiatric Institute for Research and Education(APIRE).

AcknowledgementsNone.

References

Bentley, M.L., Biscardi, F.H., Butcher, C., Levitov, A., 2008. Inadvertentadministration of intravenous ziprasidone leading to bradycardia andQT interval prolongation. Ann. Pharmacother. 42 (6), 902–903.

Brook, S., Lucey, J.V., Gunn, K.P., 2000. Intramuscular ziprasidone comparedwith intramuscular haloperidol in the treatment of acute psychosis. J.Clin. Psychiatry 61 (12), 933–941.

Daniel, D.G., Zimbroff, D.L., Potkin, S.G., Reeves, K.R., Harrigan, E.P.,Lakshminarayanan, M., 1999. Ziprasidone 80 mg/day and 160 mg/dayin the acute exacerbation of schizophrenia and schizoaffective disorder:a 6-week placebo-controlled trial. Neuropsychopharmacology 20 (5),491–505.

Geodon® (ziprasidone) [package insert]. 2010. Pfizer. New York, NY.Glassman, A.H., 2005. Schizophrenia, antipsychotic drugs, and cardiovascular

disease. J. Clin. Psychiatry 66 (suppl 6), 5–10.

Keck, P.E. Jr, Versiani, M., Potkin, S., West, S.A., Giller, E., Ice, K., et al., 2003.Ziprasidone in the treatment of acute bipolar mania: a three-week,placebo-controlled, double-blind, randomized trial. Am. J. Psychiatry 160(4), 741–748.

Naranjo, C.A., Busto, U., Sellers, E.M., Sandor, P., Ruiz, I., Roberts, E.A., et al.,1981. A method for estimating the probability of adverse drug reactions.Clin. Pharmacol. Ther. 30 (2), 239–245.

Strom, B.L., Faich, G.A., Reynolds, R.F., Eng, S.M., D'Agostino, R.B., Ruskin, J.N.,et al., 2008. The Ziprasidone Observational Study of Cardiac Outcomes(ZODIAC): design and baseline subject characteristics. J Clin Psychiatry69 (1), 114–121.

Rabindra TambyrajaCincinnati Children's Hospital Medical Center, Department of

Pediatrics, Division of Child & Adolescent Psychiatry, Cincinnati,Ohio 45229, United States

Jeffrey R. StrawnUniversity of Cincinnati College of Medicine, Department of

Psychiatry, Cincinnati, Ohio 45220, United StatesCincinnati Children's Hospital Medical Center, Department of

Pediatrics, Division of Child & Adolescent Psychiatry, Cincinnati,Ohio 45229, United States

Corresponding author. Department of Psychiatry,University of Cincinnati College of Medicine,

260 Stetson Street, Suite 3200, ML 0559, Cincinnati,OH 45267-0559, United States. Tel.: +1 513 558 4489;

fax: +1 513 487 6696.E-mail address: strawnjr@uc.edu.

27 March 2010