In order to reduce the risk of sudden death on anti-psychotics due to cardiac arrhythmia, I recommend that all patients take magnesium supplements, i.e., 250 mg twice a day.  Fortunately, magnesium also decreases the risk of developing diabetes, a risk much elevated in schizophrenia.  The cost-effectiveness of repeated cardiac monitoring has not been studied and I doubt its value.

Anti-Depressants and Lithium Increase QTc in Schizophrenic Patients: In a study of 19 schizophrenic women, mean QTc intervals significantly increased when an anti-depressant was added to their anti-psychotic (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. (24 ms) but not in 19 others treated with only an anti-psychotic (haloperidol, olanzapine, risperidone or clozapine)(-1 ms) (p < 0.01). The number of patients who exceeded the threshold of borderline QTc interval value (450 ms) differed between the two groups, with seven patients on added anti-depressants (38%) compared to one on anti-psychotics alone (7%) (p < 0,05). QT interval prolongation related to psychoactive drug treatment: a comparison of monotherapy versus polytherapy. Sala M, Vicentini A, et al. University of Pavia, Italy. Ann Gen Psychiatry. 2005 Jan 25;4(1):1; Patients on lithium had longer QTc intervals.  This was especially true with lower potassium levels and higher lithium levels. J Electrocardiol. 2005 Apr;38(2):148-51

Torsades de Pointes: FDA Has Received a Few Reports of Unexplained Deaths: FDA said it received several spontaneous reports of heart beat abnormalities and reports of unexplained sudden deaths among Geodon users.  I have been unable to find any numbers, but small numbers of unexplained deaths or deaths from known side-effects occur with many other medications including buproprion (Wellbutrin), olanzapine (Zypreza: due to olanzapine induced diabetes), desipramine, haloperidol (Haldol), and probably most other psychiatric medications.  I doubt that the death rate on Geodon is any higher than any other anti-psychotic and I think it is almost certainly much lower than the death rate in similar patients treated without an anti-psychotic. For that matter, aspirin probably causes thousands of deaths each year due to increased rates of hemorragic strokes but its good effects may outweigh its bad effects.

Torsades de Pointes: First Death Reported: Sudden death in a patient with Tourette syndrome during a clinical trial of ziprasidone. Scahill L, et al. Yale University. J Psychopharmacol. 2005 Jun;19(2):205-6.

Torsades de Pointes: QTc Prolongation Possible from Risperdal, Seroquel, Geodon: The author found nine cases were available in which drug-induced QTc interval prolongation was associated with new generation antipsychotic drug administration involving risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. No evidence of torsades de pointes appeared in any of the 9 cases. New Generation Antipsychotic Drugs and QTc Interval Prolongation. Vieweg WV. Medical College of Virginia. Prim Care Companion J Clin Psychiatry. 2003 Oct;5(5):205-215

Torsades de Pointes: High Dose Ziprasidone Not Cause QTc Problem: The maximum dose approved by the Food and Drug Administration is 160 mg/day. In a report of 15 patients given 240 to 320 mg/day, due to intractable psychotic symptoms there was an average increase of 3.4 msec from pre- to post-treatment, with a maximum post-treatment interval of 452 msec and no cases having a pre- to post- treatment QTc interval increase > 20 msec. No significant QTc interval changes with high-dose ziprasidone: a case series. Levy WO, Robichaux-Keene NR, Nunez C. VA Medical Center, Tampa, FL. J Psychiatr Pract. 2004 Jul;10(4):227-32.

Torsades de Pointes Increased with Haldol: Torsade de pointes, a polymorphic ventricular tachyarrhythmia, has been associated with both intravenous and oral haloperidol administration. The management of torsade de pointes consists of discontinuation of haldol, correction of electrolyte abnormalities, administration of magnesium sulfate and, if necessary, overdrive pacing. Torsade de pointes associated with the administration of intravenous haloperidol:a review of the literature and practical guidelines for use. Hassaballa HA, Balk RA. Rush-Presbyterian St Luke's. Expert Opin Drug Saf. 2003 Nov;2(6):543-7. Ed: Haloperidol is associated with a small increase in the rate of sudden death compared to alternative treatments.

Magnesium Supplementation Helps Torsades de Pointes: Saldanha Aoki M, Rodriguez Amaral Almeida AL, Navarro F, Bicudo Pereira Costa-Rosa LF, Pereira Bacurau RF. Ann Nutr Metab. 2004;48(2):90-4. Ed: This suggests that patients on ziprasidone (Geodon) should take magnesium. Of course, I recommend magnesium 250 mg once or twice a day for everyone since the research on the benefits of magnesium supplementation is so positive.

Magnesium: IV Treats Torsade de Pointes; Oral Prophylactically Reduces Extrasystoles: Magnesium is of great importance in cardiac arrhythmias. It increases the ventricular threshold for fibrillation. Sinus node refractoriness and conduction in the AV node are both prolonged. Main indications for intravenous application of magnesium are Torsade de pointes tachycardias, digitalis toxicity induced tachyarrhythmias and multifocal atrial tachycardias. Additionally, patients with ventricular arrhythmias due to overdoses of neuroleptics or tricyclic antidepressants may profit from i.v. magnesium. Monomorphic ventricular tachycardias and ventricular arrhythmias refractory to class III antiarrhythmics have been shown to respond to i.v. magnesium. Recent publications have documented that perioperative use of magnesium can reduce the incidence of arrhythmic events on the atrial and ventricular level. Oral magnesium has been used for many years in patients with symptomatic extrasystoles. Studies show that the incidence of extrasystoles as well as patients' symptoms are reduced during oral magnesium therapy. Significance of magnesium in cardiac arrhythmias. Stuhlinger HG, Kiss K, Smetana R. Universitatsklinik fur Nofallmedizin, Vienna, Austria. Wien Med Wochenschr. 2000;150(15-16):330-4. 

Magnesium: Low Levels Increase Arrhythmias and Torsade de Pointes: Hypomagnesemia is arrhythmogenic when combined with hypokalemia and bradycardia leading to a prolongation of the plateau phase of the action potential; magnesium administration suppresses triggered activities mainly by a direct inhibition of the development of triggered potentials; and lidocaine suppresses triggered potentials only indirectly by preventing the development of early afterdepolarizations due to the shortening effect on the APD. There is a high incidence of torsade de pointes with the hypokalemia and hypomagnesemia caused by a chronic diuretic therapy. There is also the marked effectiveness of intravenous Mg vs. the inconsistent clinical effects of lidocaine in controlling torsade de pointes. Antiarrhythmic and Arrhythmogenic Actions of Varying Levels of Extracellular Magnesium: Possible Cellular Basis for the Differences in the Efficacy of magnesium and Lidocaine in Torsade de Pointes. Takanaka C, Ogunyankin KO, et al. UCLA. J Cardiovasc Pharmacol Ther. 1997 Apr;2(2):125-134.

Magnesium: Low Levels Common Problem: Hypomagnesemia causes neuromuscular, neurological, and psychiatric difficulties as well as cardiac arrhythmias including torsade de pointes resulting in sudden death. Incidence of hypomagnesemia in hospitalized patients is common and there is a lack of clinical awareness. Hypomagnesaemia in postoperative patients: an important contributing factor in postoperative mortality. Siddiqui MN, Zafar H, et al. Aga Khan University, Karachi, Pakistan. Int J Clin Pract. 1998 Jun;52(4):265-7.

Magnesium: Coronary Heart Disease Decreased 23% in Health Professionals by Magnesium: In the Harvard 39,000 male health professional study during 12 years of follow-up, there were 1,021 non-fatal heart attacks, and 428 fatal ones. The age-adjusted relative risk (RR) of developing CHD in the highest quintile (median intake = 457 mg/day) compared with the lowest quintile (intake = 269 mg/day) was 0.73 (p <0.0001). After controlling for standard CHD risk factors and dietary factors, the RR was 0.82 (p = 0.08), i.e., an 18% decrease in heart attacks. For supplemental magnesium intake, the RR comparing the highest quintile to non-supplement users was 0.77, a 23% decrease. Magnesium intake and risk of coronary heart disease among men. Al-Delaimy WK, Rimm EB, Willett WC, Stampfer MJ, Hu FB. J Am Coll Nutr. 2004 Feb;23(1):63-70. Ed: Excellent research shows that higher intakes of magnesium, including with the aid of supplements, results in a lower risk of developing diabetes and hypertension.

Magnesium: Coronary Artery Disease Increased 150% by Low Magnesium Intake: The 7,172 men in the Honolulu Heart Program had a baseline average daily dietary magnesium intake of 268 mg, with a range of 50.3 to 1,138 mg. During 30 years of follow-up, 1431 cases of coronary heart disease were identified. Within 15 years of baseline dietary assessment, the age-adjusted incidence of such disease fell significantly in those with the highest daily magnesium intake (340 mg or more) compared to those with the lowest (186 mg or less) or an incidence of 4.0 per 1000 person-years versus 7.3 per 1000 person-years. After adjustment for a variety of other elements, including nutrient intake and cardiovascular risk factors, the excess risk in those with the lowest intake ranged from 1.5 to 1.8-fold. Robert D. Abbott, University of Virginia. Am J Cardiol 2003;92:665-669

Magnesium Supplementation Helps Heart: Studies indicate an association between magnesium deficiency and a poor prognostic outcome in patients who have had myocardial infarction. It therefore appears to be a reasonable prophylactic measure to monitor closely magnesium status in patients with coronary heart disease and other patients at risk of acute myocardial infarction, and to supplement with oral magnesium when clinically necessary. In addition, recent studies provide supportive evidence that supplementation of magnesium may reduce the incidence of fatal and nonfatal arrhythmias after an infarct. Case Western, Am J Cardiol 1989 Apr 18;63(14):35G

Magnesium: Magnesium Supplement Helps Blocked Coronaries: A Los Angeles study of oral magnesium supplement found that it increased blood flow and lengthened exercise tolerance in DB study of patients with blocked coronaries. Circ 2000;102:2353

Magensium: Coronary Artery Disease Helped by Magnesium in DB: In a DB PC study of 181 patients with half on 365 mg/day of magnesium, researchers found not just improved endothelium with the magnesium but also improved exercise tolerance with a decrease in chest pain and improved quality of life. Effects of oral magnesium therapy on exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease. Shechter M, Bairey Merz CN, Stuehlinger HG, Slany J, Pachinger O, Rabinowitz B. Am J Cardiol. 2003 Mar 1;91(5):517-21.

Asthma and Potassium-Lowering Drugs at Risk for Arrhythmia; QTc-Prolonging Drugs Only Minimal Risk in This Study: In a case-control study 501 patients hospitalized for nonatrial cardiac arrhythmias from 1987 to 1998 vs. matched controls, 39 of the cases used QTc-prolonging drugs. When compared to controls, patients with arrhythmias were only slightly more likely to be using QTC-prolonging drugs and it was far from being statistically nonsignificant (OR 1.2). However, there was a 890% increased risk of arrhythmias for patients with a history of asthma (OR 9.9) and 430% increased risk for patients using potassium-lowering drugs (OR 5.3 ). Therefore, be careful with the use of QTc-prolonging drugs in these specific patients. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias. De Bruin ML, et al. Utrecht, The Netherlands. . Am J Cardiol. 2003 Jan 1;91(1):59-62.

Main Psychiatric Drugs Affect QTc Interval: Haloperidol, Trazodone, Clozapine, Olanzapine, Carbamazepine, Tricyclics with Nortriptyline Not a Concern for Adults, Except the Elderly: The QT interval measuring depolarisation and repolarisation has, when lengthened, been implicated as a risk factor for the development of torsades de pointes and sudden death, particularly in patients predisposed to these complications due to cardiovascular impairment. In a review of all of the available literature and contacts with pharmaceutical firms, the greatest concern is concerns haloperidol, droperidol, pimozide and trazodone, the short-term use of thioridazine, pimozide, sertindole, nortriptyline, clomipramine, doxepin and the long-term use of clozapine, olanzapine and carbamazepine. Among the antidepressants, the tertiary tricyclic antidepressants (imipramine, amitriptyline and doxepin) appear to have a more general impact, while the secondary tricyclic antidepressants (nortriptyline, desipramine) may impact more on children and the elderly. Torsades de pointes appeared to occur with mirtazapine. Psychotropic drugs and the ECG: focus on the QTc interval. Goodnick PJ, et al. University of Miami. . Expert Opin Pharmacother. 2002 May;3(5):479-98

Being Elderly Risk Factor for QTc: ECGs were obtained from 101 healthy individuals and 495 psychiatric patients. Abnormal QTc was defined from the healthy reference group as more than 456 ms and was present in 8% of patients. Age over 65 years (odds ratio 3.0), use of tricyclic antidepressants), thioridazine (5.4), and droperidol (6.7) were predictors of QTc lengthening, as was antipsychotic dose (high dose 5.3; very high dose 8.2). QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients. Reilly JG, et al. University of Newcastle Upon Tyne, UK. Lancet. 2000 Mar 25;355(9209):1048-52.

Effects of Nortriptyline on ECG in Children and Teens Called Mild: In 82 children and adolescents treated with nortriptyline (NT), all patients with available EKGs and serum NT levels were included with the exception of those receiving concomitant antipsychotic agents. Forty-three percent of subjects were receiving medications in addition to NT. The average NT dose was 2.0 mg/kg yielding mean serum NT levels of 105 ng/mL. There was a linear relationship of NT dose (mg/kg) to serum NT levels (r = 0.50, p < 0.0001). NT treatment resulted in small increases in heart rate, and PR, QRS, and QTc intervals (all ps < 0.01), of similar magnitude in children and adolescents. Individuals with the highest baseline EKG indices had the least amount of change in those indices with NT treatment. There were only a few statistically significant associations between NT dose or serum NT levels and EKG parameters. NT treatment was significantly associated with the onset of asymptomatic sinus tachycardia (heart rate > 100 beats per minute), and prolongation of the EKG QRS (> 100 msec) and QTc (> 440 msec) intervals. The effect of NT on the EKG in this age group is mild. A retrospective study of serum levels and electrocardiographic effects of nortriptyline in children and adolescents. Wilens TE, et al. MGH-Harvard. J Am Acad Child Adolesc Psychiatry. 1993 Mar;32(2):270-7.

Nortriptyline Called Little Risk in 1st Degree AV Block or Hemiblock: Ten depressed, elderly patients with cardiac conduction abnormalities were given therapeutic doses of nortriptyline. Serial ECGs revealed no clinically significant adverse cardiac changes. These data, added to the findings of previous research, suggest that tricyclic antidepressants (TCAs) present little risk in patients with first degree atrioventricular block or hemiblock. Patients with bundle-branch block and bifascicular block are at greater risk of adverse cardiac sequelae but can be treated with TCAs. To maximize safety, the authors recommend monitoring serial ECGs and plasma TCA levels. The effect of nortriptyline in elderly patients with cardiac conduction disease. Dietch JT, et al. University of California--Irvine Medical Center. J Clin Psychiatry. 1990 Feb;51(2):65-7.

Quetiapine Case of Torsades with Hypomagnesemia: A 45-year-old woman developed a generalized seizure and 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. Quetiapine was a risk factor for QTc interval prolongation and torsade de pointes. Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapine. Vieweg WV, et al. Glen Allen, VA, USA. . Acta Psychiatr Scand. 2005 Oct;112(4):318-22