Although torsade de pointes is generally self-terminating and generates few hemodynamic symptoms, this arrhythmia must be considered potentially life-threatening because of its tendency to recur and to deteriorate into ventricular fibrillation. Hence adequate monitoring should be implemented early when a drug is introduced that may prolong the QT interval (
+9). Treatment of drug-induced torsade de pointes consists of discontinuation of the offending agent and treatment of the arrhythmia, either with electrical atrial pacing or with medications. Treatment is best managed in a medical intensive care unit.
It is especially important to keep in mind that patients with major psychiatric disorders tend to have more risk factors for QT interval prolongation than the general population. The risk factors include treatment with other drugs that also prolong QTc and treatment with concomitant medications that inhibit the cytochrome P-450 enzyme system, leading to elevated serum concentrations of medications that prolong the QT interval.
Another risk factor for patients with major psychiatric disorders is overdose of medication; 30 percent of patients with schizophrenia attempt suicide, and 10 percent of these patients succeed in the attempt; 20 to 55 percent of patients with bipolar I disorder attempt suicide, and 20 percent of these patients succeed. Other elevated risk factors are electrolyte imbalance and a history of ischemic disease.
We recommend that laboratory tests (electrolytes, kidney function, liver function, fasting glucose, cholesterol, triglycerides, calcium, and magnesium), an electrocardiogram, vital signs, and weight be obtained for all patients before they begin any antipsychotic medication and at least yearly thereafter. Changes in weight, glucose, and serum lipids associated with the use of some antipsychotic medications may also lead to problems for some patients. Nonspecific T wave changes are commonly seen in the midafternoon; therefore, obtaining ECGs before breakfast may be desirable (
+9). If the baseline QTc is 450 milliseconds or longer, alternative treatment should be prescribed whenever possible. If the QTc lengthens by 25 percent or more over baseline, the drug involved should be discontinued or the dosage reduced. If hypomagnesemia and hypokalemia are detected, they should also be corrected and closely monitored during therapy (
+4). ECGs and laboratory tests should be done at least yearly, and more frequently if risk factors are present.
Antipsychotic medications should be chosen in part on the basis of knowledge about preexisting conditions. Just as one may choose not to use ziprasidone for a patient with preexisting cardiac disease, one may choose a medication other than olanzapine or quetiapine for patients with preexisting diabetes or hyperlipidemia. Likewise, one may choose medications other than risperidone for patients with hyperprolactinemia or known sensitivity for developing extrapyramidal symptoms.
The risk of cardiac arrhythmias may be dose related, and low dosages of psychotropic medications should be used whenever possible (
+10). Because of greater cardiac sensitivity among elderly people, it is advisable to avoid low-potency neuroleptic drugs, such as thioridazine, which produce significantly more cardiac changes than high-potency agents, such as fluphenazine (
+11).
Atypical antipsychotics have largely supplanted the older, conventional agents, a change that we believe is a beneficial one. However, the notable reduction in extrapyramidal symptoms with these newer agents is not without some cost. Clinicians need to be aware of potentially serious side effects that were given little attention before the introduction of atypical antipsychotics and the concomitant reduction in extrapyramidal symptoms. Prolongation of QT intervals must be added to a growing list of side effects such as weight gain, type II diabetes, hyperlipidemia, and prolactinemia that clinicians must monitor when prescribing these medications.